Clinical question: Is there a benefit to home noninvasive ventilation (NIV) following a hospital admission for chronic obstructive pulmonary disease (COPD) exacerbation?

Background: Preventing hospital readmission following a COPD exacerbation is a priority; however, the role of NIV in this situation remains uncertain.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Clinical question: Is there a benefit to home noninvasive ventilation (NIV) following a hospital admission for chronic obstructive pulmonary disease (COPD) exacerbation?

Background: Preventing hospital readmission following a COPD exacerbation is a priority; however, the role of NIV in this situation remains uncertain.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Clinical question: Is there a benefit to home noninvasive ventilation (NIV) following a hospital admission for chronic obstructive pulmonary disease (COPD) exacerbation?

Background: Preventing hospital readmission following a COPD exacerbation is a priority; however, the role of NIV in this situation remains uncertain.

Dr. Herscher is assistant professor, division of hospital medicine, Icahn School of Medicine of the Mount Sinai Health System.

Tension pneumoperitoneum (TPP), also known as hyperacute abdominal compartment syndrome or abdominal tamponade, is a rare condition most commonly associated with gastrointestinal (GI) perforation during endoscopy and iatrogenic insufflation of gas into the peritoneal cavity.¹ Other reported causes of TPP include gastric rupture after cardiopulmonary resuscitation, barotrauma during scuba diving, positive pressure ventilation through pleural-peritoneal channels, and spontaneous TPP of uncertain mechanism.^1-4

Case Presentation

A 76-year-old male with a history of ischemic cardiomyopathy, hypertension, and diabetes mellitus presented to the VA Puget Sound Health Care System in Seattle, Washington emergency department with painless jaundice, hematemesis, melena, and acute renal failure. On esophagogastroduodenoscopy (EGD), he was found to have an ulcer on the posterior wall of the duodenal bulb. The ulcer was coagulated and injected with epinephrine. The patient’s subsequent hospital course was complicated by worsening liver function, the need for renal replacement therapy, and recurrence of upper GI bleeding that required a transcatheter embolization of 2 separate superior pancreaticoduodenal arteries (SPDA) and the inferior pancreaticoduodenal artery (IPDA).

Once clinically stable, an endoscopic retrograde cholangiopancreatography (ERCP) was performed to evaluate for cholangiocarcinoma. A stricture was discovered in the common hepatic duct, brushings were taken, and a 15 cm, 7 Fr stent was placed in the common hepatic duct. The procedure was performed with an Olympus TJF Type Q180V duodenovideoscope (Tokyo, Japan) with an external diameter of 13.7 mm. The patient became hypotensive during the procedure and was treated with phenylephrine and ephedrine boluses. There was no endoscopic evidence of bleeding or bowel trauma.

After completion of the procedure, in the recovery area the patient became severely hypotensive and unresponsive. The physical examination was noteworthy for gross abdominal distention. Arterial blood gas analysis revealed severe metabolic and respiratory acidosis. Chest radiography demonstrated massive pneumoperitoneum, low lung volumes, and diaphragmatic compression (Figure).

Discussion

In relation to upper GI endoscopic procedures, TPP has been reported after diagnostic EGD, endoscopic sphincterotomy, and submucosal tumor dissection.^5-7 During these interventions, clinically apparent or overt iatrogenic perforations can occur either in the stomach or duodenum. These perforations may function as one-way valves that cause massive air accumulation and marked elevation of the diaphragm, which severely decreases lung volumes, pulmonary compliance, and limits gas exchange. Hemodynamically, compression of the inferior vena cava restricts venous return to the heart, resulting in decreased cardiac output.⁸

Patients with TPP present in acute distress with dyspnea, abdominal pain, and shock. On physical examination the abdomen is markedly distended, tympanic, and rigid. Rectal prolapse and subcutaneous emphysema also may be present.⁹ Roentographic features of TPP include findings of intraperitoneal air with elevation of the diaphragm, medial displacement of the liver (saddlebag sign), and juxtaposition of air in visceral interfaces, making intra-abdominal structures (spleen and gallbladder) appear more discrete.¹⁰ Abdominal computer tomography may show massive pneumoperitoneum with bowel loop compression and centralization of abdominal organs.⁴

Treatment strategies include emergent decompression either with percutaneous catheter insertion or abdominal drain placement followed by a definitive surgical repair. As with management of tension pneumothorax, treatment should not be delayed while awaiting confirmatory radiologic studies.⁹ When percutaneous needle decompression is undertaken, it is preferable to use a large bore (14-gauge venous catheter) and to advance a catheter over a needle to minimize the risk of visceral injury with egress of air and return of abdominal organs to their normal anatomical positions. The needle should be inserted directly above or below the umbilicus or in the left or right lower quadrants to avoid solid organ (ie, liver or spleen) injury.

Etiologic possibilities for the duodenal perforation in this case include mechanical trauma from the endoscope and duodenal tissue infarction after embolization of a bleeding duodenal ulcer. The duodenum and pancreatic head have a dual blood supply from the SPDA, a branch of the gastroduodenal artery, and the IPDA, a branch of the superior mesenteric artery.¹¹ After failed endoscopic management of persistent duodenal hemorrhage, the patient underwent synchronous embolization of 2 separate SPDAs and the IPDA. This might have put the first 2 segments of the duodenum at risk for ischemic damage and caused it to perforate at some point during the patient’s hospitalization (as evidenced by the bilious ascitis) or rendered them vulnerable to perforation from intraluminal insufflation during endoscopy.¹²

During the laparotomy, a pinhole-sized perforation was noted in the anterior wall of the second part of the duodenum, distinct form the duodenal ulcer present on the posterior wall. This perforation likely provided a pathway for the intraluminal gas to escape into the peritoneal cavity, culminating in abdominal tamponade, cardiopulmonary deterioration, and arrest. Needle decompression of the abdominal cavity provided an effective, though temporizing relief of this pressure, enabling return of spontaneous circulation.

