Comparison of XXXX , an oral direct @entity556 inhibitor, with @entity2120 for the prevention of @entity1211 following total hip replacement. A randomized, double-blind study.

@entity1 @entity556 @entity548 @entity1151 @entity1150 @entity715 @entity1211 @entity2120 @entity24772
BACKGROUND: Prophylaxis is recommended following total joint replacement because of the high risk of @entity1211 ( @entity1211 ). Postoperative low-molecular-weight heparin (LMWH) reduces the incidence of venographically detected @entity1150 ( @entity1150 ) to about 10-15% in total hip replacement (THR) @entity1 . @entity24772 is a novel, oral direct @entity556 inhibitor that selectively and competitively inhibits both free and clot-bound @entity556 . We compared the efficacy and safety of @entity24772 with those of @entity2120 for the prevention of @entity1211 in @entity1 undergoing THR. METHODS: This was a prospective, randomized, multicenter, double-blind study conducted principally in the USA and Canada. @entity1 received fixed-dose oral @entity24772 24 mg bid or subcutaneous @entity2120 30 mg bid and matched placebo for 7-12 days; both regimens were initiated the morning after surgery. The incidence of @entity1211 (by postoperative day 12) included @entity715 determined by mandatory venography of the leg on which surgery was performed and symptomatic, objectively proven @entity1150 or @entity1151 ( @entity1151 ). @entity1211 and @entity548 events were interpreted by an independent central adjudication committee for primary analysis. RESULTS: Of the 1838 @entity1 randomized, 1557 had either adequate venography or symptomatic, proven @entity1211 (efficacy population). Overall rate of venography acceptable for evaluation was 85.4%. Overall rates of total @entity1211 were 7.9% (62 of 782 @entity1 ) in the @entity24772 group and 4.6% (36 of 775 @entity1 ) in the @entity2120 group, with an absolute difference of 3.3% and a 95% confidence interval for the difference of 0.9% to 5.7%. Proximal @entity1150 and/or @entity1151 occurred in 3.6% (28 of 782 @entity1 ) in the @entity24772 group and 1.2% (nine of 774 @entity1 ) in the @entity2120 group. Major @entity548 events were observed in 0.8% (seven of 906) of the @entity24772 -treated @entity1 and in 0.9% (eight of 910) of the @entity2120 -treated @entity1 (P > 0.95). Non-inferiority of @entity24772 24 mg bid based on a prespecified margin of 5% was not met, resulting in superiority of the @entity2120 regimen. CONCLUSIONS: Both @entity24772 and @entity2120 decreased the overall rate of @entity1211 compared with that reported historically. However, in this study, @entity2120 30 mg bid was more effective than @entity24772 24 mg bid for prevention of @entity1211 in THR. Oral @entity24772 was used without coagulation monitoring, was well tolerated, and had @entity548 rates comparable to those of @entity2120 . Further refinement by testing a higher dose of @entity24772 in the @entity1 undergoing THR is warranted.
