Treatment of proximal deep vein thrombosis with a novel synthetic compound(SR90107A/ORG31540) with pure anti-factor Xa activity - A phase II evaluation

Background-Patients with venous thromboembolism require initial treatment w ith an immediate-acting anticoagulant, low-molecular-weight heparin. We eva luated a novel synthetic factor Xa inhibitor (SR90107a/ORG31540) as an alte rnative treatment. Methods and Results-A randomized-parallel-group, phase II trial to assess t he efficacy and safety of SR90107a/ORG31540 (5, 7.5, or 10 mg once daily) r elative to low-molecular-weight heparin (dalteparin, 100 IU/kg twice daily) in symptomatic proximal deep vein thrombosis. The primary outcome measure was the change in thrombus mass, assessed by ultrasonography of the leg vei ns and perfusion lung scintigraphy, performed at baseline and day 7+/-1. A positive outcome was defined as improvement of the ultrasound and/or perfus ion scan result without deterioration of either test. Other outcome measure s included symptomatic, recurrent venous thromboembolism and major bleeding for a period of 3 months. All outcomes were interpreted with the observer unaware of treatment allocation. A positive primary outcome was observed in 46 of 100 (46%), 52 of 108 (48%), 48 of 115 (42%), and 56 of 115 (49%), re spectively, of the subjects given 5, 7.5, or 10 mg SR90107a/ORG31540 or dal teparin. There were 8 recurrent thromboembolic complications (2.4%) in the 334 patients treated with SR90107a/ORG31540 and 6 (5.0%) in the 119 daltepa rin patients, a difference of 2.6% in favor of SR90107a/ORG31540 (95% CI -2 .1% to 10.1%). The incidence of bleeding was low and was similar among the groups. Conclusions-The factor Xa inhibitor SR90107a/ORG31540 appears to be an effe ctive and safe treatment for patients with deep vein thrombosis across a wi de range of doses. This synthetic compound merits evaluation in phase III s tudies.