M. Alexander Otto

Major Finding: Bardoxolone methyl improved eGFR in diabetic CKD patients by a mean of 10.1 mL/minute per 1.73 m

Data Source: Phase IIb randomized, double-blind, placebo-controlled trial enrolling 227 patients.

Disclosures: The study was funded by the drug's sponsor, Reata Pharmaceuticals. The lead investigator said he had no conflicts of interest.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved estimated glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean eGFR improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an eGFR of 20-45 mL/min per 1.73m

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

Adverse events were more common in the bardoxolone groups; 49% reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

Major Finding: Bardoxolone methyl improved eGFR in diabetic CKD patients by a mean of 10.1 mL/minute per 1.73 m

Data Source: Phase IIb randomized, double-blind, placebo-controlled trial enrolling 227 patients.

Disclosures: The study was funded by the drug's sponsor, Reata Pharmaceuticals. The lead investigator said he had no conflicts of interest.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved estimated glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean eGFR improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an eGFR of 20-45 mL/min per 1.73m

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

Adverse events were more common in the bardoxolone groups; 49% reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

Major Finding: Bardoxolone methyl improved eGFR in diabetic CKD patients by a mean of 10.1 mL/minute per 1.73 m

Data Source: Phase IIb randomized, double-blind, placebo-controlled trial enrolling 227 patients.

Disclosures: The study was funded by the drug's sponsor, Reata Pharmaceuticals. The lead investigator said he had no conflicts of interest.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved estimated glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean eGFR improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an eGFR of 20-45 mL/min per 1.73m

Their median age was 67 years, and all were on standard-of-care therapy – 98% of patients took ACE inhibitors or angiotensin-receptor blockers.

At 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorous and uric acid levels, and improved CKD stage.

Adverse events were more common in the bardoxolone groups; 49% reported muscle spasms, compared with 12% in the placebo group. The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Major Finding: Newborns in the DTaP group had substantially higher antibody concentrations than infants in the control group prior to the start of their primary DTaP series, and the differences were statistically significant.

Data Source: Prospective cohort study involving 70 women and their infants; some of the mothers received DTaP vaccine during pregnancy.

Disclosures: Dr. Hardy-Fairbanks said she had no conflicts of interest. The study was funded by Sanofi-Pasteur, maker of Daptacel DTaP vaccine.

VANCOUVER, B.C. – Infants born to women who receive diphtheria-tetanus-acellular pertussis vaccine during pregnancy have higher pertussis antibody levels during their first few months of life than infants born to unvaccinated women, Dr. Abbey Hardy-Fairbanks reported.

The levels are sufficient to protect infants against pertussis prior to their first diphtheria-tetanus-acellular pertussis (DTaP) shot at around 2 months, a period of “significant pertussis morbidity and mortality,” said Dr. Hardy-Fairbanks, an ob.gyn. at the University of Iowa, Iowa City.

“This is the first evidence to document that pertussis immunization during pregnancy is likely to be beneficial to infants when they are most vulnerable to pertussis disease.

Physicians “should consider vaccination of women during pregnancy with DTaP,” she said at the meeting.

In the prospective cohort study, 16 (23%) of 70 pregnant women received DTaP vaccine; 54 (77%) pregnant women selected as controls did not and had not been vaccinated for at least 2 years.

Four of the women (25%) in the DTaP group were vaccinated in the first trimester, eight (50%) in the second, and four (25%) in the third. Vaccination did not cause any adverse pregnancy outcomes.

Maternal blood and cord blood were collected at delivery.

Blood was also collected from children before and after their primary DTaP series and toddler booster doses at 12-18 months.

Blood samples were measured for pertussis antigens, including pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbriae, by enzyme-linked immunosorbent assay.

Newborns in the DTaP group had higher pertussis antibody concentrations than their mothers, “showing efficient placental transfer of antibodies to the infant,” Dr. Hardy-Fairbanks said.

They also had substantially higher concentrations than infants in the control group prior to the start of the primary DTaP series, and the differences were statistically significant.