This case highlights the need for a high index of suspicion for TPP in a patient with cardiopulmonary compromise and abdominal distension after upper GI endoscopic procedures even in the absence of identifiable perforations. Close coordination among gastroenterologists, anesthesiologists, and surgeons is key in prevention, recognition, and management of this rare but catastrophic complication.

Tension pneumoperitoneum (TPP), also known as hyperacute abdominal compartment syndrome or abdominal tamponade, is a rare condition most commonly associated with gastrointestinal (GI) perforation during endoscopy and iatrogenic insufflation of gas into the peritoneal cavity.¹ Other reported causes of TPP include gastric rupture after cardiopulmonary resuscitation, barotrauma during scuba diving, positive pressure ventilation through pleural-peritoneal channels, and spontaneous TPP of uncertain mechanism.^1-4

Case Presentation

A 76-year-old male with a history of ischemic cardiomyopathy, hypertension, and diabetes mellitus presented to the VA Puget Sound Health Care System in Seattle, Washington emergency department with painless jaundice, hematemesis, melena, and acute renal failure. On esophagogastroduodenoscopy (EGD), he was found to have an ulcer on the posterior wall of the duodenal bulb. The ulcer was coagulated and injected with epinephrine. The patient’s subsequent hospital course was complicated by worsening liver function, the need for renal replacement therapy, and recurrence of upper GI bleeding that required a transcatheter embolization of 2 separate superior pancreaticoduodenal arteries (SPDA) and the inferior pancreaticoduodenal artery (IPDA).

Once clinically stable, an endoscopic retrograde cholangiopancreatography (ERCP) was performed to evaluate for cholangiocarcinoma. A stricture was discovered in the common hepatic duct, brushings were taken, and a 15 cm, 7 Fr stent was placed in the common hepatic duct. The procedure was performed with an Olympus TJF Type Q180V duodenovideoscope (Tokyo, Japan) with an external diameter of 13.7 mm. The patient became hypotensive during the procedure and was treated with phenylephrine and ephedrine boluses. There was no endoscopic evidence of bleeding or bowel trauma.

After completion of the procedure, in the recovery area the patient became severely hypotensive and unresponsive. The physical examination was noteworthy for gross abdominal distention. Arterial blood gas analysis revealed severe metabolic and respiratory acidosis. Chest radiography demonstrated massive pneumoperitoneum, low lung volumes, and diaphragmatic compression (Figure).

Discussion

In relation to upper GI endoscopic procedures, TPP has been reported after diagnostic EGD, endoscopic sphincterotomy, and submucosal tumor dissection.^5-7 During these interventions, clinically apparent or overt iatrogenic perforations can occur either in the stomach or duodenum. These perforations may function as one-way valves that cause massive air accumulation and marked elevation of the diaphragm, which severely decreases lung volumes, pulmonary compliance, and limits gas exchange. Hemodynamically, compression of the inferior vena cava restricts venous return to the heart, resulting in decreased cardiac output.⁸

Patients with TPP present in acute distress with dyspnea, abdominal pain, and shock. On physical examination the abdomen is markedly distended, tympanic, and rigid. Rectal prolapse and subcutaneous emphysema also may be present.⁹ Roentographic features of TPP include findings of intraperitoneal air with elevation of the diaphragm, medial displacement of the liver (saddlebag sign), and juxtaposition of air in visceral interfaces, making intra-abdominal structures (spleen and gallbladder) appear more discrete.¹⁰ Abdominal computer tomography may show massive pneumoperitoneum with bowel loop compression and centralization of abdominal organs.⁴

Treatment strategies include emergent decompression either with percutaneous catheter insertion or abdominal drain placement followed by a definitive surgical repair. As with management of tension pneumothorax, treatment should not be delayed while awaiting confirmatory radiologic studies.⁹ When percutaneous needle decompression is undertaken, it is preferable to use a large bore (14-gauge venous catheter) and to advance a catheter over a needle to minimize the risk of visceral injury with egress of air and return of abdominal organs to their normal anatomical positions. The needle should be inserted directly above or below the umbilicus or in the left or right lower quadrants to avoid solid organ (ie, liver or spleen) injury.

Etiologic possibilities for the duodenal perforation in this case include mechanical trauma from the endoscope and duodenal tissue infarction after embolization of a bleeding duodenal ulcer. The duodenum and pancreatic head have a dual blood supply from the SPDA, a branch of the gastroduodenal artery, and the IPDA, a branch of the superior mesenteric artery.¹¹ After failed endoscopic management of persistent duodenal hemorrhage, the patient underwent synchronous embolization of 2 separate SPDAs and the IPDA. This might have put the first 2 segments of the duodenum at risk for ischemic damage and caused it to perforate at some point during the patient’s hospitalization (as evidenced by the bilious ascitis) or rendered them vulnerable to perforation from intraluminal insufflation during endoscopy.¹²

During the laparotomy, a pinhole-sized perforation was noted in the anterior wall of the second part of the duodenum, distinct form the duodenal ulcer present on the posterior wall. This perforation likely provided a pathway for the intraluminal gas to escape into the peritoneal cavity, culminating in abdominal tamponade, cardiopulmonary deterioration, and arrest. Needle decompression of the abdominal cavity provided an effective, though temporizing relief of this pressure, enabling return of spontaneous circulation.

