Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Doctor and patient

Photo courtesy of NIH

ROME—Results of the ANTARCTIC trial suggest that monitoring platelet function to individualize antiplatelet therapy does not improve outcomes for elderly patients stented for an acute coronary syndrome.

These patients had a high risk of ischemic and bleeding complications, but the study showed no significant difference in the incidence of such complications between patients who were monitored and those who were not.

The findings challenge current international guidelines, which recommend platelet function testing in high-risk patients.

“Platelet function testing is still being used in many centers to measure the effect of antiplatelet drugs and adjust the choice of these drugs and their doses,” said study investigator Gilles Montalescot, MD, PhD, of Hôpital Pitié-Salpêtrière in Paris, France.

“Our study does not support this practice and these recommendations. Although measuring the effect of antiplatelet agents makes sense in order to choose the best

drugs or doses, this costly and more complex strategy does not appear to benefit patients, even when they present with extremely high risk of ischemic and bleeding events like those enrolled in ANTARCTIC.”

Results of the ANTARCTIC trial were presented at ESC Congress 2016 (abstract 2221) and published in The Lancet.

The study was funded by Eli Lilly and Company, Daiichi Sankyo, Stentys, Accriva Diagnostics, Medtronic, and Fondation Coeur et Recherche.

ANTARCTIC enrolled 877 patients, ages 75 and older, who presented with an acute coronary syndrome and underwent coronary stenting.

All patients were started on the antiplatelet agent prasugrel (5 mg), with 442 randomized to the conventional therapy (no adjustment) and 435 randomized to monitoring and treatment adjustment if needed.

Patients in the monitoring arm received 14 days of the daily 5 mg prasugrel dose, then underwent a platelet function test at day 14, followed by medication adjustment if the test showed high or low platelet reactivity. Additional monitoring was performed at day 28 in patients who needed treatment adjustment.

The primary endpoint of the trial was the composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, urgent revascularization, and bleeding complications at 1 year.

This endpoint occurred at a similar rate in both arms of the study—27.6% in the monitoring arm and 27.8% in the conventional therapy arm (hazard ratio=1.003; P=0.98).

Similarly, there was no significant difference between the arms with regard to the main secondary endpoint—a composite of cardiovascular death, myocardial infarction, stent thrombosis, and urgent revascularization.

This endpoint occurred in 9.9% of patients in the monitoring arm and 9.3% of patients in the conventional arm (hazard ratio=1.06; P=0.80).

“Platelet function monitoring led to a change of treatment in 44.8% of patients who were identified as being over- or under-treated, yet this strategy did not improve ischemic or safety outcomes,” Dr Montalescot noted.

“ANTARCTIC confirms the ARCTIC study in a different population with a different drug and has addressed the potential limitations of the ARCTIC study but finally reached the same conclusion. I expect there will be adjustments of guidelines and practice in light of this.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Red blood cell culture showing

Staphylococcus infection

Photo by Bill Branson

Ambulatory bloodstream infections (BSIs) can be costly in young cancer patients and recipients of hematopoietic stem cell transplants, according to research published in Pediatric Blood & Cancer.

Among the 61 patients studied, the median cost for an ambulatory BSI was $40,852, and the median length of hospital stay was 7 days.

For patients who were hospitalized for BSI and other medical issues, the cost and length of stay were much higher.

“This issue has resonance beyond the pediatric stem cell transplant and oncology patient population,” said study author Amy Billett, MD, of the Dana–Farber Cancer Institute and Boston Children’s Hospital in Massachusetts.

“At a time when many aspects of care are being shifted to the home and of heightened attention to safety and cost, this is the new frontier. What we learn about preventing outpatient bloodstream infections in these patients could have broad relevance.”

To determine the economic and hospitalization impact of ambulatory BSIs, Dr Billet and her colleagues retrospectively analyzed data on outpatient BSIs at Dana-Farber/Boston Children’s that occurred between January 1, 2012, and December 31, 2013, and resulted in hospitalization.

The team identified 74 BSIs in 61 patients. Sixty-nine percent of these infections were classified as central-line-associated bloodstream infections.

In 43% of BSIs, the patient’s central line had to be surgically removed. In 15% of cases, the child was transferred to the intensive care unit. Four patients died during hospitalization, and 3 of these deaths were associated with the infections.