However, at month 7, following completion of the DTaP series, infants born to vaccinated mothers had slightly lower antibody levels than infants in the control group.

The differences were not statistically significant, but “may represent some blunting of the infant immune response to the [vaccine],” Dr. Hardy-Fairbanks said.

By the time they got their toddler booster doses, however, antibody levels “were essentially equivalent” in the two groups, she said.

View on the News

Possible Blunted Immune Response?

Dr. Sarah Long thanked the study authors for their work. “Your findings are so very helpful. We don't have this kind of information.”

She was concerned, however, that infants born to vaccinated mothers mounted only a blunted immune response to their primary DTaP vaccine series, and wondered if responses would be blunted to other vaccines. The study's presenter said the question is currently being investigated, but so far that does not appear to be the case.

DR. LONG is the chief of the section of infectious diseases at St. Christopher's Hospital for Children in Philadelphia. She said she had no conflicts of interest.

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Mr. Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share part of the savings their efforts generate for Medicare, as long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies. The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,.”

One option is to hire a nurse to help chronically ill patients manage their diseases, Mr. Miller said. That's been proven to help reduce emergency department visits and hospitalizations,(Arch. Intern. Med. 2003;163:585–91).

The meeting's audio and transcript –as welll as public comments on ACO concerns – areonline at www.ftc.gov/opp/workshops/aco/index.shtml

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Mr. Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share part of the savings their efforts generate for Medicare, as long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies. The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,.”

One option is to hire a nurse to help chronically ill patients manage their diseases, Mr. Miller said. That's been proven to help reduce emergency department visits and hospitalizations,(Arch. Intern. Med. 2003;163:585–91).

The meeting's audio and transcript –as welll as public comments on ACO concerns – areonline at www.ftc.gov/opp/workshops/aco/index.shtml

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Mr. Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share part of the savings their efforts generate for Medicare, as long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies. The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,.”

One option is to hire a nurse to help chronically ill patients manage their diseases, Mr. Miller said. That's been proven to help reduce emergency department visits and hospitalizations,(Arch. Intern. Med. 2003;163:585–91).

The meeting's audio and transcript –as welll as public comments on ACO concerns – areonline at www.ftc.gov/opp/workshops/aco/index.shtml

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held this fall offered possible answers to both questions. Regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

Mr. Miller added that he does not believe recent election results will derail ACO efforts or other aspects of the Affordable Care Act. Despite Republican victories, “I think it would be a near impossibility to pass a repeal by a veto-proof margin. And the ACO stuff is not really controversial – yet,” he noted.

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held this fall offered possible answers to both questions. Regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

Mr. Miller added that he does not believe recent election results will derail ACO efforts or other aspects of the Affordable Care Act. Despite Republican victories, “I think it would be a near impossibility to pass a repeal by a veto-proof margin. And the ACO stuff is not really controversial – yet,” he noted.

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held this fall offered possible answers to both questions. Regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health-care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met. Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters.

Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

Mr. Miller added that he does not believe recent election results will derail ACO efforts or other aspects of the Affordable Care Act. Despite Republican victories, “I think it would be a near impossibility to pass a repeal by a veto-proof margin. And the ACO stuff is not really controversial – yet,” he noted.

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met.

Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters. Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,” he said.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

The meeting's audio and transcript – as well as public comments on ACO concerns – are online at www.ftc.gov/opp/workshops/aco/index.shtml

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met.

Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters. Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,” he said.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

The meeting's audio and transcript – as well as public comments on ACO concerns – are online at www.ftc.gov/opp/workshops/aco/index.shtml

Many physicians have wondered how – and even if – they will be able to work together to form accountable care organizations without violating federal antitrust and fraud and abuse laws.

A federal regulatory meeting held earlier this fall offered possible answers to both questions. Federal regulators are considering exemptions to those laws that would allow providers who meet certain requirements to form ACOs.

“It is not easy to craft safe harbors that can replace an antitrust review that analyzes the specific facts of each case and market. But we're going to try to do this,” said Jon Leibowitz, chairman of the Federal Trade Commission (FTC).