This case highlights the need for a high index of suspicion for TPP in a patient with cardiopulmonary compromise and abdominal distension after upper GI endoscopic procedures even in the absence of identifiable perforations. Close coordination among gastroenterologists, anesthesiologists, and surgeons is key in prevention, recognition, and management of this rare but catastrophic complication.

Tension pneumoperitoneum (TPP), also known as hyperacute abdominal compartment syndrome or abdominal tamponade, is a rare condition most commonly associated with gastrointestinal (GI) perforation during endoscopy and iatrogenic insufflation of gas into the peritoneal cavity.¹ Other reported causes of TPP include gastric rupture after cardiopulmonary resuscitation, barotrauma during scuba diving, positive pressure ventilation through pleural-peritoneal channels, and spontaneous TPP of uncertain mechanism.^1-4

Case Presentation

A 76-year-old male with a history of ischemic cardiomyopathy, hypertension, and diabetes mellitus presented to the VA Puget Sound Health Care System in Seattle, Washington emergency department with painless jaundice, hematemesis, melena, and acute renal failure. On esophagogastroduodenoscopy (EGD), he was found to have an ulcer on the posterior wall of the duodenal bulb. The ulcer was coagulated and injected with epinephrine. The patient’s subsequent hospital course was complicated by worsening liver function, the need for renal replacement therapy, and recurrence of upper GI bleeding that required a transcatheter embolization of 2 separate superior pancreaticoduodenal arteries (SPDA) and the inferior pancreaticoduodenal artery (IPDA).

Once clinically stable, an endoscopic retrograde cholangiopancreatography (ERCP) was performed to evaluate for cholangiocarcinoma. A stricture was discovered in the common hepatic duct, brushings were taken, and a 15 cm, 7 Fr stent was placed in the common hepatic duct. The procedure was performed with an Olympus TJF Type Q180V duodenovideoscope (Tokyo, Japan) with an external diameter of 13.7 mm. The patient became hypotensive during the procedure and was treated with phenylephrine and ephedrine boluses. There was no endoscopic evidence of bleeding or bowel trauma.

After completion of the procedure, in the recovery area the patient became severely hypotensive and unresponsive. The physical examination was noteworthy for gross abdominal distention. Arterial blood gas analysis revealed severe metabolic and respiratory acidosis. Chest radiography demonstrated massive pneumoperitoneum, low lung volumes, and diaphragmatic compression (Figure).

Discussion

In relation to upper GI endoscopic procedures, TPP has been reported after diagnostic EGD, endoscopic sphincterotomy, and submucosal tumor dissection.^5-7 During these interventions, clinically apparent or overt iatrogenic perforations can occur either in the stomach or duodenum. These perforations may function as one-way valves that cause massive air accumulation and marked elevation of the diaphragm, which severely decreases lung volumes, pulmonary compliance, and limits gas exchange. Hemodynamically, compression of the inferior vena cava restricts venous return to the heart, resulting in decreased cardiac output.⁸

Patients with TPP present in acute distress with dyspnea, abdominal pain, and shock. On physical examination the abdomen is markedly distended, tympanic, and rigid. Rectal prolapse and subcutaneous emphysema also may be present.⁹ Roentographic features of TPP include findings of intraperitoneal air with elevation of the diaphragm, medial displacement of the liver (saddlebag sign), and juxtaposition of air in visceral interfaces, making intra-abdominal structures (spleen and gallbladder) appear more discrete.¹⁰ Abdominal computer tomography may show massive pneumoperitoneum with bowel loop compression and centralization of abdominal organs.⁴

Treatment strategies include emergent decompression either with percutaneous catheter insertion or abdominal drain placement followed by a definitive surgical repair. As with management of tension pneumothorax, treatment should not be delayed while awaiting confirmatory radiologic studies.⁹ When percutaneous needle decompression is undertaken, it is preferable to use a large bore (14-gauge venous catheter) and to advance a catheter over a needle to minimize the risk of visceral injury with egress of air and return of abdominal organs to their normal anatomical positions. The needle should be inserted directly above or below the umbilicus or in the left or right lower quadrants to avoid solid organ (ie, liver or spleen) injury.

Etiologic possibilities for the duodenal perforation in this case include mechanical trauma from the endoscope and duodenal tissue infarction after embolization of a bleeding duodenal ulcer. The duodenum and pancreatic head have a dual blood supply from the SPDA, a branch of the gastroduodenal artery, and the IPDA, a branch of the superior mesenteric artery.¹¹ After failed endoscopic management of persistent duodenal hemorrhage, the patient underwent synchronous embolization of 2 separate SPDAs and the IPDA. This might have put the first 2 segments of the duodenum at risk for ischemic damage and caused it to perforate at some point during the patient’s hospitalization (as evidenced by the bilious ascitis) or rendered them vulnerable to perforation from intraluminal insufflation during endoscopy.¹²

During the laparotomy, a pinhole-sized perforation was noted in the anterior wall of the second part of the duodenum, distinct form the duodenal ulcer present on the posterior wall. This perforation likely provided a pathway for the intraluminal gas to escape into the peritoneal cavity, culminating in abdominal tamponade, cardiopulmonary deterioration, and arrest. Needle decompression of the abdominal cavity provided an effective, though temporizing relief of this pressure, enabling return of spontaneous circulation.

