By Bruce Sylvester
GENEVA, SWITZERLAND -- July 9, 2007 -- Results of a phase 2 study suggest that the investigative agent apixaban, an oral direct Factor Xa inhibitor, is efficacious as monotherapy in a fixed dose for patients with acute symptomatic deep vein thrombosis (DVT).
The findings were presented here on June 8th at the 21st Congress of the International Society on Thrombosis and Haemostasis (ISTH).
"Our findings indicate that this new agent could emerge as an effective monotherapy for treating acute symptomatic DVT," says presenter and investigator Harry Buller, MD, Professor of Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands. "Phase 3 studies are ongoing and we look forward to seeing the results."
The investigators randomised 520 subjects to one of three double-blind regimens of apixaban (5 mg BID; 10 mg BID; 20 mg QD) or conventional treatment with low-molecular-weight heparin or fondaparinux followed by open-label vitamin K antagonist dose-adjusted to an International Normalised Ratio of 2.0 to 3.0.
Subjects were treated for 84 to 91 days.
All patients were evaluated using bilateral venous compression ultrasound (CUS) of the legs and perfusion lung scan (PLS) within 36 hours of randomisation and at 12 weeks.
The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism (VTE) and deterioration of the thrombosis burden as indicated by comparison of baseline and endpoint bilateral CUS and PLS.
The principal safety outcome was a composite of major and clinically relevant nonmajor bleeding. A central, independent, and blinded adjudication committee (CIAC) evaluated all outcomes.
For apixaban 5 mg BID, 10 mg BID, 20 mg QD, and for vitamin K antagonist, the primary efficacy outcome rates were 6.0%, 5.6%, 2.6%, and 4.2%, respectively, and the principal safety outcome rates were 8.6%, 4.5%, 7.3%, and 7.9%, respectively. Rates of symptomatic VTE were 2.6%, 3.2%, 1.7%, and 2.5%, respectively, and rates of major bleeding were 0.8%, 0, 0.8%, and 0, respectively.
"This oral direct Factor Xa inhibitor that can be given as the sole treatment in a fixed dose appears to be a very attractive alternative to standard therapy in patients with DVT," the authors conclude.
The research was supported by Bristol-Myers Squibb.
[Presentation title: Late Breaking Clinical Trial: A Dose Finding Study of the Oral Direct Factor Xa Inhibitor Apixaban in the Treatment of Patients With Acute Symptomatic Deep Vein Thrombosis - The Botticelli Investigators. O-S-003]
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