FDA Backs Xarelto Safety After Analyses on Faulty Device Used in Trial
FDA says that internal analyses on the use of Alere’s faulty blood testing devices (INRatio and INRatio 2 PT/INR) had a “minimal” impact on a clinical trial involving Johnson & Johnson’s blood thinner Xarelto. “The agency has determined that effects on strokes or bleeding, including bleeding in the head, were minimal,” an FDA notice says. “The FDA concludes that Xarelto is a safe and effective alternative to warfarin in patients with atrial fibrillation.”
In July, INRatio devices were recalled due to the potential to generate inaccurate results (see story). The devices were used to monitor warfarin therapy in the control group of the ROCKET-AF clinical trial, which provided the primary data to support Xarelto’s 2011 approval for reducing the rates of stroke and blood clots in patients with non-valvular atrial fibrillation.
Last year, Public Citizen reported that the blood testing devices used in the trial, which was overseen by a steering committee chaired by FDA commissioner Robert Califf when he was at the Duke Clinical Research Institute, had been the subject of 9,469 malfunction reports and 1,445 injury reports since their original marketing in 2002. “The new data about the INRatio device’s inaccurate measurements and safety raise questions about Califf’s participation in the decision to use it in the trial, called ROCKET AF, which was started more than nine years ago and funded by Johnson & Johnson,” the advocacy group said. “False readings by the blood testing device could have skewed the trial results” in favor of Xarelto.
In concluding its analyses, FDA says data it reviewed indicate that “it is quite likely that patients in the warfarin arm of ROCKET unintentionally received higher doses of warfarin than they would have received if the INRatio device had provided results similar to those provided by the laboratory-based device at Duke. However, the effects of this increased intensity of anticoagulation on clinical outcomes were likely to have been quite modest. It seems very unlikely that if the device had performed similarly to the INR assessment device at Duke, the benefit/risk profile of rivaroxaban compared to warfarin would have been notably different from the profile based on the observed results of ROCKET. Accordingly, the conclusion we made in 2011 that the benefits of rivaroxaban in patients with non-valvular atrial fibrillation outweigh its risks should not be changed.”