Clinical Trials

Date: 2011-05-25

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the 20th European Stroke Conference

Company: Bayer (Germany)

Product: rivaroxaban

Action mechanism: oral anticoagulant

Disease: prevention of recurrent strokes in patients with atrial fibrillation

Therapeutic area: Cardiovascular diseases - Cerebrovascular diseases

Country:

Trial details:

• 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 an event-driven, prospective, randomized, double-blind Phase III study in which more than 14,000 patients were enrolled from more than 1,100 centers across 45 countries worldwide. The study’s primary goal was to assess the benefits of rivaroxaban 20mg once daily (or 15mg in patients with moderate renal impairment) in comparison with dose-adjusted warfarin in the protection of patients with non-valvular AF from stroke and non-CNS systemic embolism. The primary efficacy endpoint was a composite of all-cause stroke and non-CNS systemic embolism. The principal safety outcome was a composite of major and non-major clinically relevant bleeding events. The study met its primary endpoint of establishing non-inferiority of once-daily rivaroxaban versus warfarin whilst demonstrating a comparable safety profile. In the pre-specified primary efficacy analysis in the safety population while on treatment, rivaroxaban was superior to warfarin for prevention of stroke and systemic embolism. In an additional analysis in the intent-to-treat population to site notification, following all patients randomized in the trial whether or not they completed the course of therapy until the end of the trial was announced, rivaroxaban showed comparable efficacy to warfarin.

Latest news:

• A pre-planned subgroup analysis of the ROCKET AF Phase III clinical study confirms that rivaroxaban is highly effective in the prevention of recurrent strokes in patients with atrial fibrillation (AF) who have experienced a prior stroke or transient ischemic attack (TIA). These findings were presented at the 20th European Stroke Conference by Professor Werner Hacke, Chair of the Department of Neurology at the University of Heidelberg, Germany, and member of the ROCKET AF Executive Steering Committee. The ROCKET AF secondary prevention sub-analysis examined the benefits of rivaroxaban and warfarin in the highest number of prior-stroke AF patients studied to date (7,468 total patients). Rivaroxaban showed a numerically lower (13%) risk compared with warfarin in the combined endpoint of stroke and systemic embolism in this subgroup of patients, this being in line with the results of the main ROCKET AF trial. Overall bleeding rates were similar between both treatment arms, although fatal bleeding events, as well as ICH events, were less frequent in those receiving rivaroxaban. Overall, the benefit-risk profile favours rivaroxaban in these difficult to manage secondary prevention patients. These differences did not reach statistical significance as this subgroup analysis was not powered for these endpoints. The investigators concluded that rivaroxaban is an effective alternative to warfarin for the protection of patients from both a first and recurrent strokes.
• The secondary prevention subgroup of the ROCKET AF study, consisting of patients with a prior history of stroke or TIA (representing 55 per cent of the total study population), received either 20mg once daily rivaroxaban (or 15 mg for patients with moderate renal impairment), or dose-adjusted warfarin. The ROCKET AF principal safety outcome was major and non-major clinically relevant bleeding. Rivaroxaban showed a numerically lower (13%) risk compared to warfarin in the prevention of recurrent strokes or non-CNS embolism in the safety population while on-treatment (2.26 events per 100 patient-years for rivaroxaban and 2.60 events per 100 patient-years for warfarin, HR 0.87, 95% CI [0.69, 1.10]). Similar rates of overall bleeding to those seen in the primary ROCKET AF analysis were found, with no difference between the treatment groups (13.31 safety outcome-related events per 100 patient-years for rivaroxaban and 13.87 events per 100 patient-years for warfarin, HR 0.96, 95% CI [0.87, 1.07]). Rates of ICH were numerically lower in the rivaroxaban arm (0.59 events per 100 patient-years for rivaroxaban and 0.8 events per 100 patient-years for warfarin, HR 0.74, 95% CI [0.47, 1.15]).

Is general: Yes