Most of the hospitalizations analyzed—62—were due solely to BSIs. The remainder involved at least 1 other medical issue.

The median total cost of BSIs was $40,852, and the median length of hospital stay was 7 days.

The median cost was $36,611 among patients who were hospitalized for BSIs alone (n=62) and $89,935 for patients who were hospitalized for other medical issues as well. The median lengths of hospital stay were 6 days and 15 days, respectively.

The top 3 drivers of cost for all BSIs were room and board (43%), non-chemotherapy medications (22%), and procedures (11%).

Room and board accounted for 42% of charges among patients who were hospitalized for BSIs alone and 44% among the other patients. Non-chemotherapy medications accounted for 20% and 25%, respectively. And procedures accounted for 11% and 10%, respectively.

“Behind these metrics are real and serious risks to patients’ health,” said study author Chris Wong, MD, of Dana-Farber/Boston Children’s.

“The bottom line is that the dollar cost and lengthy hospital stays signal complications that could become life-threatening or delay treatment of the children’s cancer. Reducing these infections is important both for cost containment and quality of care.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Aedes aegypti mosquito

Photo courtesy of

Muhammad Mahdi Karim

Researchers say they have identified compounds that might be used to inhibit Zika virus replication and reduce the ability of the virus to kill brain cells.

The compounds include emricasan (a drug being investigated as a treatment to reduce liver damage from hepatitis C virus), niclosamide (a drug approved in the US to combat parasitic infections), and an investigational cyclin-dependent kinase inhibitor known as PHA-690509.

The researchers described the anti-Zika activity of these compounds in Nature Medicine.

About the virus

The Zika virus has been reported in 60 countries and territories worldwide. Currently, there are no vaccines or effective treatments for the virus.

Research and anecdotal evidence have suggested infection with the Zika virus is related to fetal microcephaly, an abnormally small head resulting from an underdeveloped and/or damaged brain. The virus has also been linked with neurological diseases such as Guillain-Barré syndrome in infected adults.

The Zika virus is spread primarily through bites from infected Aedes aegypti mosquitoes, but it can also be transmitted from mother to child, through sexual contact, via blood transfusion, and possibly through other methods.

“The Zika virus poses a global health threat,” said study author Anton Simeonov, PhD, of the National Center for Advancing Translational Sciences in Bethesda, Maryland.

“While we await the development of effective vaccines, which can take a significant amount of time, our identification of repurposed small-molecule compounds may accelerate the translational process of finding a potential therapy.”

“It takes years, if not decades, to develop a new drug,” noted study author Hongjun Song, PhD, of Johns Hopkins University School of Medicine in Baltimore, Maryland. “In this sort of global health emergency, we don’t have that kind of time.”

“So instead of using new drugs, we chose to screen existing drugs,” added Guo-li Ming, MD, PhD, also of Johns Hopkins. “In this way, we hope to create a therapy much more quickly.”

Identifying potential treatments

The researchers screened 6000 compounds, both investigational and approved (in the US), looking for drugs that might be effective against the Zika virus.

The team first exposed cell cultures to 3 strains of the virus—Ugandan, Cambodian, and Puerto Rican. Then, they introduced the various compounds and looked for indicators of cell death.

The researchers identified more than 100 promising compounds. The 3 lead compounds were emricasan, niclosamide, and PHA-690509.

These compounds were effective either in inhibiting the replication of Zika or in preventing the virus from killing brain cells. Emricasan prevents cell death, while niclosamide and PHA-690509 stop virus replication.

The researchers found that combining emricasan and PHA-690509 prevented both cell death and virus replication.

Dr Song cautioned that the 3 drugs “are very effective against Zika in the dish, but we don’t know if they can work in humans in the same way.”

For example, he noted that, although niclosamide can safely treat parasites in the human gastrointestinal tract, researchers have not yet determined if the drug can penetrate the central nervous system of adults or a fetus inside a carrier’s womb to treat the brain cells targeted by Zika.

Furthermore, it’s not clear if the drugs would address the wide range of effects of Zika infection.

“To address these questions, additional studies need to be done in animal models as well as humans to demonstrate their ability to treat Zika infection,” Dr Ming said. “So we could still be years away from finding a treatment that works.”