Similarly, Daniel Levinson, inspector general of the U.S. Department of Health and Human Services, noted that the Affordable Care Act gives the HHS secretary the authority to waive some fraud and abuse laws as needed to help ACO programs develop.

“We and our HHS colleagues are looking closely at how the secretary might exercise this authority most effectively,” Levinson said, according to the meeting transcript.

The FTC, the HHS Office of Inspector General, and the Centers for Medicare and Medicaid Services conducted the workshop in Baltimore to hear the opinions of panelists and audience members on a variety of ACO issues.

However, much of the questioning focused on how antitrust and fraud and abuse exemptions could be applied to ACOs.

The Affordable Care Act promotes ACO creation to reduce health care fragmentation, improve outcomes, and cut health spending by, for instance, keeping patients out of hospitals when possible.

The goal is for providers to come together and contract with the CMS to integrate and manage the care of at least 5,000 patients, and to share a portion of the savings their efforts generate for Medicare, so long as quality parameters are met.

Once formed, ACOs could pursue similar types of contracts with commercial insurance companies.

The catch is that encouraging independent providers to jointly negotiate contracts and payment rates with health plans raises concerns about joint price fixing, reduced competition, and other antitrust matters. Likewise, the shared-savings provision, among others, raises antikickback, self-referral, and other fraud and abuse concerns, according to health care attorney Douglas Hastings, board chair of Epstein Becker & Green, Washington, and a meeting panelist who offered his insights during a later interview.

Regulators are interested in applying to ACOs antitrust protections that already exist for providers who are clinically integrated and jointly accept significant financial risk.

“In those cases, [collaboration is] not viewed as an antitrust matter, since they are behaving as an integrated organization,” explained meeting panelist and health policy expert Harold Miller, executive director of the Center for Health Care Quality and Payment Reform, who also offered his insights during a later interview.

Defining the extent of integration required for protection, and the time frame to achieve it, remain key issues for regulators, as does the possible creation of additional antitrust safe harbors related to market share and other matters. Regulators also said that they want to foster multiple ACOs in a given market to increase competition.

Which providers would be covered under fraud and abuse waivers also remains an issue, as well as whether waivers should apply only to shared savings payments or to other financial relationships ACOs create, Troy Barsky, director of the CMS Division of Technical Payment Policy, explained during the meeting.

Overall, the hope is to spur “coordination [and] cooperation among the people and the entities that provide health care,” while at the same time ensure “appropriate corporate behaviors,” said Dr. Donald Berwick, CMS Administrator.

Proposed ACO regulations are expected from the CMS in late December.

In the meantime, Mr. Miller advised physicians, “If you want to be an ACO, you have to start looking at the data you have – or get access to data from payers, Medicare, and others – to identify opportunities for savings. Once you know where they are, figure out what programs to put in place to achieve those savings,” he said.

To make such programs cost effective, however, “a small practice will need to think about how to partner with other practices in order to have enough patients who can benefit,” he said.

The meeting's audio and transcript – as well as public comments on ACO concerns – are online at www.ftc.gov/opp/workshops/aco/index.shtml

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

DENVER — A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug's maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The “trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events,” in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the meeting.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the clinical trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group.

That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, noted Dr. Baigent.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. “With full compliance, we would be likely to reduce the risk of vascular events by about a quarter,” he predicted.

However, lowering patients' LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that “it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death,” and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent.

As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

Dr. Baigent said he has no conflicts of interest. Dr. Baigent said that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER — A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug's maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The “trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events,” in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the meeting.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the clinical trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group.

That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, noted Dr. Baigent.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. “With full compliance, we would be likely to reduce the risk of vascular events by about a quarter,” he predicted.

However, lowering patients' LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that “it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death,” and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent.

As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

Dr. Baigent said he has no conflicts of interest. Dr. Baigent said that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

DENVER — A once-daily combination of ezetimibe 10 mg and simvastatin 20 mg reduced the risk of major atherosclerotic events in patients with chronic kidney disease by 16.5%, according to a randomized, placebo-controlled trial funded by the drug's maker, Merck.

