February 3, 2016 – The results of a re-analysis of the ROCKET AF trial were published recently in The New England Journal of Medicine.
As announced previously, the ROCKET AF Executive Committee initiated a re-analysis of the ROCKET AF trial in October 2015, immediately after learning of the U.S. Food and Drug Administration recall of the Alere INRatio and INRatio2 PT/INR Monitor device used in the trial. The purpose of the re-analysis was to determine what effect, if any, the possible malfunctioning of the device may have had on the original trial’s conclusions. The device recall occurred in 2014, four years after the trial’s completion.
The results of the re-analysis confirm the original study’s finding that the anticoagulant rivaroxaban is noninferior to warfarin for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and additional stroke risk factors, and its use is associated with less bleeding. The re-analysis found that any possible malfunction of the device that could have led to lower INR measures than laboratory testing did not have any significant clinical effect on the primary efficacy and safety outcome measures recorded in the ROCKET AF trial. The results among patients with no conditions and among patients with any condition possibly affecting device function were consistent with the results of the overall trial population and with each other.
The re-analysis by the Executive Committee is separate from, and in addition to, the study sponsor’s analysis, which has been provided to U.S. and European regulatory agencies. The results of the Executive Committee’s re-analysis have undergone peer review and statistical review and appear as a research letter in the online edition of the New England Journal of Medicine. The Executive Committee has worked diligently to conduct the re-analysis and to get a peer-reviewed research letter into the public domain as quickly as possible and will continue to discuss options for additional analysis of the data, including review and replication by other groups.
ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was a multicenter, randomized, double-blind, trial that compared rivaroxaban with warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation and at increased risk for stroke. The trial was conducted at 1,178 sites in 45 countries.