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Pentasaccharide for the Prevention of Deep-Vein Thrombosis after Total Hip Replacement - Pentasaccharide for the Prevention of Deep-Vein Thrombosis after Total Hip Replacement
Description:
A Synthetic Pentasaccharide for the Prevention of Deep-Vein Thrombosis after Total Hip Replacement.
Hypothesis:
What is the optimal effective and safe dose of the pentasaccharide Org31540/SR90107A (ORG), a synthetic, highly selective indirect inhibitor of activated factor X as compared to low-molecular heparin (enoxiparin) for the prevention of deep-vein thrombosis in patients undergoing total hip replacement?
Study Design
Study Design:
Patients Enrolled: 933
Drug/Procedures Used:
Patients were randomly assigned in a double-blind fashion to receive one of five daily doses of ORG, given once daily, or to 30mg of enoxaparin, given every 12 hours (first dose 12 hours after surgery) 6 hours following hip replacement<>. Treatment was continued for 10 days or until bilateral venography was performed after a minimum of 5 days.
Principal Findings:
A total of 593 of 933 patients treated were eligible for the efficacy analysis. ORG use was associated with decreasing rates of venous thromboembolism with higher doses (11.8%, 6.7%, 1.7%, 4.4% and 0% for the groups assigned to 0.75mg, 1.5mg, 3.0mg, 6.0mg and 8.0mg of the drug, respectively, p = 0.0002). The rate of venous thromboembolism was 9.4% in the enoxaparin group. Thus, the risk reduction of venous thromboembolism was 82% for the 3.0-mg ORG group (p = 0.01) and 29% for the 1.5-mg group (p = 0.51) vs. enoxaparin. Enrollment in the two highest ORG groups (6mg and 8mg) was discontinued because of increased bleeding complications. The proportion of patients with major bleeding was significantly higher in the enoxaparin group than in the 0.75-mg group (by 3.5%, p = 0.01) and the 1.5-mg group (by 3.0%, p = 0.05) and was similar to that in the 3.0-mg group).
In patients undergoing hip surgery, ORG has the potential to improve the prevention of venous thromboembolism as compared with low–molecular-weight heparin.
Interpretation:
Selective inhibition of factor Xa achieved by this synthetic pentasaccharide has the potential for strong inhibition of thrombin generation and growth. In addition, unlike heparin, this agent does not interact with platelets or platelet factor 4, eliminating the need to monitor platelet levels. ORG’s linear pharmacokinetics and longer half-life to promote reproducible and predictable results with single daily dose. This study establishes the dose-response curves for safety and efficacy and helps identify the optimal dose of ORG for future large randomized clinical trials.
References:
Turpie AG, Gallus AS, Hoek JA, for the Pentasaccharide Investigators. N Engl J Med 2001;344:619-25.
Clinical Topics: Anticoagulation Management, Dyslipidemia, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Lipid Metabolism, Novel Agents, Angiography, Nuclear Imaging
Keywords: Arthroplasty, Replacement, Hip, Thrombin, Risk Reduction Behavior, Enoxaparin, Phlebography, Heparin, Low-Molecular-Weight, Pulmonary Embolism, Venous Thromboembolism, Platelet Factor 4, Blood Platelets, Factor Xa
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