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.
OBJECTIVE
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.
Lassen
Michael R
MR
Hørsholm Hospital, Hørsholm, Denmark. mirula@noh.regionh.dk
Dahl
Ola
O
Mismetti
Patrick
P
Zielske
Dirk
D
Turpie
Alexander G G
AG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage*; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D017558:Elective Surgical Procedures / Q000009:adverse effects; D017984:Enoxaparin / Q000008:administration & dosage; D065427:Factor Xa Inhibitors; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009844:Oligosaccharides / Q000008:administration & dosage*; D010690:Phlebography; D011134:Polysaccharides / Q000008:administration & dosage*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D012307:Risk Factors; D054556:Venous Thromboembolism / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology
D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D009844:Oligosaccharides; D011134:Polysaccharides; C446839:SR 123781A; D011516:Prothrombin; C025337:Factor IIa