Government Intervenes in Heart Study Following Concerns About Underlying Research

A government agency has paused a clinical trial testing an experimental stem cell therapy in heart failure patients, a move made public on Monday and sparked by recommendations to retract 31 journal articles from the lab of a controversial cardiac stem cell researcher.

“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,” the National Heart, Lung, and Blood Institute said in a statement posted Monday.

On Oct. 17, the New England Journal of Medicine retracted one paper and published an “expression of concern” about two others from the lab of Dr. Piero Anversa, a controversial stem cell researcher. The journal’s move came three days after Harvard Medical School and Brigham and Women’s Hospital told STAT and Retraction Watch they had recommended that 31 papers from Anversa be retracted by medical journals.

Dr. David Goff, director of the Division of Cardiovascular Sciences at NHLBI, confirmed Monday that news about the 31 journal articles from the Anversa lab prompted the pause in the trial known as CONCERT-HF. None of the retracted or disputed papers specifically relate to the trial, he said, but the trial’s Data and Safety Monitoring Board, convened last week at the institute’s request, on Friday recommended a “pause” in the trial so the board could complete its review.

Anversa’s research focused on advancing the idea that the heart contains stem cells, called c-kit cells, that could regenerate cardiac muscle after a heart attack. But when various research teams tried to reproduce results reported in his papers, they failed. Anversa left Harvard and the Brigham in 2015. Lawyers for Anversa and his colleague Dr. Annarosa Leri said earlier this month the doctors “stand by the scientific findings in their papers, including the existence and potential therapeutic benefits of cardiac stem cells.” In an Oct. 3 letter that Anversa provided to The New York Times, Harvard and the Brigham said he had “committed research misconduct” in eight papers and in a grant application.

The CONCERT-HF study set out to determine whether c-kit+ cells, either alone or in combination with stem cells derived from the bone marrow, are safe and could help patients with chronic heart failure. There are limited treatment options for people with heart failure; half of them will die within five years of receiving a diagnosis.

Goff said that the study’s approval to launch in 2015 was based on 11 reports from eight different labs — all independent of Anversa’s — showing benefits from c-kit+ cells in animal experiments. At the time, reviewers of the study protocols were aware that other labs were unable to duplicate findings reported by Anversa and his colleagues.

The University of Texas and NHLBI are sponsors of the trial, which sought to enroll 141 patients at seven locations since it was launched in 2015. The trial has recruited 125 patients, Goff said. Of those 125 people, 117 have undergone tissue collection from bone marrow or heart muscle and 90 have been treated.

Dr. Lem Moye of the University of Texas said participants are being notified about the trial’s pause and being told that recent media coverage about cell therapy research is not directly related to CONCERT-HF.

“Although we do not follow the protocols of Dr. Anversa (we have our own lab at the University of Miami which uses GMP procedures, as is FDA approved). … NHLBI would like to assure itself that our lab is in fact generating c-kit+ cells,” Moye wrote in response to questions. “We hope that this will not take long.”

Goff said NHLBI has asked the board to conduct an “expeditious review in keeping with appropriate rigor.”

“We have a responsibility to our participants and to generating knowledge to improve the health of people with heart failure.”