This case highlights the need for a high index of suspicion for TPP in a patient with cardiopulmonary compromise and abdominal distension after upper GI endoscopic procedures even in the absence of identifiable perforations. Close coordination among gastroenterologists, anesthesiologists, and surgeons is key in prevention, recognition, and management of this rare but catastrophic complication.

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

For more details on letermovir, see the full prescribing information.

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

For more details on letermovir, see the full prescribing information.

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

CMV infection

The US Food and Drug Administration (FDA) has approved the oral and intravenous formulations of letermovir (PREVYMIS™).

Letermovir is a member of a new class of non-nucleoside CMV inhibitors known as 3,4 dihydro-quinazolines.

The FDA approved letermovir as prophylaxis for cytomegalovirus (CMV) infection and disease in adult recipients of allogeneic hematopoietic stem cell transplants (HSCTs) who are CMV-seropositive.

“PREVYMIS is the first new medicine for CMV infection approved in the US in 15 years,” said Roy Baynes, senior vice president, head of clinical development, and chief medical officer of Merck Research Laboratories, the company marketing letermovir.

Letermovir is expected to be available in December. The list price (wholesaler acquisition cost) per day is $195.00 for letermovir tablets and $270.00 for letermovir injections. (Wholesaler acquisition costs do not include discounts that may be paid on the product.)

The recommended dosage of letermovir is 480 mg once daily, initiated as early as day 0 and up to day 28 post-transplant (before or after engraftment) and continued through day 100. If letermovir is co-administered with cyclosporine, the dosage of letermovir should be decreased to 240 mg once daily.

Letermovir is available as 240 mg and 480 mg tablets, which may be administered with or without food. Letermovir is also available as a 240 mg and 480 mg injection for intravenous infusion via a peripheral catheter or central venous line at a constant rate over 1 hour.

For more details on letermovir, see the full prescribing information.

Trial results

The FDA’s approval of letermovir was supported by results of a phase 3 trial of adult recipients of allogeneic HSCTs who were CMV-seropositive. Patients were randomized (2:1) to receive either letermovir (at a dose of 480 mg once-daily, adjusted to 240 mg when co-administered with cyclosporine) or placebo.

Study drug was initiated after HSCT (at any time from day 0 to 28 post-transplant) and continued through week 14 post-transplant. Patients were monitored through week 24 post-HSCT for the primary efficacy endpoint, with continued follow-up through week 48.

Among the 565 treated patients, 34% were engrafted at baseline, and 30% had one or more factors associated with additional risk for CMV reactivation. The most common primary reasons for transplant were acute myeloid leukemia (38%), myelodysplastic syndromes (16%), and lymphoma (12%).

Thirty eight percent of patients in the letermovir arm and 61% in the placebo arm failed prophylaxis.

Reasons for failure (in the letermovir and placebo arms, respectively) included:

• Clinically significant CMV infection—18% vs 42%
• Initiation of PET based on documented CMV viremia—16% vs 40%
• CMV end-organ disease—2% for both
• Study discontinuation before week 24—17% vs 16%
• Missing outcome in week 24 visit window—3% for both.

The stratum-adjusted treatment difference for letermovir vs placebo was -23.5 (95% CI, -32.5, -14.6, P<0.0001).

The Kaplan-Meier event rate for all-cause mortality in the letermovir and placebo arms, respectively, was 12% and 17% at week 24 and 24% and 28% at week 48.

Common adverse events (in the letermovir and placebo arms, respectively) were nausea (27% vs 23%), diarrhea (26% vs 24%), vomiting (19% vs 14%), peripheral edema (14% vs 9%), cough (14% vs 10%), headache (14% vs 9%), fatigue (13% vs 11%), and abdominal pain (12% vs 9%).

The cardiac adverse event rate (regardless of investigator-assessed causality) was 13% in the letermovir arm and 6% in the placebo arm. The most common cardiac adverse events (in the letermovir and placebo arms, respectively) were tachycardia (4% vs 2%) and atrial fibrillation (3% vs 1%).

Results from this trial were presented at the 2017 BMT Tandem Meetings.

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo from Business Wire

The US Food and Drug Administration (FDA) has expanded the approved use of brentuximab vedotin (BV, ADCETRIS).

BV is now approved for adults with primary cutaneous anaplastic large-cell lymphoma (pcALCL) and CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.

This is the fourth FDA-approved indication for BV. The drug has regular approval for 2 indications in classical Hodgkin lymphoma and accelerated approval for the treatment of systemic ALCL.

In November 2016, the FDA granted BV breakthrough therapy designation for the treatment of patients with pcALCL and CD30-expressing MF who require systemic therapy and have received one prior systemic therapy. The agency also granted the supplemental biologics license application priority review.

The approval for BV in pcALCL and CD30-expressing MF is based on data from the phase 3 ALCANZA trial and a pair of phase 2 investigator-sponsored trials.

Phase 3 trial

Results from ALCANZA were presented at the 9th Annual T-cell Lymphoma Forum in January and published in The Lancet in June.

There were 128 patients in the intent-to-treat and safety populations. Sixty-four patients (48 with MF and 16 with pcALCL) were randomized to receive BV at 1.8 mg/kg every 3 weeks for up to 48 weeks.

The other 64 patients (49 with MF and 15 with pcALCL) were randomized to receive standard of care (SOC)—methotrexate at 5 mg to 50 mg weekly or bexarotene at a target dose of 300 mg/m² daily for up to 48 weeks.

