The study included 97 patients at 24 medical centers in Europe. To be eligible for the study, patients had survived a heart attack and needed coronary artery bypass graft (CABG) surgery....
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...the researchers said they were encouraged by their findings regarding safety because the possibility that treatment would lead to increased arrhythmia had been a major concern...
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Late-Breaking Clinical Trial News Release 9
Implanting muscle cells to treat heart failure seems safe, promising
American Heart Association Scientific Sessions Late-Breaking News:
CHICAGO, Nov. 15, 2006 — Heart failure patients whose muscle cells were injected into their heart had a significant 12 percent to 13 percent reduction in left ventricular volume, researchers reported today at the American Heart Association’s Scientific Sessions 2006.
The results of the phase II, first randomized, placebo-controlled trial Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) were presented at a late-breaking clinical trials session.
“We have partly reversed remodeling (heart enlargement) in the high-dose treatment group,” said Philippe Menasché, M.D., Ph.D., lead author of the study and professor of thoracic and cardiovascular surgery and staff surgeon at L'Hôpital Européen Georges Pompidou in Paris, France. “This was a good surprise when the data were unblinded.”
The study included 97 patients at 24 medical centers in Europe. To be eligible for the study, patients had survived a heart attack and needed coronary artery bypass graft (CABG) surgery. During CABG surgery, veins from the leg or the mammary artery of the chest are harvested and grafted onto the arteries of the heart to bypass blockages. Patients in the study also had heart failure with a low left ventricular ejection fraction (LVEF), a measure of the heart’s pumping ability.
The 97 patients were randomized into three groups. The high-dose group (30 patients) received direct injections of myoblasts in and around the infarct area totaling about 800 million myoblasts via 30 injections. Myoblasts are precursor cells normally dormant in the muscle but after injury are mobilized, proliferate and fuse with one another to regenerate muscle fibers.
The low-dose group (33 Patients) received direct injections of about 400 million myoblasts.
The third group, the placebo group (34 patients), received injections of the suspension medium without active cells. Because the cells were autologous, meaning they came from the patients themselves, there was no risk of rejection.
All patients received an implanted cardioverter defibrillator (ICD), a small device that uses an electrical jolt to stop an irregular heartbeat and allow a normal rhythm to resume. That was done because heart failure (HF) patients are at increased risk of irregular heartbeat. Furthermore, an earlier phase I study of muscle cell implants in 10 HF patients by Menasché and his colleagues found an apparent increase in risk of arrhythmia in the first three weeks following the procedure.
The researchers ended the study early, after an analysis by an independent data-monitoring board indicated the trial was unlikely to show that the treatment was superior to placebo on the primary endpoints: functional improvements in heart regional wall motion (the area where cells were implanted) or global function, he said. The study failed to find any significant differences in either of those endpoints as measured by echocardiography, a diagnostic test that uses sound waves to image the heart and its motion. About 75 percent of the projected number of patients had completed the trial.
However, the researchers said they were encouraged by their findings regarding safety because the possibility that treatment would lead to increased arrhythmia had been a major concern. There were no statistically significant differences between the treatment and placebo groups in terms of major adverse cardiac events and ventricular arrhythmias, Menasché said.
The primary endpoints were based on echocardiography, a common test of heart function. Although the results failed to show a significant increase in ejection fraction or regional wall motion, a significant decrease was documented (by 12 percent-13 percent from baseline preoperative values) of left ventricular volumes (dimensions) in patients receiving the high dose of cells whereas there were no significant changes in the placebo group. Because left ventricular volumes are predictors of outcomes, this finding might be clinically relevant. Furthermore, ejection fraction was also measured by nuclear angiography in a subgroup of 48 patients and was then found to be significantly increased in those that had received the high dose of myoblasts compared with the placebo group.
“We were surprised and were happy to show there was apparently no increased risk in the procedure, and we also were encouraged by what appeared to be happening with the heart volume,” Menasché said. “However, I am cautiously optimistic because the main findings represent a small number of patients and need to be confirmed by larger studies. We want to avoid any over-hype.”
The MAGIC study will continue to follow all 97 patients to the one-year mark; the hope is to report those results next year.
“Heart failure is a major public health problem,” Menasché said. “Our objective at this early stage was to establish proof of principle and safety. Our study ended early but nevertheless showed some positive and encouraging signals. Heart volume reduction has been shown experimentally in animals several times, but this trial was the first human study with a control group that confirmed the reduction in heart volume in humans following myoblast transplantation, but only time will tell.”
Much has changed in the field of myoblast implantation since the MAGIC study began, and Menasché’s group is considering several protocols for future studies.
Countries in the study included: Belgium, France, Germany, Italy and the United Kingdom.
Presentation made on behalf of the MAGIC investigators.
Sponsors: Public funding came from Assistance Publique – Hôpitaux de Paris, a public organization that runs the teaching hospitals in Paris. Private funding came from Genzyme, whose laboratories in Framingham, Mass., provided the expanded myoblast cells for three of the countries (Belgium, Italy and the United Kingdom) involved in the study, whereas, the Paris lab supplied France and Germany.
Disclosures: Dr. Menasché was a consultant for Genzyme.
Statements and conclusions of abstracts presented at American Heart Association scientific meetings are solely those of the authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
NR06-1127 (SS06/Menasché/MAGIC)