Headline is a bit misleading in my opinion.
MedPage Today
But no safety concerns either; research likely to continue
by Ed Susman
9-4-16
ROME -- In one of the largest heart stem cell studies undertaken, injections of stem cells directly into the cardiac muscle did not improve outcomes versus sham procedures, researchers reported here.
There were 11 deaths in the active group – 9.2% of the 120 patients treated; and 12 deaths in the sham group or 7.9% of 151 patients (P=0.27).
"This was a neutral trial" in terms of efficacy, said Jozef Bartunek, MD, from the Cardiovascular Center, Aalst, Belgium, at the European Society of Cardiology annual congress. "We showed that cardiopoietic cell treatment was safe."
There was no significant difference in the primary outcome measure: a composite of all-cause mortality, worsening heart failure by the Minnesota Living with Heart Failure Questionnaire total score, the 6-minute walk distance, and left ventricular end-systolic volume and ejection fraction, Bartunek said.
He said there was a lower incidence of sudden death and aborted sudden death in the active group, with an 84% reduction in these events (P=0.04). There were no sudden deaths in the stem cell groups while four sudden deaths occurred in the sham group. There was one aborted sudden death in the stem cell group and five in the sham patients.
However, he said there were glimmers of positivity when looking at secondary and exploratory subgroups of patients. He especially noted that patients with severe heart failure – a baseline left ventricular end-systolic volume of 200-370 mL -- did well with the stem cell injections, reducing the risk of experiencing the primary endpoint by 39% (P=0.015). There were 66 patients with severe heart failure who received stem cells, and 96 patients assigned to the sham injections.
In this group, "outcomes for all components of the composite endpoint were directionally consistent. The effect was also related to clinically meaningful improved quality of life, greater 6-minute walk distance and reduced left ventricular end-systolic volume for cell treatment versus sham," he said.
Bartunek also reported that patients reported better quality of life – 68% of the active treatment patients showing better than a 10-point improvement versus 49% of the control group (P=0.04). More than a 40-meter improvement in the 6-minute walk test was achieved by 43% of the active treatment patients compared with 25% of the control population in the subgroup.
While the secondary and exploratory endpoints indicated some promise, Frank Ruschitzka, MD, of the University Heart Center Zurich, cautioned, "We should not get carried away with exploratory analysis in a trial that was neutral on the primary endpoint as a general rule in clinical trials." Ruschitzka was not involved in the study.
Bartunek said in a press conference, "Cardiopoietic cells provide a unique approach for advanced ischemic heart failure patients. Ischemic heart failure with extensive cardiac enlargement yields poor outcome, a still unmet clinical need. Cell therapy is a paradigm-shifting intervention that targets organ restoration. Cardiopoietic cells derived by cardiogenic specification of patient's own mesenchymal stem cells showed clinical promise as next generation therapy."
In the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial, conducted in 39 centers in Europe and Israel, patients diagnosed with ischemic heart failure on standard-of-care were assigned to receive either cardiopoietic cell therapy or a sham procedure. The cell were placed through endomyocardial delivery using a catheter-based system. Patients and evaluators were blinded to treatment assignments.
Bartunek also said the researchers found an intriguing relationship between outcomes and the number of injections that were performed. In patients receiving fewer than 20 injections, there was a greater probability of a better outcome overall (P<0.001).
When pressed by session co-moderator Mariell Jessup, MD, of the University of Pennsylvania Hospital in Philadelphia, to explain this "counterintuitive" outcome, Bartunek said the researchers were not really sure what the finding represented other than a possible better response achieved earlier.
Bartunek said that, overall, there were key lessons that were learned from the CHART-1 trial: it identified a clinically relevant patient population with elevated baseline end-diastolic volume that benefited from cardiopoietic cell treatment.
Optimized treatment intensity together with disease severity-targeted patient selection should be considered for future trials and/or potential cell therapy application in heart failure, he said.
The trial was funded by Celyad of Mont St. Guibert, Belgium.
Ruschitzka disclosed no relevant relationships with industry.
Bartunek disclosed relevant relationships with Celyad.
