What is the CONCERT-HF study?
The CONCERT-HF study launched in 2015 and is funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). This study seeks to determine whether cardiac stem cells (CSCs), either alone or in combination with mesenchymal stem cells (MSCs) derived from the bone marrow, are safe for and beneficial to people who have chronic heart failure. Despite significant medical and surgical advances, people who have chronic heart failure have very limited treatment options. As a result, they continue to experience a low quality of life, and about half will die within five years of receiving a diagnosis.
How was the CONCERT-HF study designed?
CONCERT-HF was designed as a randomized, double-blind, placebo-controlled phase II trial to enroll 144 participants from seven centers in the United States. Participants were randomly selected to receive one of four treatments: CSCs and MSCs together, CSCs alone, MSCs alone, or placebo.
Participants had tissue samples collected from their heart and bone marrow to prepare the cell-based products. These products or placebo are injected directly into each participant’s heart via a catheter. Each participant then will have regular follow-up visits—after one day, one week, one month, three months, six months, and 12 months. Tests performed during these visits will determine how the treatments may have affected the heart’s ability to pump blood.
Why was the CONCERT-HF study paused?
Calls for the retraction of journal articles in related fields of cell therapy research prompted concerns about the safety and scientific foundations of the CONCERT-HF study. While none of the articles in question derives from the CONCERT-HF trial itself, out of an abundance of caution the NHLBI sought guidance from CONCERT-HF’s Data and Safety Monitoring Board (DSMB). The DSMB is an independent group of experts that periodically reviews and evaluates study data and makes recommendations to the NHLBI regarding participant safety, data integrity, and study progress. Based on their recommendation, the NHLBI paused the study on October 29, 2018, so that the safety and scientific validity of CONCERT-HF could be re-evaluated.
What has happened since the study was paused?
The DSMB met on November 30, 2018, to review the scientific literature, detailed information, and reports submitted by the CONCERT-HF investigators. They concluded that the scientific basis and rationale for the CONCERT-HF study were sound, that the cell-based products administered to participants met the criteria for clinical use, and that there were no concerns related to participant safety. Therefore, the DSMB recommended that the study continue for those participants whose tissue had been collected already.
The DSMB met again on February 6, 2019, to review a more detailed report on the cell-based product manufacturing process prepared by an Independent External Expert Panel (IEEP), and to evaluate an interim analysis of study results. In light of the IEEP report, the DSMB concluded that the CONCERT-HF cell product be deemed acceptable for clinical administration to participants.
Based on the interim analysis, the DSMB determined that the data collected from the participants currently enrolled in the study who have already undergone tissue collection will likely provide sufficient information to answer the key study questions with rigor. The NHLBI accepted these recommendations.
What is the current status of the study?
At a regularly scheduled meeting on March 8, 2019, the DSMB had no actionable safety concerns and recommended that the study continue. Additionally, the DSMB recommended submission of another interim analysis that included 12-month efficacy and safety data. NHLBI accepted these recommendations.
At a regularly scheduled meeting on September 13, 2019, the DSMB reviewed the requested interim analysis report and recommended that the study continue. Additionally, the DSMB recommended removal of the pause on recruitment. NHLBI accepted these recommendations and determined that the study should continue without additional recruitment.