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EXPEDITED PUBLICATION: ACC RAPID TRACK ABSTRACT

SR123781A: A New Once-Daily Synthetic Oligosaccharide Anticoagulant for Thromboprophylaxis After Total Hip Replacement Surgery

The DRIVE (Dose Ranging Study in Elective Total Hip Replacement Surgery) Study

Michael R. Lassen, MD^_*,_*, Ola Dahl, MD, PhD, Patrick Mismetti, MD, Dirk Zielske, MD and Alexander G.G. Turpie, MD, FACC^||

^_* Hørsholm Hospital, Hørsholm, Denmark
Thrombosis Research Institute, London, England
University Hospital of Saint-Étienne, Saint-Étienne, France
sanofi-aventis, Frankfurt am Main, Germany
^|| McMaster University, Hamilton, Ontario, Canada.

Manuscript received January 18, 2008; revised manuscript received March 5, 2008, accepted March 10, 2008.

^_* Reprint requests and correspondence: Dr. Michael R. Lassen, Hørsholm Hospital, Spine Clinic, Clinical Trial Unit Usserød Kongevej 102, DK-2970 Hørsholm, Denmark. (Email: mirula{at}noh.regionh.dk).

Objectives: This study assessed the dose response of SR123781A for the prevention of venous thromboembolism (VTE) in patients undergoing total hip replacement (THR) surgery.

Background: Despite VTE preventive measures, residual VTE complications still occur after THR. SR123781A, a synthetic oligosaccharide with a mixed profile of anti-factor Xa and IIa activities, could be an alternative to current treatments.

Methods: In this double-blind study, 1,023 patients undergoing THR were randomly assigned to 1 of 5 daily doses of SR123781A or to a calibrator arm of enoxaparin 40 mg. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.

Results: A significant dose-response effect for VTE was observed for SR123781A (p < 0.0001). The VTE rates were 21.2%, 17.7%, 13.5%, 7.0%, and 4.4% in the 0.25-, 0.5-, 1.0-, 2.0-, and 4.0-mg dose groups of SR123781A, respectively, and 8.7% in the enoxaparin group. Doses of 2.0 and 4.0 mg of SR123781A reduced the risk of VTE by 67% and 79%, respectively, compared with the 0.25-mg dose group. Major bleeding was observed in 1.2%, 0.6%, 0.6%, 0.6%, and 5.8% of the patients in the 0.25-, 0.5-, 1.0-, 2.0-, and 4.0-mg dose groups of SR123781A, respectively, and in 0.6% of patients in the enoxaparin group. The dose-response effect for major bleeding was significant (p = 0.0037).

Conclusions: The model based on these dose-finding study results suggests that SR123781A doses ranging from 1.5 to 2.5 mg show a reasonable risk-to-benefit ratio for VTE prevention after major orthopedic surgery. (Dose Ranging Study in Elective Total Hip Replacement Surgery [DRIVE]; NCT00338897 [ClinicalTrials.gov] )

Abbreviations and Acronyms   CI = confidence interval   DVT = deep vein thrombosis   PE = pulmonary embolism   THR = total hip replacement   VTE = venous thromboembolism