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Ketamine, a high-affinity, noncompetitive N-methyl-D-aspartate (NMDA)-glutamate receptor antagonist, is used in human and veterinary medicine for its anesthetic and analgesic properties.¹ NMDA receptors could trigger cellular and behavioral responses, and ketamine blocks neuronal communication pathways.

How ketamine works

Water- and lipid-soluble, ketamine is available in oral, topical, IM, and IV forms. Plasma concentrations reach maximum levels minutes after IV infusion; 5 to 15 minutes after IM administration; and 30 minutes after oral ingestion.¹ The duration of action is as long as 2 hours after IM injection, and 4 to 6 hours orally. Metabolites are eliminated in urine.

Ketamine, co-prescribed with stimulants and some antidepressant drugs, can induce unwanted effects, such as increased blood pressure. Auditory and visual hallucinations are reported occasionally, especially in patients receiving a high dosage or in those with alcohol dependence.¹ Hypertension, tachycardia, cardiac arrhythmia, and pain at injection site are the most common adverse effects.

Some advantages over ECT in treating depression

The efficacy of electroconvulsive therapy (ECT) in alleviating depression depends on seizure duration. Compared with methohexital, an anesthetic used for ECT, ketamine offers some advantages:

• increased ictal time
• augmented mid-ictal slow-wave amplitude
• shortened post-treatment re-orientation time
• less cognitive dysfunction.²

Uses for ketamine

Treatment-resistant depression. The glutamatergic system is implicated in depression.^2,3 Ketamine works in patients with treatment-resistant depression by blocking glutamate NMDA receptors and increasing the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, resulting in a rapid, sustained antidepressant effect. Response to ketamine occurs within 2 hours and lasts approximately 1 week.

Abuse potential

There is documented risk of ketamine abuse. It may create psychedelic effects that some people find pleasurable, such as sedation, disinhibition, and altered perceptions.⁶ There also may be a component of physiological dependence.⁶

Conclusion

Ketamine’s rapid antidepressant effect results could be beneficial when used in severely depressed and suicidal patients. Given the potential risks of ketamine, safety considerations will determine whether this drug is successful as a therapy for people with a mood disorder.

Further research about ketamine usage including pain management and affective disorders is anticipated.⁷ Investigations substantiating relative safety and clinical trials are still on-going.⁸

Related Resources
• Nichols SD, Bishop J. Is the evidence compelling for using ketamine to treat resistant depression? Current Psychiatry. 2015;15(5):48-51.
• National Institute of Mental Health. Highlight: ketamine: a new (and faster) path to treating depression. www.nimh.nih.gov/about/strategic-planning-reports/highlights/highlight-ketamine-a-new-and-faster-path-to-treatingdepression.shtml.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

Obesity meets 3 standard defining criteria of a disease: it is associated with impairment of normal bodily function, has characteristic signs and symptoms, and results in bodily harm.¹ Accordingly, authoritative organizations, including the American Medical Association, formally recognize obesity as a disease—more specifically, a chronic, relapsing, neurobehavioral disease.^1-6

Click here to read the activity. 

Click here to complete the posttest and evaluation.

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]

A biosimilar of etanercept received clearance for marketing from the Food and Drug Administration on Aug. 30 for all of the inflammatory disease indications held by the reference originator etanercept product, Enbrel, according to an announcement from the agency.

Approval for all of Enbrel’s indications – rheumatoid arthritis, plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and polyarticular juvenile idiopathic arthritis – was initially met with skepticism by members of the agency’s Arthritis Advisory Committee at a meeting in July because the biosimilar was compared against Enbrel in patients with plaque psoriasis only, but eventually all panel members voted to recommend approval.

The approval allows the biosimilar etanercept, called etanercept-szzs, to be marketed as a biosimilar only, not as an interchangeable product. The FDA has not yet developed guidance for manufacturers to follow to get approval for interchangeability, which means that a biosimilar “may be substituted for the reference product by a pharmacist without the intervention of the health care provider who prescribed the reference product,” according to the agency.

“We carefully evaluate the structural and functional characteristics of these complex molecules. Patients and providers can have confidence that there are no clinically meaningful differences in safety and efficacy from the reference product,” Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said in the agency’s announcement.

Etanercept-szzs will be marketed by Sandoz as Erelzi. Erelzi’s prescribing information can be found here. The biosimilar is currently undergoing review with the European Medicines Agency.

[email protected]

DURBAN, SOUTH AFRICA – HIV-infected women who remained on antiretroviral therapy throughout the postpartum period reduced their risk of clinical stage 2 or 3 HIV disease events by 53%, compared with those who stopped treatment postpartum in the PROMISE 1077HS trial, Judith Currier, MD, reported at the 21st International AIDS Conference.

PROMISE (Promoting Maternal and Infant Survival Everywhere) is an ongoing multinational, multicomponent series of clinical trials. PROMISE 1077HS was designed to assess the risks and benefits of continued antiretroviral therapy (ART), compared with stopping therapy among nonbreastfeeding women postpartum, explained Dr. Currier, professor of medicine and chief of infectious diseases at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

PROMISE 1077HS included 1,653 HIV-positive women in the United States and seven low- or middle-income countries. All participants were relatively healthy as evidenced by their median CD4+ count of 550 cells/mm³ prior to starting ART in pregnancy. None were planning to breastfeed. Upon delivery, the women were randomized to continue ART – the chief regimen was ritonavir-boosted lopinavir (Kaletra) plus tenofovir/emtricitabine (Truvada) – or stop therapy, restarting only when their CD4+ count fell below 350 cells/mm³.

Participants were prospectively followed for a median of 2.3 years post delivery. At that point, in summer 2015, the results of the landmark START trial were released (N Engl J Med. 2015 Aug 27;373[9]:795-807), paving the way for the current global strategy of ART for life in HIV-infected patients regardless of their CD4+ cell count.

The primary efficacy endpoint in PROMISE 1077HS was a composite of an AIDS event, death, or a serious cardiovascular, renal, or hepatic event. In this relatively healthy population, too few of these events occurred to allow the researchers to draw conclusions (four in the continued-ART group and six in the controls who stopped ART post partum).

But the secondary endpoint of time to World Health Organization (WHO) clinical stage 2 or 3 HIV disease events was a different story. A total of 39 of these events occurred in the continued-ART group, for a rate of 2.02% per year, compared with 80 events and a rate of 4.36% per year in controls. That difference translated into a 53% relative risk reduction. Some key WHO clinical stage 2 and 3 HIV disease events include pulmonary tuberculosis, herpes zoster, oral candidiasis, thrombocytopenia, and bacterial infection.

Fully 23% of patients in the continued-ART group had laboratory-confirmed virologic failure as defined by a viral load of HIV RNA in excess of 1,000 copies/mL after at least 24 weeks of postpartum ART. Additionally, resistance testing indicated two-thirds of affected patients showed no evidence of resistance at the time of virologic failure, meaning their viremia was due to nonadherence to ART.

“This virologic failure rate highlights the importance of the challenge of adherence in this population,” Dr. Currier said. “Interventions to improve adherence as well as studies to examine newer regimens with a high genetic barrier to resistance are needed to ensure maximal long-term benefit from this strategy of continued ART postpartum.”

The PROMISE studies are funded by the National Institutes of Health. Dr. Currier reported having no financial disclosures.

[email protected]

DURBAN, SOUTH AFRICA – HIV-infected women who remained on antiretroviral therapy throughout the postpartum period reduced their risk of clinical stage 2 or 3 HIV disease events by 53%, compared with those who stopped treatment postpartum in the PROMISE 1077HS trial, Judith Currier, MD, reported at the 21st International AIDS Conference.

PROMISE (Promoting Maternal and Infant Survival Everywhere) is an ongoing multinational, multicomponent series of clinical trials. PROMISE 1077HS was designed to assess the risks and benefits of continued antiretroviral therapy (ART), compared with stopping therapy among nonbreastfeeding women postpartum, explained Dr. Currier, professor of medicine and chief of infectious diseases at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

PROMISE 1077HS included 1,653 HIV-positive women in the United States and seven low- or middle-income countries. All participants were relatively healthy as evidenced by their median CD4+ count of 550 cells/mm³ prior to starting ART in pregnancy. None were planning to breastfeed. Upon delivery, the women were randomized to continue ART – the chief regimen was ritonavir-boosted lopinavir (Kaletra) plus tenofovir/emtricitabine (Truvada) – or stop therapy, restarting only when their CD4+ count fell below 350 cells/mm³.

