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RENEW: Cell therapy for refractory angina shows promise despite cessation of trial
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ORLANDO, Fla. — A cell therapy to treat patients with refractory angina showed positive outcomes in a trial that was truncated by its sponsor, researchers reported at the Society for Cardiovascular Angiography and Interventions Scientific Sessions.
The RENEW pivotal study was designed to enroll 444 patients with refractory angina who were on maximal angina therapy, had evidence of ischemia and were not candidates for revascularization.
The goal was to have approximately 200 evaluable patients randomly assigned granulocyte colony-stimulating factor (G-CSF) mobilized CD34+ cells, approximately 100 evaluable patients assigned placebo injections and approximately 100 evaluable patients assigned standard care, Timothy D. Henry, MD, interventional cardiologist and director of cardiology at Cedars-Sinai Heart Institute, said during a press conference.
Timothy D. Henry
However, he said, “the trial was stopped in December 2013 by the sponsor [Baxter], not because of safety or efficacy, but because of strategic and financial decisions by the company.”
Before the trial was stopped, researchers had enrolled 112 patients: 57 in the CD34+ group, 27 in the placebo group and 28 in the standard-care group. The standard-care group was unblinded, and its existence may have discouraged patients from enrolling, Henry said.
“The trial was working very well and enrollment was proceeding very well,” he said. “After Baxter made its decision, we tried in the midst of the trial to find alternative sponsors, and there was definite interest.”
The primary outcome was change in exercise time between the CD34+ group and the placebo group. Other outcomes of interest were angina frequency and mortality.
When the trial was stopped, exercise time improved approximately 1 minute more in the CD34+ group than in the placebo group at 6 months and in excess of 30 seconds more at 12 months, Henry said.
Angina frequency was decreased at 6 months in the CD34+ group compared with the placebo group (RR = 0.57; 95% CI, 0.36-0.92), according to the researchers.
At 2 years, the mortality rate was 3.7% in the CD34+ group, 7.1% in the standard-care group and 10% in the placebo group.
MACE at 2 years was “very high” at 67.9% in the standard-care group, Henry said, but similar in the CD34+ group (46%) and the placebo group (47.9%).
“The utility of CD34+ cells for refractory angina still looks very promising, but unfortunately we still don’t have an adequately powered phase 3 trial,” Henry said. “I would call RENEW an opportunity lost.”
Thomas J. Povsic, MD, of Duke Clinical Research Institute and co-principal investigator of the study with Henry, noted that patients with refractory angina have not been studied in trials of other cell therapies.
Thomas J. Povsic
“We think it’s particularly attractive to use angiogenic cells in patients with refractory angina whose issue is lack of blood flow,” he said. “We hope someone else will take up the call. We did learn a lot from this trial. The standard-of-care arm did extremely poorly.”
Although the standard-care arm was included to meet regulatory requirements, “we hope that this experience will inform the design of future trials so that this type of burdensome design will not be required,” Povsic said. “Hopefully, that will allow us to run a better trial the next time around.”
The paper has been accepted for publication by JACC: Cardiovascular Interventions and will be published at a later date, Povsic said. – by Erik Swain
Reference:
Henry TD, et al. Late-Breaking Clinical Trials – Part 2. Presented at: Society for Cardiovascular Angiography and Interventions Scientific Sessions; May 4-7, 2016; Orlando, Fla.
Disclosure: The study was funded by Baxter. Henry reports receiving reimbursement from Baxter for expenses incurred in his role as co-principal investigator of the study.
Perspective
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John P. Reilly, MD
This is a frustrating patient population because we interventionalists feel that we can’t treat them. And the patients are very frustrated with their medical-treatment regimen, and many don’t want to have a surgical procedure for transmyocardial revascularization, for which efficacy in that group is inconclusive. I am hopeful that stem-cell or gene therapy will prove effective for these patients.
These do look like promising data, consistent with phase 2 studies that have been done. That was encouraging, and it’s unfortunate that the investigators did not get to complete the trial that they had set out and designed. We will somehow have to get more data before we can know whether cell therapy benefits patients with refractory angina.
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