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Stem cell trial failed to meet primary endpoint, but data advance the field
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CHICAGO — A new study found that using a patient’s own bone marrow cells did not result in improvement in most measures of heart function.
Researchers for the FOCUS-Cardiovascular Cell Therapy Research Network (FOCUS-CCTRN) trial found no statistically significant differences at 6 months between patients with chronic ischemic heart disease along with HF and/or angina who received stem cells or placebo for the primary endpoints of change in left-ventricular end-systolic volume assessed by echocardiography (–0.9 mL/m2; P=.73), maximal oxygen consumption (1.0; P=.17) and reversible defect on single-photo emission tomography (–1.2; P=.84). There were also no differences in secondary outcomes, including LV end-diastolic volume, percent myocardial defect and clinical improvement, according to results presented at the American College of Cardiology 61st Scientific Sessions.
Patients who received stem cell therapy had a small but significant increase of 2.7% in LV ejection fraction. The magnitude of the study also revealed that the improvement in LVEF correlated with the number of CD34+ and CD133+ cells in bone marrow at the time of cell implantation.
FOCUS-CCTRN is the largest study to date to look at the effects of using a patient’s own stem/progenitor cells to repair damaged areas of the heart in patients with chronic ischemic heart disease and LV dysfunction.
“This is the kind of information we need to move forward with the clinical use of stem cell therapy,” Emerson C. Perin, MD, PhD, director of clinical research for CV medicine at Texas Heart Institute, said in a press release.
The early phase 2 study included 92 patients (82 men; mean age, 63 years) with chronic ischemic heart disease and LVEF ≤45% along with HF and/or angina who were no longer candidates for revascularization. Sixty-one patients were randomly assigned to receive transendocardial injection of bone marrow cells and 31 to injection with placebo. This study was sponsored by the National Heart, Lung and Blood Institute and was conducted from 2009 to 2011.
Bone marrow was aspirated from the patients and processed to obtain just the mononuclear fraction of the marrow. In patients randomly assigned to receive stem/progenitor cell therapy, researchers inserted a catheter into the muscle of the LV to inject 100 million cells into an average of 15 sites that showed damage on the electromechanical mapping of the heart. Perin said the procedure is relatively fast and painless, and involves only an overnight stay at the hospital. The study used electromechanical mapping of the heart to measure the voltage in areas of the heart muscle and create a real-time image of the heart.
Patients’ bone marrow cells were also sent to a biorepository, where studies were conducted to examine the phenotypes and functional characteristics of the cells. Exploratory analysis revealed that patients aged 62 years or younger showed a significant effect of stem cell therapy when LVEF was assessed. Researchers observed a significant 2.7% difference in the change over time in LVEF between the bone marrow cell group and the placebo group. In patients younger than the median age, there was a significant change in LVEF. In this younger group, the difference in the change over time in LVEF between the bone marrow cell group and the placebo group was 4.7%.
FOCUS-CCTRN is one of three studies conducted by the Cardiovascular Cell Therapy Research Network. Perin said research into stem cell therapy for CVDs has only “scratched the surface.”
At a press conference, ACC president David R. Holmes, Jr., MD, said, “We have hints, we don’t have answers” about stem cell therapy in this patient population. – by Katie Kalvaitis
For more information:
- Perin EC. Opening showcase and late-breaking clinical trials. Presented at: the American College of Cardiology 61st Scientific Sessions & Expo; March 24-27, 2012; Chicago.
- Perin EC. JAMA. 2012;doi:10.1001/jama.2012.418.
Disclosure: Dr. Perin reports no relevant financial disclosures. This study was funded by the National Heart, Lung and Blood Institute.
It is an important step to try to understand how to best use the bone marrow [cells]. I believe there is tremendous potential for bone marrow to become clinically useful … but we still have an enormous amount of ignorance about what the bone marrow does and how it works. Now we are starting to understand, thanks to insights also provided by the FOCUS-CCTRN study, that bone marrow in one patient is quite different from bone marrow in another patient; the older the patient, the more incompetent the bone marrow becomes; comorbidities have an impact on function … and many other things we do not know about that affect the ability of bone marrow cells to produce new blood vessels that would help the heart. Clearly, giving bone marrow [cells] indiscriminately to everybody is not going to produce a global beneficial effect. The subanalysis that Emerson Perin [and colleagues] showed really gives us some tantalizing hints that we may be able to select our patients in which bone marrow transplantation is therapeutically beneficial.
– Roberto Bolli, MD
Chief of the Division of Cardiovascular Medicine
University of Louisville