Participants were prospectively followed for a median of 2.3 years post delivery. At that point, in summer 2015, the results of the landmark START trial were released (N Engl J Med. 2015 Aug 27;373[9]:795-807), paving the way for the current global strategy of ART for life in HIV-infected patients regardless of their CD4+ cell count.

The primary efficacy endpoint in PROMISE 1077HS was a composite of an AIDS event, death, or a serious cardiovascular, renal, or hepatic event. In this relatively healthy population, too few of these events occurred to allow the researchers to draw conclusions (four in the continued-ART group and six in the controls who stopped ART post partum).

But the secondary endpoint of time to World Health Organization (WHO) clinical stage 2 or 3 HIV disease events was a different story. A total of 39 of these events occurred in the continued-ART group, for a rate of 2.02% per year, compared with 80 events and a rate of 4.36% per year in controls. That difference translated into a 53% relative risk reduction. Some key WHO clinical stage 2 and 3 HIV disease events include pulmonary tuberculosis, herpes zoster, oral candidiasis, thrombocytopenia, and bacterial infection.

Fully 23% of patients in the continued-ART group had laboratory-confirmed virologic failure as defined by a viral load of HIV RNA in excess of 1,000 copies/mL after at least 24 weeks of postpartum ART. Additionally, resistance testing indicated two-thirds of affected patients showed no evidence of resistance at the time of virologic failure, meaning their viremia was due to nonadherence to ART.

“This virologic failure rate highlights the importance of the challenge of adherence in this population,” Dr. Currier said. “Interventions to improve adherence as well as studies to examine newer regimens with a high genetic barrier to resistance are needed to ensure maximal long-term benefit from this strategy of continued ART postpartum.”

The PROMISE studies are funded by the National Institutes of Health. Dr. Currier reported having no financial disclosures.

[email protected]

DURBAN, SOUTH AFRICA – HIV-infected women who remained on antiretroviral therapy throughout the postpartum period reduced their risk of clinical stage 2 or 3 HIV disease events by 53%, compared with those who stopped treatment postpartum in the PROMISE 1077HS trial, Judith Currier, MD, reported at the 21st International AIDS Conference.

PROMISE (Promoting Maternal and Infant Survival Everywhere) is an ongoing multinational, multicomponent series of clinical trials. PROMISE 1077HS was designed to assess the risks and benefits of continued antiretroviral therapy (ART), compared with stopping therapy among nonbreastfeeding women postpartum, explained Dr. Currier, professor of medicine and chief of infectious diseases at the University of California, Los Angeles.

Bruce Jancin/Frontline Medical News

PROMISE 1077HS included 1,653 HIV-positive women in the United States and seven low- or middle-income countries. All participants were relatively healthy as evidenced by their median CD4+ count of 550 cells/mm³ prior to starting ART in pregnancy. None were planning to breastfeed. Upon delivery, the women were randomized to continue ART – the chief regimen was ritonavir-boosted lopinavir (Kaletra) plus tenofovir/emtricitabine (Truvada) – or stop therapy, restarting only when their CD4+ count fell below 350 cells/mm³.

Participants were prospectively followed for a median of 2.3 years post delivery. At that point, in summer 2015, the results of the landmark START trial were released (N Engl J Med. 2015 Aug 27;373[9]:795-807), paving the way for the current global strategy of ART for life in HIV-infected patients regardless of their CD4+ cell count.

The primary efficacy endpoint in PROMISE 1077HS was a composite of an AIDS event, death, or a serious cardiovascular, renal, or hepatic event. In this relatively healthy population, too few of these events occurred to allow the researchers to draw conclusions (four in the continued-ART group and six in the controls who stopped ART post partum).

But the secondary endpoint of time to World Health Organization (WHO) clinical stage 2 or 3 HIV disease events was a different story. A total of 39 of these events occurred in the continued-ART group, for a rate of 2.02% per year, compared with 80 events and a rate of 4.36% per year in controls. That difference translated into a 53% relative risk reduction. Some key WHO clinical stage 2 and 3 HIV disease events include pulmonary tuberculosis, herpes zoster, oral candidiasis, thrombocytopenia, and bacterial infection.

