BACKGROUND:Vitamin K antagonists for secondary prevention in patients with deep vein thrombosis (DVT) require monitoring and dose adjustments. The synthetic factor Xa inhibitor, SanOrg34006, has predictable pharmacokinetics and may be administered once weekly without dose adjustments. METHODS: After 5-7 days of enoxaparin treatment, patients with proximal DVT were randomized to receive 2.5, 5.0, 7.5 or 10 mg of SanOrg34006 subcutaneously once weekly or warfarin (INR, 2.0-3.0) for 12 weeks. The primary efficacy outcome was the composite of change in thrombotic burden, as assessed by ultrasonography and perfusion lung scanning at baseline and week 12 +/- 1, and clinical thromboembolic events. This outcome was classified as normalization, no relevant change, or deterioration. Other outcomes were major and other clinically relevant bleeding. RESULTS: A total of 659 patients were randomized and treated. In 614 (93%) patients the primary efficacy outcome was evaluable. The rates of normalization and deterioration were similar in all SanOrg34006 groups (P = 0.4) and did not differ from the warfarin group. There was a clear dose-response for major bleeding among patients treated with SanOrg34006 (P = 0.003). Patients receiving 2.5 mg SanOrg34006 had less bleeding than did warfarin recipients (P = 0.03). CONCLUSIONS: SanOrg34006 dosed at 2.5 mg appears as effective as higher dosages and warfarin for secondary prevention in DVT and was not associated with major bleeding. Therefore, 2.5 mg of SanOrg34006 administered subcutaneously once weekly might be a suitable alternative to dose-adjusted oral vitamin K antagonist.
RCT Entities:
BACKGROUND:Vitamin K antagonists for secondary prevention in patients with deep vein thrombosis (DVT) require monitoring and dose adjustments. The synthetic factor Xa inhibitor, SanOrg34006, has predictable pharmacokinetics and may be administered once weekly without dose adjustments. METHODS: After 5-7 days of enoxaparin treatment, patients with proximal DVT were randomized to receive 2.5, 5.0, 7.5 or 10 mg of SanOrg34006 subcutaneously once weekly or warfarin (INR, 2.0-3.0) for 12 weeks. The primary efficacy outcome was the composite of change in thrombotic burden, as assessed by ultrasonography and perfusion lung scanning at baseline and week 12 +/- 1, and clinical thromboembolic events. This outcome was classified as normalization, no relevant change, or deterioration. Other outcomes were major and other clinically relevant bleeding. RESULTS: A total of 659 patients were randomized and treated. In 614 (93%) patients the primary efficacy outcome was evaluable. The rates of normalization and deterioration were similar in all SanOrg34006 groups (P = 0.4) and did not differ from the warfarin group. There was a clear dose-response for major bleeding among patients treated with SanOrg34006 (P = 0.003). Patients receiving 2.5 mg SanOrg34006 had less bleeding than did warfarin recipients (P = 0.03). CONCLUSIONS:SanOrg34006 dosed at 2.5 mg appears as effective as higher dosages and warfarin for secondary prevention in DVT and was not associated with major bleeding. Therefore, 2.5 mg of SanOrg34006 administered subcutaneously once weekly might be a suitable alternative to dose-adjusted oral vitamin K antagonist.