12/20/18: NHLBI update on next steps for CONCERT-HF
Administration of study products or placebo may proceed for participants who already underwent tissue collection. Recruitment of new participants remains paused.
After pausing the CONCERT-HF trial to allow for an independent re-assessment by the study’s Data and Safety Monitoring Board (DSMB), the NHLBI has authorized the investigators to proceed with administration of study products to those participants who have already undergone tissue collection procedures.
The DSMB met on November 30, 2018 and was charged with conducting a re-assessment of the scientific foundations of the trial and to ensure that it continues to meet the highest standards for participant safety and scientific validity. They reviewed the scientific literature and detailed information and reports submitted by CONCERT-HF investigators, and concluded that the scientific basis and rationale for the CONCERT-HF trial was sound, that the cell products met the criteria for clinical use, and that there were no new concerns related to participant safety. Additionally, the DSMB recommended modifications to the CONCERT-HF protocol and informed consent form to reflect the updated assessment of the state of the science and published literature. In light of these findings, the DSMB recommended allowing the administration of study products to the participants already enrolled who have had tissue collected for production of cell-based products.
The NHLBI accepted and authorized implementation of the DSMB’s recommendations on December 8, 2018. After the Institutional Review Boards at the participating clinical sites have completed their review of these recommendations, participants will be notified regarding receipt of study products.
NHLBI will make a final decision as to whether the CONCERT-HF trial should resume enrollment of new participants after consideration of a scheduled interim analysis of the trial results and further input from the DSMB. In the meantime, enrollment of new participants remains paused.
Statement on NHLBI decision to pause the CONCERT-HF trial
October 29, 2018
The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is pausing the CONCERT-HF trial, which involves patients with chronic heart failure. Recent calls for the retraction of journal articles in related fields of cell therapy research have raised concerns about the scientific foundations of this trial. While none of the articles in question derive from the CONCERT-HF trial itself, the NHLBI convened CONCERT-HF’s Data and Safety Monitoring Board (DSMB) out of an abundance of caution to ensure the study continues to meet the highest standards for participant safety and scientific integrity. Informed by the DSMB recommendations of October 25, 2018, the NHLBI is pausing the trial. While the DSMB did not have any participant safety concerns, this pause enables the DSMB to complete its review.
The safety of all clinical trial participants is paramount to NHLBI. NHLBI will honor its commitment to CONCERT-HF participants and continue the follow-up protocol during this pause for all participants who have already been treated in the study. Participants are being notified of the status of the trial and how to request additional information.
The CONCERT-HF trial seeks to determine whether c-kit+ cells, either alone or in combination with mesenchymal stem cells derived from the bone marrow, are safe and benefit patients with chronic heart failure, who have very limited treatment options. Despite significant medical and surgical advances, patients with heart failure continue to experience a low quality of life and about half of them will die within five years of receiving a diagnosis.
The scientific basis of CONCERT-HF is supported by a body of evidence in several preclinical models in a number of studies in a variety of laboratories and was reviewed by a Protocol Review Committee (PRC) independent of the trial. The cell therapies that CONCERT-HF is testing are under an investigational new drug (IND) designation which is overseen by the U.S. Food and Drug Administration (FDA). The cells are produced by an accredited laboratory independent of the clinical sites. In addition, as part of standard oversight of clinical trials, the DSMB routinely reviews and monitors CONCERT-HF to ensure participant safety and that the study continues to ask compelling scientific questions with implications for patient care.
The DSMB's review will be conducted as expeditiously as possible and will inform NHLBI’s future actions that will ensure the highest standards of participant safety and scientific integrity.