Fully 23% of patients in the continued-ART group had laboratory-confirmed virologic failure as defined by a viral load of HIV RNA in excess of 1,000 copies/mL after at least 24 weeks of postpartum ART. Additionally, resistance testing indicated two-thirds of affected patients showed no evidence of resistance at the time of virologic failure, meaning their viremia was due to nonadherence to ART.

“This virologic failure rate highlights the importance of the challenge of adherence in this population,” Dr. Currier said. “Interventions to improve adherence as well as studies to examine newer regimens with a high genetic barrier to resistance are needed to ensure maximal long-term benefit from this strategy of continued ART postpartum.”

The PROMISE studies are funded by the National Institutes of Health. Dr. Currier reported having no financial disclosures.

[email protected]

[WpProQuiz 13] [WpProQuiz_toplist 13]

[WpProQuiz 13] [WpProQuiz_toplist 13]

[WpProQuiz 13] [WpProQuiz_toplist 13]

ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.

In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.

Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.

“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.

“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”

Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.

The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.

“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.

Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).

Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.

“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.

How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.

“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.

The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”

The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.

[email protected]

On Twitter @whitneymcknight

ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.

In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.

Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.

“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.

“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”

Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.

The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.

“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.

Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).

Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.

“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.

How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.

“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.

The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”

The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.

[email protected]

On Twitter @whitneymcknight

ANNAPOLIS, MD. – Women with bacterial vaginosis could soon have an effective oral, single-dose treatment option, if results of a phase III study result in approval by the Food and Drug Administration.

In a modified intention-to-treat study of 189 women with bacterial vaginosis (BV) randomly assigned 2:1 to treatment or placebo, a single, granulated oral dose of secnidazole 2g was found to be statistically superior to placebo on all clinical endpoints.

Secnidazole (SYM-1219) has a longer half-life, compared with metronidazole, the current treatment standard, according to Jane R. Schwebke, MD, the study investigator and a professor of medicine in the infectious disease department of the University of Alabama, Birmingham. Dr. Schwebke credits the study drug’s high bioavailablility and rapid absorption for its efficacy.

“You get a very high peak with SYM-1219 initially, and I think that might be the reason for the single-dose therapy’s efficacy. It’s due to the pharmacokinetics of the drug itself,” she reported at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

If the drug is approved, it would likely mean better adherence when compared with current standards of treatment, according to Sharon Hillier, PhD, director of reproductive infectious disease research at the Magee-Women’s Hospital of the University of Pittsburgh.

“It will absolutely improve compliance,” Dr. Hillier said in an interview. “Obviously, it’s much easier than taking [metronidazole] twice a day for 7 days.”

Treatment with metronidazole also requires a week of abstinence from alcohol, compared with what Dr. Hillier anticipates would be 2 or 3 days of alcohol abstinence with secnidazole.

The initial study enrollment was 189 women who were randomized 2:1 to secnidazole or placebo and treated at 21 sites nationally. After assessment for common sexually transmitted diseases, Nugent scores of 4 or greater, and all Amsel criteria (including a vaginal pH of 4.7 or greater, clue cells at or greater than 20%, and a positive KOH whiff test), 164 women remained in the modified intention-to-treat (ITT) analysis. A quarter of all women across the modified ITT group were recurrent BV sufferers, having had at least four episodes of BV in the previous year, and 87% had Nugent scores of 7 or greater.

“These were true BV cases; none were in the intermediate or mild zone,” Dr. Schwebke said.

Responders were women who, between days 21 and 30, had “normal” discharge, less than 20% clue cells, and a negative KOH whiff test. In the study arm, 53.3% of women had “normal” discharge and less than 20% clue cells at their 21-30 day visit, compared with 19.3% in the placebo group (P less than .001). The secondary endpoint – Nugent scores of 3 or less at days 7-14 – was achieved by 43.9% in the study group, compared with 5.3% of controls (P less than .001).

Just over a third of women in the study arm experienced one or more adverse events, compared with 21.9% of controls. Yeast infections were the most common adverse event. Less than 5% of the study group experienced nausea, headache, or diarrhea, compared with up to 3% of controls.

