"This new oral agent interacts directly with factor Xa, eliminating the need for anti-thrombin III, a common target in the coagulation pathway for most antithrombotic drugs," said Michael Rud Lassen, M.D., of Hoersholm Hospital, Denmark, lead investigator of the study. "Razaxaban shows future promise as an additive drug and may help to reduce thrombosis in patients undergoing major orthopedic surgery."

Patients undergoing elective primary total knee replacement surgery were randomly assigned to one of four dose groups for razaxaban (25 mg, 50 mg, 75 mg, or 100 mg bid) or enoxaparin (30 mg administered subcutaneously bid). Treatment with razaxaban started eight hours after surgery and standard therapy was started 12 to 24 hours after surgery. Treatment was continued for 10 days and then venography (radiographic demonstration of a vein after the administration of a contrast agent) of both legs was performed to see whether clots had developed in the veins.

The primary efficacy outcome of this study measured the incidence of a venous thromboembolism during treatment. The safety analysis measured all bleeding incidents (major and non-major), thrombocytopenia (decrease in the number of platelets), and death. An independent medical committee that was unaware of treatment assignment determined the incidence of all events.

Of the 656 patients treated and included in the safety analysis, 438 were eligible for efficacy analysis. Efficacy results showed a dose-dependent relationship; patients taking razaxaban had a lower rate of venous thromboembolism than those with standard therapy (8.6 percent - 25 mg bid; 6.0 percent - 50 mg bid; 3.6 percent - 75 mg bid; and 1.4 percent - 100 mg bid versus 15.9 percent - enoxaparin 30 mg bid). Safety results showed an opposite dose-dependent relationship. Patients on the higher doses of razaxaban s
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Contact: Aimee Frank
amf@spectrumscience.com
202-955-6222
American Society of Hematology
6-Dec-2003