The study’s primary endpoint was the rate of objective response lasting at least 4 months (ORR4). The ORR4 rate was significantly higher with BV than with SOC—56.3% and 12.5%, respectively (P<0.0001).

For patients with MF, the ORR4 was 50% with BV and 10% with SOC. For patients with pcALCL, the ORR4 was 75% with BV and 20% with SOC.

Overall, the complete response (CR) rates were 15.6% in the BV arm and 1.6% in the SOC arm (P=0.0046).

For patients with MF, the CR rate was 10% with BV and 0% with SOC. For patients with pcALCL, the CR rate was 31% with BV and 7% with SOC.

Progression-free survival (PFS) was significantly longer in the BV arm than the SOC arm. The median PFS was 16.7 months and 3.5 months, respectively. The hazard ratio was 0.270 (P<0.0001).

For patients with MF, the median PFS was 15.9 months with BV and 3.5 months with SOC. For patients with pcALCL, the median PFS was 27.5 months with BV and 5.3 months with SOC.

The most common adverse events (AEs) of any grade (occurring in 15% or more of patients in the BV and SOC arms, respectively) were peripheral neuropathy (67% and 6%), nausea (36% and 13%), diarrhea (29% and 6%), fatigue (29% and 27%), vomiting (17% and 5%), alopecia (15% and 3%), pruritus (17% and 13%), pyrexia (17% and 18%), decreased appetite (15% and 5%), and hypertriglyceridemia (2% and 18%).

Phase 2 trials

Data from the investigator-sponsored trials were published in the Journal of Clinical Oncology in 2015.

The first study was published in July of that year. The trial enrolled 32 patients with MF or Sézary syndrome. Thirty patients were evaluable for efficacy, and more than half had received 3 or more prior systemic therapies.

Patients received BV (1.8 mg/kg) every 3 weeks for a maximum of 16 doses. The primary endpoint was objective clinical response rate.

Seventy percent of patients (21/30) achieved an objective response across all stages of disease. One patient had a CR, 20 had a partial response, 4 had stable disease, 5 had progressive disease, and 2 were not evaluable for response.

The most common related AEs of any grade were peripheral neuropathy (66%), fatigue (47%), nausea (28%), hair loss (22%), and neutropenia (19%). Grade 3/4 related AEs included neutropenia (n=4), rash (n=3), and peripheral neuropathy (n=1).

The second phase 2 trial was published in August 2015. This trial enrolled CD30-positive patients with lymphomatoid papulosis (LyP), pcALCL, and MF.

Fifty-four patients were enrolled, and 48 were evaluable at the time of analysis. Patients had received an infusion of BV (1.8 mg/kg) every 21 days.

Seventy-three percent of patients (35/48) achieved an objective response, including 100% (20/20) with LyP and/or pcALCL and 54% (15/28) with MF. The CR rate was 35% (n=17).

The most common AEs were peripheral neuropathy (67%), fatigue (35%), skin rash (24%), diarrhea (15%), muscle pain (17%), localized skin infection (15%), neutropenia (15%), and hair loss (11%).

Grade 3/4 AEs included neutropenia (n=3), nausea (n=2), unstable angina or myocardial infarction (n=2), infection (n=2), joint pain (n=2), fatigue (n=1), deep vein thrombosis (n=1), pulmonary embolism (n=1), aminotransferase elevation (n=1), and dehydration (n=1).

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has approved use of an intravenous (IV) formulation of aprepitant (CINVANTI™) to prevent chemotherapy-induced nausea and vomiting (CINV).

CINVANTI is intended to be used in combination with other antiemetic agents to prevent acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).

CINVANTI is to be used in combination with a 5-HT3 receptor antagonist and dexamethasone.

The full prescribing information is available at www.cinvanti.com.

The US commercial launch of CINVANTI is planned for January 2018.

CINVANTI is the first IV formulation to directly deliver aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist.

Aprepitant is also the active ingredient in EMEND^® capsules, which were approved by the FDA in 2003. EMEND IV^®, which was approved in 2008, contains aprepitant’s prodrug, fosaprepitant.

Heron Therapeutics, Inc., developed CINVANTI in an attempt to provide an IV formulation of aprepitant that has the same efficacy as IV fosaprepitant but does not pose the risk of adverse events (AEs) related to polysorbate 80.

“Aprepitant has long been the standard in the NK1 class, and it remains the only single-agent NK1 with proven efficacy in preventing CINV in both the acute and delayed phases in HEC and MEC,” said Rudolph M. Navari, MD, PhD, of the University of Alabama Birmingham School of Medicine.

“Because CINVANTI is a novel, polysorbate 80-free, IV formulation of aprepitant, it enables physicians to provide patients with standard-of-care efficacy without the potential risk of polysorbate 80-related adverse events, such as infusion-site reactions.”

The FDA approved CINVANTI based on data demonstrating the bioequivalence of CINVANTI to EMEND IV.

A phase 1, randomized, 2-way cross-over study comparing the drugs enrolled 100 healthy subjects. The subjects received CINVANTI at 130 mg or EMEND IV at 150 mg, given over 30 minutes on day 1 of periods 1 and 2.

The researchers said 90% confidence intervals for CINVANTI AUC_0-t (area under the time-concentration curve from time 0 to the last measurable concentration), AUC_0-inf (area under the time-concentration curve from time 0 extrapolated to infinity), and C12h (plasma concentration at 12 hours) “were well within bioequivalence bounds,” which was 80% to 125%.

The team also found the incidence of treatment-emergent AEs was lower with CINVANTI than EMEND IV—21% and 28%, respectively. The same was true for related treatment-emergent AEs—15% and 28%, respectively.

