Synthetic Oligosaccharide Prevents Clots After Hip Surgery

A new once-daily synthetic oligosaccharide is effective in preventing venous thromboembolism (VTE) after total hip replacement (THR), according to a new study.

Researchers from Horsholm Hospital (Denmark) attempted to examine if SR123781A, a synthetic oligosaccharide with a mixed profile of anti-factor Xa and IIa activities, could be an alternative to current treatments for VTE after THR. In a double-blind study, 1,023 patients participating in the DRIVE (Dose Ranging Study in Elective Total Hip Replacement Surgery) study were randomly assigned to one of five daily doses of SR123781A or to enoxaparin 40 mg. Treatment was continued for 10 days or until bilateral venography was performed, after a minimum of 5 days.

The study results showed that a significant dose-response effect for VTE was observed; VTE rates fell as the SR123781A dose increased, ranging from 21.2% with the lowest dose (0.25 mg) to 4.4% with the highest (4.0 mg). At the highest dose, the VTE rate was nearly half the rate seen with enoxaparin (8.7%). However, a high risk of bleeding was seen at this dose. The study was published in the April 15, 2008, issue of the Journal of the American College of Cardiology.

"Based on the data obtained in this dose-ranging study, the resulting model suggests that SR123781A doses ranging from 1.5 to 2.5 mg show a reasonable risk-to-benefit ratio for the prevention of VTE in patients undergoing major orthopedic surgery,” concluded lead author Michael Lassen, M.D., and colleagues of the department of clinical research.

SR123781A, developed by Sanofi-Synthélabo (Toulouse, France), is a synthetic hexadecasaccharide comprising an antithrombin (AT) binding domain, a thrombin-binding domain, and a neutral methylated hexasaccharide sequence, and is obtained from glucose through a convergent synthesis. In addition, unlike heparin, it does not interact with platelet factor 4 (PF4) and does not activate human platelets in the presence of plasma from heparin-induced thrombocytopenia patients. Several preclinical reports have demonstrated that it exhibits prolonged anti-Xa and antithrombin activities, a high subcutaneous bioavailability, and potent venous and arterial antithrombotic effects in rats and pigs.


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Horsholm Hospital
Sanofi-Synthélabo