Jessup disclosed no relevant relationships with industry.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine
MedPage Today
But no safety concerns either; research likely to continue
by Ed Susman
9-4-16
ROME -- In one of the largest heart stem cell studies undertaken, injections of stem cells directly into the cardiac muscle did not improve outcomes versus sham procedures, researchers reported here.
There were 11 deaths in the active group – 9.2% of the 120 patients treated; and 12 deaths in the sham group or 7.9% of 151 patients (P=0.27).
"This was a neutral trial" in terms of efficacy, said Jozef Bartunek, MD, from the Cardiovascular Center, Aalst, Belgium, at the European Society of Cardiology annual congress. "We showed that cardiopoietic cell treatment was safe."
There was no significant difference in the primary outcome measure: a composite of all-cause mortality, worsening heart failure by the Minnesota Living with Heart Failure Questionnaire total score, the 6-minute walk distance, and left ventricular end-systolic volume and ejection fraction, Bartunek said.
He said there was a lower incidence of sudden death and aborted sudden death in the active group, with an 84% reduction in these events (P=0.04). There were no sudden deaths in the stem cell groups while four sudden deaths occurred in the sham group. There was one aborted sudden death in the stem cell group and five in the sham patients.
However, he said there were glimmers of positivity when looking at secondary and exploratory subgroups of patients. He especially noted that patients with severe heart failure – a baseline left ventricular end-systolic volume of 200-370 mL -- did well with the stem cell injections, reducing the risk of experiencing the primary endpoint by 39% (P=0.015). There were 66 patients with severe heart failure who received stem cells, and 96 patients assigned to the sham injections.
In this group, "outcomes for all components of the composite endpoint were directionally consistent. The effect was also related to clinically meaningful improved quality of life, greater 6-minute walk distance and reduced left ventricular end-systolic volume for cell treatment versus sham," he said.
Bartunek also reported that patients reported better quality of life – 68% of the active treatment patients showing better than a 10-point improvement versus 49% of the control group (P=0.04). More than a 40-meter improvement in the 6-minute walk test was achieved by 43% of the active treatment patients compared with 25% of the control population in the subgroup.
While the secondary and exploratory endpoints indicated some promise, Frank Ruschitzka, MD, of the University Heart Center Zurich, cautioned, "We should not get carried away with exploratory analysis in a trial that was neutral on the primary endpoint as a general rule in clinical trials." Ruschitzka was not involved in the study.
Bartunek said in a press conference, "Cardiopoietic cells provide a unique approach for advanced ischemic heart failure patients. Ischemic heart failure with extensive cardiac enlargement yields poor outcome, a still unmet clinical need. Cell therapy is a paradigm-shifting intervention that targets organ restoration. Cardiopoietic cells derived by cardiogenic specification of patient's own mesenchymal stem cells showed clinical promise as next generation therapy."
In the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial, conducted in 39 centers in Europe and Israel, patients diagnosed with ischemic heart failure on standard-of-care were assigned to receive either cardiopoietic cell therapy or a sham procedure. The cell were placed through endomyocardial delivery using a catheter-based system. Patients and evaluators were blinded to treatment assignments.
Bartunek also said the researchers found an intriguing relationship between outcomes and the number of injections that were performed. In patients receiving fewer than 20 injections, there was a greater probability of a better outcome overall (P<0.001).
When pressed by session co-moderator Mariell Jessup, MD, of the University of Pennsylvania Hospital in Philadelphia, to explain this "counterintuitive" outcome, Bartunek said the researchers were not really sure what the finding represented other than a possible better response achieved earlier.
Bartunek said that, overall, there were key lessons that were learned from the CHART-1 trial: it identified a clinically relevant patient population with elevated baseline end-diastolic volume that benefited from cardiopoietic cell treatment.
Optimized treatment intensity together with disease severity-targeted patient selection should be considered for future trials and/or potential cell therapy application in heart failure, he said.
The trial was funded by Celyad of Mont St. Guibert, Belgium.
Ruschitzka disclosed no relevant relationships with industry.
Bartunek disclosed relevant relationships with Celyad.
Jessup disclosed no relevant relationships with industry.
Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine