Once Weekly Subcutaneous Idraparinux Versus Placebo in the Extended Treatment of Deep-Vein Thrombosis or Pulmonary Embolism. The van Gogh Investigators.

Background. Although vitamin K antagonists are effective for treatment of venous thrombo-embolism, in many patients their extended use is constrained by limitations of risk-benefit and inconvenience. We evaluated whether an extended six-month treatment with idraparinux would be effective and safe in patients with venous thrombo-embolism who had received an initial 6-month anticoagulant treatment.

Methods. We randomly assigned patients warranting consideration of extending anticoagulation, and who had completed 6-months of either idraparinux or vitamin K antagonist treatment, to once weekly injections of either 2.5 mg of idraparinux without monitoring or placebo for 6 months. Recurrent venous thrombo-embolism and major bleeding were assessed during this period as the primary efficacy and safety outcomes.

Results. Of 1215 patients, 6 (1.0 percent) idraparinux and 23 (3.7 percent) placebo recipients had recurrent venous thrombo-embolism (p=0.002). Eleven (1.9 percent) idraparinux, but no placebo recipients, had major bleeding (p=0.0007), including 3 fatal intracranial bleeds. The patients previously treated with idraparinux (versus a vitamin K antagonist) had a lower incidence of recurrent thrombo-embolism among those randomized to placebo (0.7 versus 5.9 percent, respectively P=0.003), and a higher incidence of major bleeding among those randomized to idraparinux. (3.1 versus 0.9 percent, respectively, P=0.1647).

Conclusion: This placebo controlled trial demonstrated the effectiveness of idraparinux during a 6-month extended treatment, at the expense of an increased risk of bleeding. Previous administration of idraparinux was associated with extended anti thrombotic activity in the placebo recipients.