These data were presented at the Hematology/Oncology Pharmacy Association Annual Conference in March/April and the Multinational Association of Supportive Care in Cancer (MASCC)/International Society of Oral Oncology (ISOO) Annual Meeting in June.

A 65-year-old woman is admitted to your inpatient service from the family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a five-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a history of hypertension and diabetes, both of which have been controlled by oral medications. Antibiotic therapy is initiated—but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for successful treatment of CAP.

In 2007, the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines for the treatment of CAP.³ These guidelines recommend a minimum five-day course of antibiotics if the patient is clinically stable (defined as afebrile for 48 h; heart rate ≤ 100 beats/min; respiratory rate ≤ 24 breaths/min^-1; systolic blood pressure ≥ 90 mm Hg; oxygen saturation ≥ 90%; normal mental status; and able to tolerate oral intake). Longer antibiotic treatment durations are recommended on an individualized basis (eg, if the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source).

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ Yet, we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- and long-course antibiotic therapy in CAP (≤ 7 d vs > 7 d, respectively).^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotics for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

However, there are limitations to broad implementation. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 d vs 5 d) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a five-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 d) to physician-discretion antibiotic treatment duration among 312 patients (ages 18 and older) admitted for CAP to one of four teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

After receiving a minimum of five days of antibiotics, patients were randomly assigned to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹

Primary outcomes were clinical success rate at days 10 and 30 from admission (defined as resolution of signs and symptoms of CAP without further antibiotics) and improvement of CAP-related symptoms (as determined by an 18-item questionnaire scored 0-90, with higher scores indicative of greater severity). Secondary outcomes included duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹

Of the 312 participants, 162 were randomized to the intervention group and 150 to the control group. Mean age of patients in the intervention and control groups was 66.2 and 64.7, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; < 10% received a ß-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups at day 10 (49% vs 56%, respectively) and day 30 (89% vs 92%). Median antibiotic treatment duration was shorter in the intervention group than in the control group (5 d vs 10 d); the intervention group also had a lower rate of 30-day hospital readmissions (1.4% vs 6.6%). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a five-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk for adverse events.

CAVEATS

Generalizability is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (eg, fever or low oxygen saturation on room air) after five days of antibiotics, treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than five days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement

In this study, it took an average of 12 days in both groups for patients to achieve clinical improvement, and upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017; 66[10]:629-631).

A 65-year-old woman is admitted to your inpatient service from the family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a five-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a history of hypertension and diabetes, both of which have been controlled by oral medications. Antibiotic therapy is initiated—but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for successful treatment of CAP.

In 2007, the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines for the treatment of CAP.³ These guidelines recommend a minimum five-day course of antibiotics if the patient is clinically stable (defined as afebrile for 48 h; heart rate ≤ 100 beats/min; respiratory rate ≤ 24 breaths/min^-1; systolic blood pressure ≥ 90 mm Hg; oxygen saturation ≥ 90%; normal mental status; and able to tolerate oral intake). Longer antibiotic treatment durations are recommended on an individualized basis (eg, if the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source).

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ Yet, we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- and long-course antibiotic therapy in CAP (≤ 7 d vs > 7 d, respectively).^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotics for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

However, there are limitations to broad implementation. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 d vs 5 d) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a five-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 d) to physician-discretion antibiotic treatment duration among 312 patients (ages 18 and older) admitted for CAP to one of four teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

After receiving a minimum of five days of antibiotics, patients were randomly assigned to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹

Primary outcomes were clinical success rate at days 10 and 30 from admission (defined as resolution of signs and symptoms of CAP without further antibiotics) and improvement of CAP-related symptoms (as determined by an 18-item questionnaire scored 0-90, with higher scores indicative of greater severity). Secondary outcomes included duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹

Of the 312 participants, 162 were randomized to the intervention group and 150 to the control group. Mean age of patients in the intervention and control groups was 66.2 and 64.7, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; < 10% received a ß-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups at day 10 (49% vs 56%, respectively) and day 30 (89% vs 92%). Median antibiotic treatment duration was shorter in the intervention group than in the control group (5 d vs 10 d); the intervention group also had a lower rate of 30-day hospital readmissions (1.4% vs 6.6%). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a five-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk for adverse events.

CAVEATS

Generalizability is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (eg, fever or low oxygen saturation on room air) after five days of antibiotics, treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than five days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement

In this study, it took an average of 12 days in both groups for patients to achieve clinical improvement, and upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017; 66[10]:629-631).

A 65-year-old woman is admitted to your inpatient service from the family health center. She is diagnosed with community-acquired pneumonia (CAP) based on a five-day history of cough and fever and a positive chest x-ray. She now requires oxygen at rest. She has a history of hypertension and diabetes, both of which have been controlled by oral medications. Antibiotic therapy is initiated—but what treatment duration is ideal?

The World Health Organization estimates that pneumonia is the third most common cause of mortality worldwide, causing 3.2 million deaths per year.² Appropriate prescribing of antibiotics is critical for successful treatment of CAP.

In 2007, the Infectious Diseases Society of America (IDSA) and the American Thoracic Society (ATS) created consensus guidelines for the treatment of CAP.³ These guidelines recommend a minimum five-day course of antibiotics if the patient is clinically stable (defined as afebrile for 48 h; heart rate ≤ 100 beats/min; respiratory rate ≤ 24 breaths/min^-1; systolic blood pressure ≥ 90 mm Hg; oxygen saturation ≥ 90%; normal mental status; and able to tolerate oral intake). Longer antibiotic treatment durations are recommended on an individualized basis (eg, if the isolated pathogen is not susceptible to the initial antibiotic or if the infection was caused by an extrapulmonary source).

