Pradaxa RE-LY Study: Was It Flawed?

Boehringer Ingelheim, the manufacturer of Pradaxa, conducted a clinical trial known as RE-LY to determine which anti-coagulant – Pradaxa or decades-old warfarin – and dose was most effective in reducing strokes and systemic embolism in patients with atrial fibrillation. The study of 18,000 patients found that 182 patients who took 110 mg regimen of Pradaxa suffered a stroke compared with 134 patients receiving the 150mg dose. According to the study, 199 patients taking Warfarin sustained a stroke. The results indicated that Pradaxa was a safer, effective and easier-to-use alternative to warfarin, and allowed Boehringer Ingelheim to submit the drug for approval on the basis of these positive trial results.

Errors in the Clinical Trial?

Researchers from the University of British Columbia expressed that the RE-LY study was fundamentally flawed.

According to a letter published in the Therapeutics Initiative, researchers from the University of British Columbia expressed that the RE-LY study was fundamentally flawed. The researchers implied that the drug should have never received FDA-approval based on the results of the study and was prematurely introduced into the marketplace. According to their claims, the clinical trial used a double-blind method comparison between the two Pradaxa doses, but a non-blinding comparison between Pradaxa and warfarin. This allowed bias and errors to creep into the study’s results, the researchers claim. They urged that an independent audit of the study be performed to examine this bias, as well as irregularities in conduct and some of the trial’s findings. According to the researchers, Pradaxa is unsafe for many patients.

Other Findings in Pradaxa Study

Aside from questions surrounding the results of the Pradaxa RE-LY study, the research itself noted several concerns surrounding the drug. The patients receiving Pradaxa had a higher incidence of heart attacks than the warfarin subjects and exhibited a higher rate of major gastrointestinal bleeds. Furthermore, the study noted a number of other safety concerns related to use of the drug including excess dyspepsia and a potential for a higher-than-normal accumulation of the drug in patients with pre-existing kidney or liver problems.

More Safety Concerns Surrounding Pradaxa

Approximately a year and a half after Pradaxa received FDA approval based on this study, a group of hematologists in New Zealand expressed concerns over the drug’s bleeding risk. The hematologists wrote a letter published in the New England Journal of Medicine stating that a two-month review found 78 bleeding episodes, including a dozen major events in patients treated with Pradaxa. Many of the bleeding episodes involved the elderly and those with impaired renal function.

The hematologists expressed that the consequences of the drug’s lack of a reversal agent should not be underestimated and called for better prescriber education. Unlike warfarin, to which Pradaxa was compared in the RE-LY study, Pradaxa lacks a simple and effective antidote to counteract its anti-clotting effects. Therefore, when a Pradaxa user suffers even minor trauma, in a fall or other event, a small hemorrhage or bleed can progress extensively, unable to be controlled or even stopped.