Dose-escalation study of rivaroxaban (BAY 59-7939)--an oral, direct Factor Xa inhibitor--for the prevention of venous thromboembolism in patients undergoing total hip replacement

Thromb Res. 2007;120(5):685-93. doi: 10.1016/j.thromres.2006.12.025. Epub 2007 Feb 12.


Introduction: Rivaroxaban (BAY 59-7939) is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention of thromboembolic disorders. The aim of this study was to demonstrate proof-of-principle for rivaroxaban.

Materials and methods: This was an open-label, dose-escalation study to assess the efficacy and safety of rivaroxaban, relative to enoxaparin, for the prevention of venous thromboembolism (VTE) after total hip replacement surgery. Patients were randomized in a 3:1 ratio to rivaroxaban (2.5, 5, 10, 20 and 30 mg twice daily [bid] or 30 mg once daily [od] starting 6-8 h after surgery) or enoxaparin (40 mg od starting the evening before surgery). Therapy continued until mandatory bilateral venography was performed 5-9 days after surgery.

Results: A total of 625 patients received therapy, of whom 466 patients were eligible for the per-protocol efficacy analysis. The primary efficacy endpoint - deep vein thrombosis (DVT), pulmonary embolism (PE) or all-cause mortality - occurred in 22.2%, 23.8%, 20.0%, 10.2%, 17.4%, 15.1% and 16.8% of patients receiving rivaroxaban 2.5, 5, 10, 20, 30 mg bid, 30 mg od and enoxaparin, respectively. The dose-response relationship with rivaroxaban for the primary efficacy endpoint was not statistically significant (p=0.0504), although major VTE (proximal DVT, PE and VTE-related death) decreased dose dependently with rivaroxaban (p=0.0108). Major, post-operative bleeding increased dose dependently with rivaroxaban (p=0.0008), occurring in 0-10.8% of patients, compared with 0% in patients receiving enoxaparin.

Conclusions: This study demonstrated proof-of-principle for rivaroxaban for the prevention of VTE after total hip replacement surgery.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Arthroplasty, Replacement, Hip / methods*
  • Factor Xa Inhibitors*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morpholines / therapeutic use*
  • Phlebography
  • Postoperative Complications / prevention & control
  • Rivaroxaban
  • Thiophenes / therapeutic use*
  • Treatment Outcome
  • Venous Thrombosis / complications*
  • Venous Thrombosis / prevention & control*


  • Factor Xa Inhibitors
  • Morpholines
  • Thiophenes
  • Rivaroxaban