However, these recommendations are not routinely followed. Practitioners often make it their custom to prescribe longer courses of antibiotics.⁴ Yet, we know that there are several reasons to consider shorter courses of antibiotics, including lower health care costs, fewer adverse effects, and lower rates of bacterial resistance.^5-7

Two meta-analyses were performed to compare the safety and efficacy of short- and long-course antibiotic therapy in CAP (≤ 7 d vs > 7 d, respectively).^8,9 Both meta-analyses found no difference in efficacy or safety between shorter and longer courses of antibiotics for CAP. Secondary outcomes noted a trend toward decreased antibiotic-associated adverse events with shorter courses of therapy.^8,9

However, there are limitations to broad implementation. Studies included in these analyses utilized a variety of antibiotic treatment regimens and longer courses (7 d vs 5 d) that are not recommended by the IDSA/ATS guidelines. Additionally, studies included both inpatient and outpatient treatment groups, so findings may not apply to an exclusively inpatient CAP population.^8,9

This study sought to validate the IDSA/ATS guidelines recommending a five-day course of antibiotics for hospitalized patients with CAP.¹

STUDY SUMMARY

No differences in clinical outcomes

This multicenter, double-blind, noninferiority randomized trial compared short-term antibiotic treatment duration (5 d) to physician-discretion antibiotic treatment duration among 312 patients (ages 18 and older) admitted for CAP to one of four teaching hospitals in Spain.¹ Pneumonia was diagnosed on chest radiograph with at least one symptom: cough, fever, dyspnea, or chest pain. Patients were excluded if, among other things, they had an immunocompromising condition, lived in a nursing home, had a recent hospital stay, used antibiotics within the previous 30 days, or had an uncommon pathogen, such as Pseudomonas aeruginosa or Staphylococcus aureus.¹

After receiving a minimum of five days of antibiotics, patients were randomly assigned to an intervention group (where, if clinically stable, no further antibiotics were given) or a control group (where physicians determined antibiotic duration).¹

Primary outcomes were clinical success rate at days 10 and 30 from admission (defined as resolution of signs and symptoms of CAP without further antibiotics) and improvement of CAP-related symptoms (as determined by an 18-item questionnaire scored 0-90, with higher scores indicative of greater severity). Secondary outcomes included duration of antibiotic use, time to clinical improvement, mortality, hospital readmission, hospital length of stay, and CAP recurrence.¹

Of the 312 participants, 162 were randomized to the intervention group and 150 to the control group. Mean age of patients in the intervention and control groups was 66.2 and 64.7, respectively. Other baseline demographics were similar between the groups. Nearly 80% of patients received quinolone treatment; < 10% received a ß-lactam plus a macrolide.¹

Clinical success rates were similar for the control and intervention groups at day 10 (49% vs 56%, respectively) and day 30 (89% vs 92%). Median antibiotic treatment duration was shorter in the intervention group than in the control group (5 d vs 10 d); the intervention group also had a lower rate of 30-day hospital readmissions (1.4% vs 6.6%). There were no differences for other secondary outcomes.¹

WHAT’S NEW

Clinical support for 2007 guidelines

This is the first study to clinically support the IDSA/ATS guidelines, which state that a five-day course of antibiotic therapy for hospitalized adults with CAP is effective and without increased risk for adverse events.

CAVEATS

Generalizability is unclear

This study focused on antibiotic duration for the treatment of CAP in hospitalized patients and mainly used quinolone antibiotics. It remains unclear if duration of therapy is as effective in the outpatient setting or when using alternative antibiotic regimens.

If patients continued to have symptoms (eg, fever or low oxygen saturation on room air) after five days of antibiotics, treatment was continued in the study. Thus, patients in real life who continue to have symptoms may need individualized therapy and may require more than five days of antibiotics.

CHALLENGES TO IMPLEMENTATION

Antibiotics end before clinical improvement

In this study, it took an average of 12 days in both groups for patients to achieve clinical improvement, and upwards of 15 to 18 days for patients to return to normal activity. Patients and providers may be dissatisfied if the treatment course ends days before clinical improvement of symptoms. This may cause prescribers to lengthen the duration of antibiotic therapy inappropriately.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017; 66[10]:629-631).

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

[email protected]

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

[email protected]

The FDA has granted regular approval to brentuximab vedotin for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Approval was based on a 56% objective response rate for brentuximab vedotin versus 12% for physician’s choice in a phase 3 trial (ALCANZA) of 131 patients with mycosis fungoides or pcALCL. All patients had received one prior systemic therapy and were randomized (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene, the Food and Drug Administration said in a press statement.

[email protected]

PARIS – A report that adjunctive minocycline was found safe and effective for treatment of schizophrenia must be considered one of the year’s highlights in the field of psychosis, Pascal Steullet, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

The report came in the form of a meta-analysis conducted by investigators in China and Australia. This was the largest meta-analysis looking at the topic to date, and the only one to include a search of the Chinese language database, which provided three of the eight randomized, placebo-controlled clinical trials that were examined. Seven of the eight randomized trials were double-blind and deemed high quality by widely used criteria, including the Jadad scale and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, noted Dr. Steullet, a neuroscientist at the University of Lausanne (Switzerland).

