(Exanta / AZN) Lancet Publishes Results of Largest Stroke Prevention Trial; AstraZeneca's Investigational Oral Anticoagulant Studied as Alternative to Well-Controlled Warfarin for Stroke Prevention in Atrial Fibrillation
Thursday November 20, 6:30 pm ET
WILMINGTON, Del., Nov. 20 /PRNewswire-FirstCall/ -- Results of the largest stroke prevention trial ever conducted comparing AstraZeneca's investigational oral anticoagulant EXANTA(TM) (ximelagatran) to warfarin in patients with nonvalvular atrial fibrillation (NVAF) were published today in The Lancet.
SPORTIF III (Stroke Prevention using an ORal Thrombin Inhibitor in atrial Fibrillation) was an open-label, randomized, non-inferiority trial. In the intent-to-treat analysis, patients treated with EXANTA (n=1,704) had 40 strokes and systemic embolic events compared to 56 events in patients treated with warfarin (n=1,703). This difference was not statistically different and, thus, this non-inferiority trial achieved its primary endpoint. An analysis of results restricted to the time patients took the study drug showed the patients receiving EXANTA had 29 strokes and systemic embolic events compared to 52 events for patients on warfarin, a statistically significant relative risk reduction of 41 percent (p=0.018).
SPORTIF III was conducted in 3,407 patients in 23 countries in Europe, Asia, Australia and New Zealand. In the study, 1,704 patients with NVAF and at least one additional stroke risk factor received fixed-dose EXANTA (36 mg BID) and 1,703 patients received warfarin (dose-adjusted to an INR of 2-3). The SPORTIF program enrolled both newly treated patients and patients that were already on warfarin therapy. Patients were treated for a mean duration of 17.4 months. Warfarin was well controlled in the study with 66 percent of INR measurements between 2.0 and 3.0.
In the trial, there were 29 major bleeding events in the group receiving EXANTA compared to 41 in the warfarin arm (p=ns). The incidence of total bleeding events (major and minor bleeding) was 25.8% per year with EXANTA compared to 29.8% per year with warfarin (p=0.007). Additionally, 6.3 percent of patients treated with EXANTA experienced an increase to greater than three times the upper limit of normal of the liver enzyme alanine aminotransferase (ALT), compared to 0.8 percent of patients in the warfarin group. Nearly all enzyme changes occurred within the first six months of treatment and decreased with or without drug discontinuation.
SPORTIF III is one of two Phase III trials of the SPORTIF program. The SPORTIF program includes 7,329 patients. Results of the North American part of the program, SPORTIF V, which includes 3,922 patients at 409 sites, were presented at the American Heart Association 2003 Scientific Sessions on November 11.
ABOUT EXANTA
Phase III studies with EXANTA have been completed in a number of indications, and approximately 30,000 patients have been enrolled to date in the clinical trial program for EXANTA. EXANTA is the first oral anticoagulant to reach late-stage clinical trials since the development of warfarin 50 years ago. Regulatory submission for the initial indications of stroke prevention in atrial fibrillation, prophylaxis of venous thromboembolism (VTE) in patients undergoing total knee replacement surgery, and long-term secondary prevention of VTE remain on track for late 2003.
The proposed mechanism of action of EXANTA is to inhibit the activity of an enzyme called thrombin, which is critical to the final step in the formation of blood clots. Clinical studies with EXANTA utilized a fixed dose without routine coagulation monitoring.... |