“What’s exciting about this new product is that it will be a single dose oral [that women] can take with a meal and with none of the adverse effects, and it relieves symptoms as well as other treatments,” Dr. Hillier said.

How treatment efficacy should be defined was a matter of debate during the presentation’s question and answer period. The FDA did not issue BV treatment guidance until 1998, despite prior approval of BV treatments clindamycin and metronidazole. The rigorous definition of clinical cure rate put forward in the FDA guidance document caused the cure rates that had been generally accepted by physicians to drop from as high as 80% to around 40%, according to Dr. Hilliard.

“I personally would like to see some head-to-head comparisons of the various treatments we have to know whether some are better than others,” Dr. Hillier said in the interview.

The ideal BV treatment should also provoke a microbiological cure, according to Dr. Schwebke. “What I would do is combine a drug like this with a biofilm inhibitor. Right now, this is great, because it’s single dose oral, and it’s as good as anything out there, but, I don’t think we’re taking the next step necessarily with efficacy.”

The study was supported by Symbiomix. Dr. Schwebke is a consultant for Symbiomix and receives funding from Alfa Wassermann and Starpharma, among others. Dr. Hillier is coprincipal investigator of the Microbicide Trials Network, sponsored by the National Institutes of Health.

[email protected]

On Twitter @whitneymcknight

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.

Among patients with Ewing sarcoma, functional imaging with ¹⁸fluorodeoxyglucose (FDG)–PET was a better predictor of response 9 days after the start of therapy than anatomic imaging ­modalities were at 6 weeks, results of a retrospective analysis suggest.

A study comparing the predictive ability of functional imaging modalities such as FDG-PET with that of anatomic imaging modalities such as CT or MRI showed that an early signal with FDG-PET was superior to anatomic imaging, and that newly defined tumor volume criteria were better at predicting response and clinical benefit than either World Health Organization (WHO) criteria or Response Evaluation Criteria in Solid Tumors (RECIST), reported Vadim S. Koshkin, MD, of the Cleveland Clinic and colleagues.

“The time needed to assess tumors volumetrically is slightly greater than to do so unidimensionally or bidimensionally, but the process is now automated. The analysis presented here suggests that assessment of tumor volume is superior to predict response in clinical trials, compared with the currently widely used RECIST and WHO criteria. This requires additional validation with prospective clinical trials,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.68.1858].

To get a better idea of the relative benefits of FDG-PET and anatomic imaging for assessing clinical outcomes, the investigators took a retrospective look at patients with Ewing sarcoma who were enrolled in the SARC 011 trial, a single-arm, multicenter, multicohort phase II study of patients with recurrent Ewing sarcoma treated with the investigational insulinlike growth factor–1 receptor antibody R1507.

Of the 115 patients enrolled, 76 had available anatomic imaging at baseline and at 6 weeks after the start of treatment. The imaging studies were assessed by the treating oncologist according to WHO criteria and by a central, external group of radiologists blinded to clinical outcomes of individual patients. FDG-PET studies were performed at baseline and on day 9 and were assessed by central reviewers using PET Response Criteria in Solid Tumors (PERCIST).

The authors compared PERCIST 1.0 criteria for functional imaging with FDG-PET, and for anatomic imaging, WHO and RECIST criteria were assessed independently, and newly defined volumetric criteria were based on measurements done by the central radiology group using semi-automated solid tumor segmentation software.

As noted before, the investigators found results of day 9 FDG-PET scans were associated with reduced overall survival (OS) in patients with disease progression, compared with those without progression (P = .001), and with improved OS among patients with responses to the antibody, compared with those without responses.

“There was no significance in median survival between patients who responded to treatment and patients with stable disease for any of the imaging criteria. However, for all of the criteria, there was a trend toward longer survival for patients in the response group, compared with the stable disease group,” the authors wrote.

They found that the anatomic imaging criteria (WHO local and centralized assessments, RECIST, and volume) identified fewer patients in the response group than PERCIST (FDG-PET) criteria did.

When they looked at the subgroup of 66 patients who had both interpretable functional and anatomic imaging, they found that PERCIST identified 43.9% of patients as responders, and 90.9% as nonprogressors.

The authors acknowledged that their study was hampered by the retrospective design, small sample size relative to the trial population, and lack of FDG-PET standardization to common criteria across the treatment centers.