Doubt Cast on Major Pradaxa Safety Study

A drug watchdog in Canada apparently has some questions about the reliability of a pre-market <"">Pradaxa clinical trial. According to a report from the New Zealand Sunday Star Times, the Therapeutics Initiative at the University of British Columbia claims its reanalysis of that clinical trial indicates that more study is needed before Pradaxa can be declared safe.

At issue is a study called RE-LY, which compared two doses of Pradaxa with conventionally administered and monitored warfarin. The study, which involved 18,000 people, was published in the journal, Lancet Neurology, last November. RE-LY purportedly found that Pradaxa would prevent more strokes and save more lives than warfarin. The study played a key role in garnering approval for Pradaxa in Canada and elsewhere.

But according to the Therapeutics Initiative, its reanalysis of RE-LY showed more people taking Pradaxa were experiencing myocardial infarctions or heart attacks. Those on Pradaxa also had more serious stomach bleeds compared to those treated with warfarin, the group said. Based on its findings, Pradaxa’s approval was “premature, pharmalogically irrational and unsafe for many patients,” the Therapeutics Initiative said.

According to the Sunday Star Times, in the U.S., the Food & Drug Administration (FDA) asked the RE-LY investigators to re-evaluate their data the “for possible underreporting of events” following the agency’s pre-market Pradaxa review. The reanalysis found scores of previously unidentified, sometimes serious adverse events that had not been part of the trial’s published outcomes data. According to a report from, the additional adverse events included strokes and transient ischemic attacks, other embolic events, instances of major bleeding, and silent heart attacks evident by electrocardiography. The RE-LY researchers asserted the missed events were not unexpected for a study of that size and did not lead to any changes in the results. But Aaron Tejani of the Therapeutics Initiative told heartwire that not knowing the total serious adverse events made it, among other things, impossible to gauge Pradaxa’s true risks.

Since the Therapeutics Initiative conducted its RE-LY reanalysis, more red flags have been raised about Pradaxa’s safety, particularly about its association with serious bleeding. In August, regulators in Japan – where the drug is sold as Prazaxa – told Boehringer Ingelheim to issue a warning for Pradaxa and potentially fatal bleeding after 81 of the almost 64,000 mainly elderly patients taking it there suffered heavy bleeding. According to Reuters, five of those patients died. The Japanese health ministry also said a lower dose may have to be given to certain patient groups, such as those over 70 or with kidney damage.

Recently, the drug has caused similar concerns in New Zealand, where scores of Pradaxa patients have experienced incidents of severe bleeding. According to the Sunday Star Times, 122 cases of side effects in Pradaxa patients have been reported to the Centre for Adverse Reactions Monitoring (CARM), of which two out of five involved bleeding. As of a month ago, CARM had been alerted to four deaths; however, it said none were caused by Pradaxa. A CARM official said the agency was aware of nine cases of avoidable bleeding that may have stemmed from a too-rapid introduction of Pradaxa following warfarin treatment, or because the victims had inadequate kidney function.

This entry was posted in Pharmaceuticals, Pradaxa. Bookmark the permalink.

© 2005-2019 Parker Waichman LLP ®. All Rights Reserved.