CHICAGO—Cardiologists wrangled over whether or not the findings of the FOCUS trial, despite its inability to reach the pre-established primary endpoint actually indicates promise for the future of cell therapy in patients with ischemic heart disease that do not have another therapeutic options. The trial was presented March 24 at the American College of Cardiology’s (ACC) 61st annual scientific session.
The trial is conducted by the Cardiovascular Cell Therapy Research Network (CCTRN), which was developed by the National Heart, Lung and Blood Institute to advance cell therapy for patients with cardiovascular diseases by using a collaborative network approach to facilitate larger studies with wide applicability.
In the Journal of the American Medical Association, where the trial was simultaneously published, the researchers wrote, “The FOCUS-CCTRN trial is the first, to our knowledge, adequately powered study of cell therapy in patients with chronic ischemic heart disease and LV [left ventricular] dysfunction (LVEF <45 percent) to be completed in the United States.”
Emerson C. Perin, MD, PhD, from Texas Heart Institute in Houston, and his CCTRN colleagues conducted this double blinded, randomized, multicenter trial for the transendocardial delivery of a dose of 100 million autologous bone marrow mononuclear cells (BMCs) in patients with chronic ischemic heart disease and LV dysfunction with heart failure and/or angina.
As their three primary endpoints, the researchers selected a change in maximum oxygen consumption (MVO2); a change in LV end-systolic volume (LVESV) as assessed by echocardiography; and a change in ischemic (reversible) defect size as assessed by SPECT. The secondary endpoints were Wall motion by echocardiography; a change in LV end-diastolic volume (LVEDV) as assessed by echocardiography; a change in total and fixed defect size as assessed by SPECT; and a change in functional class (NYHA,CCS) and serum BNP levels.
Between April 2009 and 2011, researchers at five sites randomly selected 92 patients to receive stem cell treatment or placebo (61 patients received BMCs, compared with 31 that received placebo). The patients, average age 63, all had chronic ischemic heart disease and an ejection fraction of less than 45 percent along with heart failure and/or angina and were no longer candidates for revascularization.
Researchers found that LVEF increased by a small but significant amount (2.7 percent) in patients who received stem cell therapy. The study also revealed that the improvement in ejection fraction correlated with the number of CD34+ and CD133+ cells in the bone marrow—information that will be helpful in evaluating and designing future therapies and trials, according to the researchers.
However, based on the original study primary endpoints, there were no significant differences at baseline and at six months. “If we had picked an endpoint of LVEF, we would have had a positive study,” Perin said during his presentation. “This is a very sick population for whom we have no available treatments, and the ongoing stem cell therapy research could provide us with an option.”
While all the study discussants deemed the trial “very important,” some were hesitant to accept the researchers’ positive interpretation of the results. Namely, Robert M. Califf, MD, of Duke University Health System in Durham, N.C., who even questioned the study’s classification as a Phase II study rather than a Phase I study due to its small size, classified FOCUS as “a resoundingly negative study, not just a somewhat negative study. Of the three primary endpoints, there was did not scintilla of positively in the findings.”
“Based on this trial, we don’t have answers, but we have hints at what’s to come,” concluded ACC President David R. Holmes, Jr., MD.