A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement

N Engl J Med. 2001 Mar 1;344(9):619-25. doi: 10.1056/NEJM200103013440901.


Background: Venous thromboembolism is a frequent complication of total hip replacement. The pentasaccharide Org31540/SR90107A, a highly selective, indirect inhibitor of activated factor X, is the first of a new class of synthetic antithrombotic agents. To determine the optimal dose for phase 3 studies, we conducted a dose-ranging study in which Org31540/SR90107A was compared with a low-molecular-weight heparin, enoxaparin, in patients undergoing total hip replacement.

Methods: In a double-blind study, patients were randomly assigned to postoperative administration of one of five daily doses of Org31540/SR90107A, given once daily, or to 30 mg of enoxaparin, given every 12 hours. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.

Results: Of 933 patients treated, 593 were eligible for the efficacy analysis. With Org31540/SR90107A a dose effect was observed (P=0.002), with rates of venous thromboembolism of 11.8 percent, 6.7 percent, 1.7 percent, 4.4 percent, and 0 percent for the groups assigned to 0.75 mg, 1.5 mg, 3.0 mg, 6.0 mg, and 8.0 mg of the drug, respectively, as compared with a rate of 9.4 percent in the enoxaparin group. The reduction in the risk of venous thromboembolism was 82 percent for the 3.0-mg Org31540/SR90107A group (P=0.01) and 29 percent for the 1.5-mg group (P=0.51). Enrollment in the 6.0-mg and 8.0-mg Org31540/SR90107A groups was discontinued because of bleeding complications. Major bleeding occurred 3.5 percent less frequently in the 0.75-mg group (P=0.01) and 3.0 percent less frequently in the 1.5-mg group (P=0.05) than in the enoxaparin group (in which the rate was similar to that in the 3.0-mg group).

Conclusions: A synthetic pentasaccharide, Org31540/SR90107A, has the potential to improve significantly the risk-benefit ratio for the prevention of venous thromboembolism, as compared with low-molecular-weight heparin.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Anticoagulants / pharmacology
  • Arthroplasty, Replacement, Hip*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Enoxaparin / adverse effects
  • Enoxaparin / therapeutic use
  • Female
  • Fibrinolytic Agents / administration & dosage
  • Fibrinolytic Agents / adverse effects
  • Hemorrhage / chemically induced
  • Humans
  • Injections, Subcutaneous
  • Logistic Models
  • Male
  • Middle Aged
  • Oligosaccharides / administration & dosage*
  • Oligosaccharides / adverse effects
  • Oligosaccharides / pharmacology
  • Postoperative Complications / prevention & control*
  • Pulmonary Embolism / prevention & control
  • Thromboembolism / prevention & control
  • Venous Thrombosis / prevention & control*


  • Anticoagulants
  • Enoxaparin
  • Fibrinolytic Agents
  • Oligosaccharides