However, the combination (trade name Vytorin) did not slow progression to end-stage renal disease in the trial or significantly impact mortality.

The “trial results provide clear evidence that lowering cholesterol with [Vytorin] reduces the risk of major atherosclerotic events,” in patients with chronic kidney disease, said Dr. Colin Baigent, Oxford University professor of epidemiology, and the lead investigator of the Study of Heart and Renal Protection (SHARP) trial. He presented the study results at the meeting.

Merck will seek Food and Drug Administration approval for Vytorin use in CKD patients based on the SHARP trial results, the company said.

In SHARP, 4,650 patients with chronic kidney disease were randomized to Vytorin, and 4,620 to placebo. The median duration of therapy was 4.9 years. The mean age at baseline was 62 years, and patients had no revascularization or myocardial infarction histories. A total of 23% had diabetes, and 15% had vascular disease.

About a third of the patients started the clinical trial on dialysis; the remainder had a baseline average estimated glomerular filtration rate of 26.5 mL/minute per 1.73 m

The average LDL cholesterol at enrollment was 108 mg/dL. Midway through the trial, Vytorin lowered LDL cholesterol by an average of 32 mg/dL.

Major atherosclerotic events – coronary death, myocardial infarction, nonhemorrhagic stroke, or revascularization – occurred in 11.3% (526) of patients in the Vytorin group, and in 13.4% (619) of patients in the placebo group.

That translated to a significant 16.5% risk reduction among Vytorin users, results similar to previous statin studies in other populations, noted Dr. Baigent.

The rate of treatment compliance was about two-thirds among patients in both the placebo and Vytorin arms of the trial. “With full compliance, we would be likely to reduce the risk of vascular events by about a quarter,” he predicted.

However, lowering patients' LDL did not affect progression to end-stage renal disease, which developed in about a third of patients in each arm: 33.9% of the treatment group, and 34.6% of the control group.

Cancer was also on the minds of investigators during the trial, due to reports about possible carcinogenicity associated with use of ezetimibe (trade name Zetia).

The Food and Drug Administration concluded in December 2009 that “it is unlikely that Vytorin or Zetia increases the risk of cancer or cancer-related death,” and the SHARP results supported the assertion.

There were 438 cancers diagnosed and 150 cancer deaths in the Vytorin group, compared with 439 cancers diagnosed and 128 cancer deaths in the placebo group. The mortality difference was not significant.

Overall, cardiac, renal, and vascular-related deaths were less frequent in Vytorin users, but nonvascular deaths were more frequent.

As with cancer deaths, however, the differences between the groups were small and not significant.

Similarly, there were no significant differences in myopathy, rhabdomyolysis, liver dysfunction, pancreatitis, or gallstone complications between the two groups.

Dr. Baigent said he has no conflicts of interest. Dr. Baigent said that the trial was run independently of Merck, and that he and his colleagues do not accept payments from the pharmaceutical industry, other than the costs of attending scientific meetings.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

A 24-week course of bardoxolone methyl, an experimental antioxidant inflammation modulator, improved glomerular filtration rates in chronic kidney disease patients with type 2 diabetes, according to a randomized phase IIb study funded by the drug's sponsor, Reata Pharmaceuticals Inc.

A phase III study slated to start next year will test whether the mean improvement of 10.1 mL/minute per 1.73 m

“You want to make sure this drug will be associated with a clinical outcome,” said Dr. Pergola, the lead investigator of the phase IIb study.

Patients in the randomized, double-blind, placebo-controlled trial were assigned to 25-mg, 75-mg, or 150-mg daily doses of bardoxolone or to placebo. Each group had 57 subjects, except the 150-mg group, which had 56.