[email protected]

PARIS – A report that adjunctive minocycline was found safe and effective for treatment of schizophrenia must be considered one of the year’s highlights in the field of psychosis, Pascal Steullet, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

The report came in the form of a meta-analysis conducted by investigators in China and Australia. This was the largest meta-analysis looking at the topic to date, and the only one to include a search of the Chinese language database, which provided three of the eight randomized, placebo-controlled clinical trials that were examined. Seven of the eight randomized trials were double-blind and deemed high quality by widely used criteria, including the Jadad scale and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, noted Dr. Steullet, a neuroscientist at the University of Lausanne (Switzerland).

[email protected]

PARIS – A report that adjunctive minocycline was found safe and effective for treatment of schizophrenia must be considered one of the year’s highlights in the field of psychosis, Pascal Steullet, PhD, said at the annual congress of the European College of Neuropsychopharmacology.

The report came in the form of a meta-analysis conducted by investigators in China and Australia. This was the largest meta-analysis looking at the topic to date, and the only one to include a search of the Chinese language database, which provided three of the eight randomized, placebo-controlled clinical trials that were examined. Seven of the eight randomized trials were double-blind and deemed high quality by widely used criteria, including the Jadad scale and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, noted Dr. Steullet, a neuroscientist at the University of Lausanne (Switzerland).

[email protected]

The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:

• TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
• REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
• PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
• ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
• HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.

[email protected]

On Twitter @cardionews

The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:

• TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
• REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
• PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
• ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
• HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.

[email protected]

On Twitter @cardionews

The final Late-Breaking Science session delves into innovative therapies and novel applications, including two phase 1-2 stem cell trials, an early trial in toxin treatments to prevent atrial fibrillation, a phase 1 test of an interatrial shunt device for heart failure with preserved ejection fraction, and more:

• TNT-POAF: Nathan Waldron, MD, of Duke University, Durham, N.C., will present results of a trial aiming to prevent postoperative atrial fibrillation with the use of temporary toxin treatment.
• REDUCE LAP–HF 1: In what the investigators call the first randomized controlled trial of a device-based therapy to reduce left atrial pressure in HFpEF, an inter-atrial shunt device designed to provide continuous and dynamic decompression of the left atrium. Sanjiv J Shah, MD, of Northwestern University will present the study, which holds the hypothesis that the device may reduce symptoms and slow the progression of heart failure.
• PROPEL: This study tested the hypothesis that granulocyte-macrophage colony-stimulating factor (GM-CSF) combined with supervised treadmill exercise in patients with peripheral artery disease would significantly improve functional performance more than GM-CSF alone or supervised treadmill exercise alone. Mary McDermott, MD, of Northwestern University, Chicago, will present the primary endpoint of change in 6-minute walk performance at 12-weeks’ follow-up, as well as several secondary outcomes.
• ALLSTAR: Timothy Henry, MD, of the Cedars-Sinai Heart Institute, Los Angeles, will present the phase 1-2 ALLSTAR (Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration) study, which compared allogeneic cardiosphere-derived cells (CAP-1002) to placebo in order to find whether it is safe and effective in decreasing infarct size in patients with an MI.
• HOPE-Duchenne: This phase 1-2 study randomized men with cardiomyopathy secondary to Duchenne muscular dystrophy to receive CAP-1002 cells or usual care; its primary outcome is safety. Ronald Victor, MD, will present the results.

[email protected]

On Twitter @cardionews

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny

The Food and Drug Administration has given the biopharmaceutical company Cellectis permission to resume phase 1 trials of UCART123, a gene-edited T-cell investigational drug that targets CD123, as a potential treatment for acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN), according to a press release from the company.

UCART123 is the first allogeneic, “off-the-shelf” gene-edited chimeric antigen receptor (CAR) T-cell product candidate that the FDA has approved for clinical trials. The agency had placed a clinical hold on phase 1 trials of the gene-edited CAR T-cell drug on Sept. 4, following a patient death in the BPDCN clinical study. In order to proceed with the trials, Cellectis agreed to several changes in the study protocols.

The changes include decreasing the dose of the UCART123 therapy to 6.25x10⁴ cells/kg and lowering the dose of the lympho-depleting regimen of cyclophosphamide to 750 mg/m² per day over 3 days with a maximum daily dose of 1.33 g. Additionally, there can be no uncontrolled infection after receipt of the lympho-depleting preconditioning regimen. Patients must be afebrile at the start of treatment, off all but a replacement dose of corticosteroids, and have no organ dysfunction. Plus, the next three patients treated in each study must be under age 65.

There’s also a condition that patient enrollments be staggered by at least 28 days.

The drug sponsor is working with investigators and each clinical site to obtain the Institutional Review Board’s approval of the revised protocols.

The hold followed the death of a 78-year-old man with relapsed/refractory BPDCN with 30% blasts in his bone marrow and cutaneous lesions. The first dose of UCART123 at 6.25x10⁵ cells/kg was administered without complication, but at day 5 the patient began experiencing side effects, including cytokine release syndrome and a lung infection. At day 8, the cytokine release syndrome had worsened and the patient had also developed capillary leak syndrome. He died on day 9 of the study.

In the AML phase 1 study, a 58-year-old woman with AML and 84% blasts in her bone marrow received the same dose of UCART123. She also developed cytokine release syndrome and capillary leak syndrome but both resolved with treatment.

Both patients also received the same preconditioning treatment: 30 mg/m² per day fludarabine for 4 days and 1g/m² per day cyclophosphamide for 3 days.

[email protected]

On Twitter @maryellenny