AleCardio Trial Halted for Safety and Efficacy in July; Drug Increased Serious Risks of Bone Fractures, Heart Failure, Renal Dysfunction, and Bleeding
Sunday, March 30, 2014
The experimental drug aleglitazar did not decrease the risk of cardiovascular death, heart attack, or stroke in patients with acute coronary syndrome and type 2 diabetes, according to research from the Cleveland Clinic Coordinating Center for Clinical Research (C5Research). In addition, data from the AleCardio trial show that patients treated with aleglitazar were at an increased risk of bone fractures, gastrointestinal bleeding, heart failure, and kidney dysfunction.
The AleCardio trial was halted in July 2013 for safety and efficacy after a review by the trial’s independent Data Safety Monitoring Board. The full data from the trial is being presented today at the American College of Cardiology Scientific Sessions in Washington, D.C., by A. Michael Lincoff, MD, director of C5Research and Vice Chairman of Cardiovascular Medicine at Cleveland Clinic, and simultaneously published online in the Journal of the American Medical Association.
Aleglitazar is part of a class of drugs called dual peroxisome proliferator-activated receptor (PPAR) agonists, which are being studied for their effect on both cholesterol levels and insulin sensitivity in patients with diabetes.
AleCardio was designed to determine whether the addition of aleglitazar to standard of care in patients with type 2 diabetes would reduce the risk of cardiovascular events following a recent incident of acute coronary syndrome. Patients with acute coronary syndrome have had a heart attack or experienced unstable angina, which can lead to a heart attack.
Prior to the trial’s termination, 7,226 patients were enrolled at 720 hospitals in 26 countries, and randomized equally into the aleglitazar or placebo arms. The primary endpoint of cardiovascular death, heart attack, or stroke occurred in 9.5 percent of patients on aleglitazar and 10 percent of patients in the placebo group. The drug did have a positive effect on blood sugar and lipid levels, but it was not found to reduce cardiovascular mortality or morbidity. Further, the researchers found that the drug increased the serious risks of heart failure, renal dysfunction, hypoglycemia, bone fractures, and gastrointestinal bleeding.
“Despite aleglitazar’s positive impact on sugar and lipid levels, it didn’t translate into a decrease in risk of cardiovascular death, heart attack, or stroke,” said Dr. Lincoff, the lead investigator on the AleCardio trial. “This result is indicative of the difficulties associated with the development of this class of drugs, which often have complex metabolic outcomes and unpredictable therapeutic profiles. More research must be done to find a way to reduce the burden of heart disease in patients with diabetes.”
AleCardio was a Phase III, multicenter, randomized, double-blind, placebo-controlled trial sponsored by F. Hoffmann-La Roche Ltd., which had a role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; and the review of the manuscript. An executive steering committee – consisting of academic members and two non-voting representatives from the sponsoring company – designed the trial and was responsible for its conduct. The trial’s Data Safety Monitoring Board, consisting of independent physicians and statisticians, had access to the unblinded data and monitored the safety of the study.
Dr. Lincoff, through Cleveland Clinic, has received research grants from AstraZeneca, CSL Limited, Eli Lilly, Regado Biosciences, Roche, Takeda, and Vivus.
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