In addition to type 2 diabetes, subjects had stage 3b or 4 chronic kidney disease (CKD), with an estimated glomerular filtration rate (eGFR) of 20-45 mL/minute per 1.73m

At the end of 24 weeks, bardoxolone patients had a mean eGFR gain of 10.1 mL/minute per 1.73 m

About 73% (124) of patients in each bardoxolone group had at least a 10% eGFR increase; approximately 25% (43) had more than a 50% increase.

Increased eGFRs also correlated with decreased blood-urea-nitrogen levels, decreased serum phosphorus and uric acid levels, and improved CKD stage.

“The maximal effect seems to be at 75 mg,” Dr. Pergola said, with smaller eGFR gains at 25 mg and no greater gains at 150 mg.

Adverse events were more common in the bardoxolone groups; 49% of bardoxolone patients reported muscle spasms, compared with 12% in the placebo group.

The spasms were thought to be treatment related, as were nausea, hypomagnesemia, and diminished appetite.

The muscle cramps led to slightly higher discontinuation rates in bardoxolone subjects, Dr. Pergola said. But “the [spasms] seem to be transient and, importantly, there is no increase in biochemical markers of muscle damage.”

Reata plans to release 52-week outcomes early next year.

Dr. Pergola said he has no disclosures.

VANCOUVER, B.C. — A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient's resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

“Why do it? Because it works,” said Dr. Bakken, an infectious disease specialist at St. Luke's Hospital in Duluth, Minn.

“It's a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It's safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours,” he said.

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation's merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

“This is 2010, not 1910. We can do better than fecal transplantation,” Dr. Gerding said.

Even so, there is “no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials,” he said.

“The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff,” Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It's less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis. Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients. “Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse,” Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. — A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient's resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

“Why do it? Because it works,” said Dr. Bakken, an infectious disease specialist at St. Luke's Hospital in Duluth, Minn.

“It's a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It's safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours,” he said.

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation's merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

“This is 2010, not 1910. We can do better than fecal transplantation,” Dr. Gerding said.

Even so, there is “no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials,” he said.

“The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff,” Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It's less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis. Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients. “Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse,” Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

VANCOUVER, B.C. — A decades-old technique – fecal transplantation – cures more than 90% of C. difficile patients who relapse after antibiotic therapy, as up to a third do, according to Dr. Johan Bakken.

In fecal transplantation, donor stool is delivered from below through a colonoscope or retention enema, or from above through a nasogastric or nasoduodenal tube, to replace colonic flora wiped out by antibiotics, reestablishing the patient's resistance to colonization by C. difficile.

To date, at least 159 cases have been reported in the literature, dating back to 1958. Cure rates in case series range from 50% to 100%, with most toward the higher end of the scale, and an overall success rate of 91% (Euro. Surveill. 2009;14:19316).

“Why do it? Because it works,” said Dr. Bakken, an infectious disease specialist at St. Luke's Hospital in Duluth, Minn.

“It's a simple and logical replacement therapy that works when antibiotic therapy fails, with a greater than 90% success rate. It's safe, inexpensive, reimbursable, quick, and easy to perform. The first bowel movement afterward is normal within 24 hours,” he said.

In one case series, patients reported rapid resolution of abdominal pain, normalization of stool frequency and consistency, and an increased sense of well-being within 24-48 hours (Clin. Infect. Dis. 2003;36:580-5).

A randomized trial is currently underway in the Netherlands pitting vancomycin therapy against nasoduodenal tube fecal transplantation for recurrent C. difficile infections (Euro. Surveill. 2009;14:19316).

Dr. Bakken made his comments during a debate about fecal transplantation's merits with Dr. Dale N. Gerding, professor of medicine at Loyola University, Chicago.

Tapered, pulsed, and intermittent vancomycin are other options, though success varies, Dr. Gerding said.

Researchers are also working on antibiotics less punishing to healthy gut flora than vancomycin, synthetic stool preparations to avoid the use of donor stool, nontoxigenic C. difficile to outcolonize toxic strains, and vaccines and antibodies to bolster immune responses to the pathogen.

“This is 2010, not 1910. We can do better than fecal transplantation,” Dr. Gerding said.

