AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study.

Abstract

BACKGROUND:

AVE5026 is a new hemisynthetic ultra-low-molecular-weight heparin, with a novel anti-thrombotic profile resulting from high anti-factor (F)Xa activity and residual anti-FIIa activity. AVE5026 is in clinical development for venous thromboembolism (VTE) prevention, a frequent complication after total knee replacement (TKR) surgery.

OBJECTIVES:

This study evaluated the dose-response of AVE5026 for the prevention of VTE in patients undergoing TKR surgery.

PATIENTS/METHODS:

In this parallel-group, double-blind, double-dummy study, 690 patients were randomized, and 678 treated with once-daily doses of AVE5026 (5, 10, 20, 40, or 60 mg) or enoxaparin 40 mg in the calibrator arm. The primary efficacy end point was VTE until post-operative day 11, defined as deep vein thrombosis (DVT) detected by bilateral venography, symptomatic DVT, non-fatal pulmonary embolism (PE) and VTE-related death. The primary safety outcome was the incidence of major bleeding.

RESULTS:

The primary efficacy outcome was assessed in 464 patients. There was a significant dose-response across the five AVE5026 groups for VTE prevention (P<0.0001), with the incidence of VTE ranging from 5.3% to 44.1% compared with 35.8% in the enoxaparin group and for proximal DVT (P=0.0002). Also, a significant dose-response for AVE5026 was seen for major bleeding (P=0.0231) and any bleeding (P=0.0003). Six patients in the AVE5026 groups, four in the 60 mg group, experienced major bleeding; none did in the enoxaparin group.

CONCLUSIONS:

The safety and efficacy results of this study suggest that a AVE5026 dose of between 20 and 40 mg presents an adequate benefit-to-risk ratio.

• Authors: M R Lassen, O E Dahl, P Mismetti, D Destrée, A G G Turpie
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 7 Issue 4 Pg. 566-72 (Apr 2009) ISSN: 1538-7836 [Electronic] England
• PMID: 19187076 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• AVE 5026
• Heparin, Low-Molecular-Weight
• Heparin

Topics

• Adult
• Aged
• Aged, 80 and over
• Arthroplasty, Replacement, Knee (adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Hemorrhage (chemically induced)
• Heparin (administration & dosage, analogs & derivatives)
• Heparin, Low-Molecular-Weight (administration & dosage, toxicity)
• Humans
• Male
• Middle Aged
• Postoperative Complications (prevention & control)
• Premedication (methods)
• Risk Assessment
• Venous Thromboembolism (prevention & control)