Xarelto Blood Testing Problems During Clinical Trials May Have Compromised Approval Process

Federal regulators are reportedly taking a close look at the clinical trials used to gain FDA approval for Xarelto, following concerns that a faulty blood monitor used during those studies may have provided inaccurate results about the safety of the controversial blood thinner, which has since been linked to thousands of reports involving uncontrollable bleeding and death. 

According to a report published by the New York Times on Monday, a legal brief filed in the pending litigation over side effects of Xarelto indicates that the FDA is investigating issues during the clinical trials known as ROCKET-AF.

The investigation is focusing on the use of a device to measure the levels of the older blood thinner warfarin in test subjects’ blood, which is now believed to have been defective and may have compromised the approval process for the medication that has been promoted as a superior alternative.

The clinical trial blood testing problems were first reported in the medical journal The BMJ in December, with researchers warning that the device may have led to an underestimation of the rate of Xarelto bleeding complications.

The device, the INRatio, by Alere, was used in the ROCKET-AF clinical trials, which compared the rate of bleeding events between Xarelto (rivaroxaban) and Coumadin (warfarin). The device measured the levels of warfarin in patients’ blood and was used to adjust their dosage. However, in December 2014, there was an INRatio recall after it was discovered that some of the devices could return results that were falsely low. The recall came after Alere received nearly 19,000 reports of malfunctions, 14 of which resulted in serious injuries.

The recall could affect the ROCKET-AF results, because falsely low readings could have resulted in warfarin patients being given too high a dose, increasing their risk of bleeding. If the device caused excessive bleeding among warfarin patients, it could have given the false impression that Xarelto had a lower rate of bleeding problems.

According to the New York Times article, the FDA has questioned Johnson & Johnson in detail over the device, and about whether they had any indication that the one they were using might have been a defective unit.

The clinical trials, led by Dr. Robert Califf, who has been nominated to become the FDA commissioner, have come under intense criticism for a variety of reasons since Xarelto was approved and linked to a shocking number of reports involving bleeding problems that doctors were hard-pressed to stop, often resulting in severe injury or death.

Xarelto (rivaroxaban) is part of a new class of blood thinners introduced in recent years as a replacement for warfarin, which has been the go-to anticoagulation treatment for decades. Since it was approved in 2011, this new-generation treatment has been commonly prescribed instead of warfarin for reduction of the risk of blood clots and strokes among patients with atrial fibrillation, or following hip or knee replacement surgery.

There are currently more than 4,000 Xarelto lawsuits pending in courts throughout the U.S., alleging that the drug maker failed to adequately warn consumers or the medical community about the risk of uncontrollable bleeding linked to the medication

While users of warfarin can be given a dose of vitamin K to reduce the blood thinning effects of the medication, there were no similar reversal agents available for Xarelto at the time it was introduced, placing doctors in a position where they were unable to control many bleeding problems.

Lawsuits also allege that the drug makers provided false and misleading information about the importance of blood monitoring on Xarelto, marketing the drug as easier to use and indicating that it does not require close testing like warfarin. However, independent studies published after the medication was introduced have suggested that Xarelto monitoring may help identify patients at greater risk of bleeds.

The legal brief filed this week comes as the parties are preparing a small group of cases for early trial dates, known as “bellwether” lawsuits, which are expected to go before federal juries early next year. While the outcome of these test trials will not be binding in other lawsuits, they may help the parties negotiate Xarelto settlements to avoid the need for hundreds of individual trials throughout the U.S.