PENTATHLON

PENTAsaccharide in Total Hip replacement, or LOw-molecular-weight hepariN (2002)

Condition

Prophylaxis for VTE after elective hip-replacement surgery

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Objective

To compare the efficacy and safety of fondaparinux and enoxaparin for VTE prophylaxis after elective total hip replacement

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Trial design

Randomized, double-blind study with parallel groups
Active treatment: fondaparinux 2.5 mg s.c. once daily, initiated 4–8 hours postoperatively, for 5–9 days; enoxaparin placebo (n=1138)
Control treatment: enoxaparin 30 mg s.c. twice daily, first dose given
12–24 hours after surgery, for 5–9 days; fondaparinux placebo (n=1137)

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Endpoints

Primary efficacy endpoint: DVT and PE up to day 11 after surgery
Secondary efficacy endpoints: total, proximal, or distal DVT or symptomatic VTE up to day 11 and symptomatic VTE up to day 49
Primary safety endpoint: major bleeding
Secondary safety endpoints: minor bleeding, death, blood transfusion requirement, thrombocytopenia

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Trial participants

2275 patients (mean age 67 years) undergoing a first elective total hip replacement or a revision of at least one component of a previously implanted total hip prosthesis

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Results

Efficacy outcome: 1584 patients were included in the primary efficacy analysis. The primary efficacy outcome of VTE up to day 11 occurred in 48 of 787 patients (6.1%) receiving fondaparinux and in 66 of 797 patients (8.3%) receiving enoxaparin (relative risk reduction 26%, but the difference was not significant; p=0.099). The incidence of proximal DVT was nearly the same in both groups, 1.7% with fondaparinux and 1.2 with enoxaparin. Distal DVT developed in 4.3% of patients assigned to fondaparinux and 6.8% of patients treated with enoxaparin (relative risk reduction 37%, p=0.037). Non-fatal and fatal PE was recorded in 5 patients receiving fondaparinux (0.4%) and 1 patient given enoxaparin (0.1%). By day 49, more patients on fondaparinux had symptomatic VTE than those on enoxaparin (2.6% vs. 1.2%; p=0.013)
Safety outcome: At day 11, the primary safety outcome of major bleeding had occurred in 20 of 1128 (1.8%) fondaparinux-treated patients and in 11 of 1129 (1.0%) patients in the enoxaparin group. The rates for minor bleeding, transfusion requirements and other adverse events did not differ significantly between groups. At the end of follow-up, 6 patients given fondaparinux (0.5%) and 3 patients given enoxaparin (0.3%) had died

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Summary

Efficacy: Fondaparinux was not significantly more effective than enoxaparin in reducing risk of VTE after elective total hip replacement. However, the 26% reduction in risk recorded for fondaparinux was clinically important
Safety: The two groups did not differ in the incidence of clinically relevant bleeding and all-cause death

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Reference

Turpie AGG, Bauer KA, Eriksson BI, Lassen MR, for the PENTATHLON 2000 Study Steering Committee. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet 2002;359:1721-1726

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Corresponding author

Prof. Alexander G.G. Turpie, Hamilton Health Sciences, General Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada, e-mail: turpiea@mcmaster.ca

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