Even so, there is “no question that [fecal transplantation] results are impressive even without controlled, randomized, and blinded trials,” he said.

“The cost of goods is low, unlikely to be in short supply, and unlikely to be addictive. It is obvious that feces have the right stuff,” Dr. Gerding said.

Dr. Bakken recently published a review of the fecal transplantation literature and described his technique for the procedure (Anaerobe 2009;15:285-9). His medical group in Duluth has performed transplants in more than 80 patients, he said.

Although donor stool was delivered through a colonoscope or retention enema in about three-quarters of published cases, Dr. Bakken prefers the nasogastric tube for instillation.

It's less messy and guarantees delivery of bacteria to the entire gut, and one instillation is usually enough. Far less donor stool is needed, as well; up to 200 g of donor stool must be delivered from below, and often more than once.

A 4-day course of vancomycin is usually given before instillation to reduce the burden of vegetative C. difficile colonies; 20 mg of oral omeprazole are given the evening before and the morning of the procedure to cut stomach acid and create a receptive environment for instilled bacteria.

Although there have been no reports of contagions passed through donor stool, donors are screened for hepatitis A, B, and C viruses, as well as HIV, cytomegalovirus, Epstein-Barr virus, human T-lymphotropic virus, and syphilis. Dr. Bakken said he also screens donor stool for C. difficile toxin, ova, and parasites, and cultures it for enteric bacterial pathogens.

As an added precaution, a spouse donor is preferred; daily contact means spouses likely already share gut flora with patients. “Severe [C. difficile infection] represents the single situation when you should be willing to take crap from your spouse,” Dr. Bakken joked.

Dr. Bakken disclosed he is a nonsalaried consultant to Cobax Biopharma, which is developing a synthetic stool product. Dr. Gerding disclosed he holds patents for the treatment and prevention of C. difficile infection licensed to ViroPharma, and is a consultant for the company, as well as several others, including Astellas, Cubist, Merck & Co., Pfizer, and Schering-Plough. He also holds research grants from Eurofins Medinet, GOJO, Merck, Optimer, Sanofi Pasteur, and ViroPharma.

Major Finding: A score based on age, temperature, leukocytosis, albumin, and systemic antibiotic use correlates with cure rates in C. difficile infection with a P value of less than .001.

Data Source: ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. ATLAS scores for 516 patients with CDI were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

Disclosures: Dr. Miller is a scientific adviser and grant investigator to several pharmaceutical companies, including Merck & Co., Novartis Pharmaceuticals, and Optimer Pharmaceuticals.

VANCOUVER, B.C. — A simple scoring of five bedside assessments when Clostridium difficile infection is first diagnosed correlates significantly with cure rate.

“The higher the score, the lower the cure rate,” said Dr. Mark Miller, head of the division of infectious diseases and chief of the department of microbiology at SMBD–Jewish General Hospital, McGill University, Montreal, who presented the findings.

The five parameters are age, temperature, leukocytosis, albumin, and systemic concomitant antibiotic use, ATLAS for short. The first four are rated on a 0-2 scale; 2 is added to the score if the patient is on systemic antibiotics, 0 if not. ATLAS scores range from 0 to 10. (See box at right.)

The score also correlates with recurrence, but the correlation is not statistically significant.

Dr. Miller said there is a need to be able to categorize patients by C. difficile infection (CDI) severity to determine who should be treated aggressively, assign and assess outcomes in clinical studies, and communicate with other medical workers.

“If someone calls up and says 'I have a case of moderate CDI,' it's pretty much left up to the imagination about what they are talking about,” at present, he said.

Although much work has been done previously to create a prognostic system for CDI, proposed systems have not been adequately validated, Dr. Miller said.

However, “if you look at all these publications, it's all the same risk factors,” he added.

So Dr. Miller and his colleagues combined them. “What we came up with was a simple combination of the bedside risk factors that are easy to collect and, we feel, should be most associated with cure and recurrence.”

C. difficile strain type was omitted because it's not usually known at the time of diagnosis; baseline serum creatinine isn't either, so its elevation above baseline also was excluded.

ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. The ATLAS scores of 516 patients were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

There was “an excellent correlation with cure rate,” Dr. Miller said. (R

Patients with an ATLAS score of 0 had a 98% cure rate; the rate dropped incrementally with higher scores. ATLAS scores of 7 corresponded to a 55% cure rate.

Dr. Miller and his colleagues then checked the 450 subjects cured after treatment to see who had gotten another C. difficile infection.

“With recurrence, the ATLAS score didn't fair quite so well,” he said.

Recurrence rates climbed with higher scores; 11% of patients with a 0 score had a recurrence, 43% with a score of 6.

But the correlation was weak (R

A subgroup analysis found that 229 patients assigned to the vancomycin arm threw the recurrence results off (R

Recurrence rates in the vancomycin arm were much higher, not neatly distributed along a curve, which might have thrown off the results, Dr. Miller said.

Perhaps, there may also “be some additional refinement of the systemic antibiotics score that would improve” ATLAS's correlation with recurrence, he said.

A second study presented in Vancouver showed significant correlation between ATLAS scores and 30-day CDI mortality in 308 adults aged 60 years or older.

“ATLAS score appears to … predict severity in CDI in our patient population,” according to the abstract, of which Dr. Miller was a coauthor.

Vitals

Source Elsevier Global Medical News

Major Finding: A score based on age, temperature, leukocytosis, albumin, and systemic antibiotic use correlates with cure rates in C. difficile infection with a P value of less than .001.

Data Source: ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. ATLAS scores for 516 patients with CDI were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

Disclosures: Dr. Miller is a scientific adviser and grant investigator to several pharmaceutical companies, including Merck & Co., Novartis Pharmaceuticals, and Optimer Pharmaceuticals.

VANCOUVER, B.C. — A simple scoring of five bedside assessments when Clostridium difficile infection is first diagnosed correlates significantly with cure rate.

“The higher the score, the lower the cure rate,” said Dr. Mark Miller, head of the division of infectious diseases and chief of the department of microbiology at SMBD–Jewish General Hospital, McGill University, Montreal, who presented the findings.

The five parameters are age, temperature, leukocytosis, albumin, and systemic concomitant antibiotic use, ATLAS for short. The first four are rated on a 0-2 scale; 2 is added to the score if the patient is on systemic antibiotics, 0 if not. ATLAS scores range from 0 to 10. (See box at right.)

The score also correlates with recurrence, but the correlation is not statistically significant.

Dr. Miller said there is a need to be able to categorize patients by C. difficile infection (CDI) severity to determine who should be treated aggressively, assign and assess outcomes in clinical studies, and communicate with other medical workers.

“If someone calls up and says 'I have a case of moderate CDI,' it's pretty much left up to the imagination about what they are talking about,” at present, he said.

Although much work has been done previously to create a prognostic system for CDI, proposed systems have not been adequately validated, Dr. Miller said.

However, “if you look at all these publications, it's all the same risk factors,” he added.

So Dr. Miller and his colleagues combined them. “What we came up with was a simple combination of the bedside risk factors that are easy to collect and, we feel, should be most associated with cure and recurrence.”

C. difficile strain type was omitted because it's not usually known at the time of diagnosis; baseline serum creatinine isn't either, so its elevation above baseline also was excluded.

ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. The ATLAS scores of 516 patients were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

There was “an excellent correlation with cure rate,” Dr. Miller said. (R

Patients with an ATLAS score of 0 had a 98% cure rate; the rate dropped incrementally with higher scores. ATLAS scores of 7 corresponded to a 55% cure rate.

Dr. Miller and his colleagues then checked the 450 subjects cured after treatment to see who had gotten another C. difficile infection.

“With recurrence, the ATLAS score didn't fair quite so well,” he said.

Recurrence rates climbed with higher scores; 11% of patients with a 0 score had a recurrence, 43% with a score of 6.

But the correlation was weak (R

A subgroup analysis found that 229 patients assigned to the vancomycin arm threw the recurrence results off (R

Recurrence rates in the vancomycin arm were much higher, not neatly distributed along a curve, which might have thrown off the results, Dr. Miller said.

Perhaps, there may also “be some additional refinement of the systemic antibiotics score that would improve” ATLAS's correlation with recurrence, he said.

A second study presented in Vancouver showed significant correlation between ATLAS scores and 30-day CDI mortality in 308 adults aged 60 years or older.

“ATLAS score appears to … predict severity in CDI in our patient population,” according to the abstract, of which Dr. Miller was a coauthor.

Vitals

Source Elsevier Global Medical News

Major Finding: A score based on age, temperature, leukocytosis, albumin, and systemic antibiotic use correlates with cure rates in C. difficile infection with a P value of less than .001.

Data Source: ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. ATLAS scores for 516 patients with CDI were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

Disclosures: Dr. Miller is a scientific adviser and grant investigator to several pharmaceutical companies, including Merck & Co., Novartis Pharmaceuticals, and Optimer Pharmaceuticals.

VANCOUVER, B.C. — A simple scoring of five bedside assessments when Clostridium difficile infection is first diagnosed correlates significantly with cure rate.

“The higher the score, the lower the cure rate,” said Dr. Mark Miller, head of the division of infectious diseases and chief of the department of microbiology at SMBD–Jewish General Hospital, McGill University, Montreal, who presented the findings.

The five parameters are age, temperature, leukocytosis, albumin, and systemic concomitant antibiotic use, ATLAS for short. The first four are rated on a 0-2 scale; 2 is added to the score if the patient is on systemic antibiotics, 0 if not. ATLAS scores range from 0 to 10. (See box at right.)

The score also correlates with recurrence, but the correlation is not statistically significant.

Dr. Miller said there is a need to be able to categorize patients by C. difficile infection (CDI) severity to determine who should be treated aggressively, assign and assess outcomes in clinical studies, and communicate with other medical workers.

“If someone calls up and says 'I have a case of moderate CDI,' it's pretty much left up to the imagination about what they are talking about,” at present, he said.

Although much work has been done previously to create a prognostic system for CDI, proposed systems have not been adequately validated, Dr. Miller said.

However, “if you look at all these publications, it's all the same risk factors,” he added.

So Dr. Miller and his colleagues combined them. “What we came up with was a simple combination of the bedside risk factors that are easy to collect and, we feel, should be most associated with cure and recurrence.”

C. difficile strain type was omitted because it's not usually known at the time of diagnosis; baseline serum creatinine isn't either, so its elevation above baseline also was excluded.

ATLAS was tested using patient data from a large North American trial comparing fidaxomicin to vancomycin for CDI. The ATLAS scores of 516 patients were calculated at their time of diagnosis and matched against their cure rates following 10 days of study treatment.

There was “an excellent correlation with cure rate,” Dr. Miller said. (R

Patients with an ATLAS score of 0 had a 98% cure rate; the rate dropped incrementally with higher scores. ATLAS scores of 7 corresponded to a 55% cure rate.

Dr. Miller and his colleagues then checked the 450 subjects cured after treatment to see who had gotten another C. difficile infection.

“With recurrence, the ATLAS score didn't fair quite so well,” he said.

Recurrence rates climbed with higher scores; 11% of patients with a 0 score had a recurrence, 43% with a score of 6.

But the correlation was weak (R

A subgroup analysis found that 229 patients assigned to the vancomycin arm threw the recurrence results off (R

Recurrence rates in the vancomycin arm were much higher, not neatly distributed along a curve, which might have thrown off the results, Dr. Miller said.

Perhaps, there may also “be some additional refinement of the systemic antibiotics score that would improve” ATLAS's correlation with recurrence, he said.

A second study presented in Vancouver showed significant correlation between ATLAS scores and 30-day CDI mortality in 308 adults aged 60 years or older.

“ATLAS score appears to … predict severity in CDI in our patient population,” according to the abstract, of which Dr. Miller was a coauthor.

Vitals

Source Elsevier Global Medical News