PENTAMAKS

PENTAsaccharide in MAjor Knee Surgery study (2001)

Condition

Prophylaxis for VTE after elective major knee surgery

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Objective

To compare the efficacy and safety of fondaparinux and enoxaparin for VTE prophylaxis after elective major knee surg

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Trial design

Randomized, double-blind, study with parallel groups
Active treatment: fondaparinux 2.5 mg s.c. once daily, initiated 6±2 hours postoperatively, second dose given ≥12 hours after the first, treatment for 5–9 days; enoxaparin placebo (n=517)
Control treatment: enoxaparin 30 mg s.c. twice daily, first dose given
12–24 hours after surgery, for 5–9 days; fondaparinux placebo (n=517)

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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

1049 patients (mean age 67.5 years) scheduled to undergo major knee surgery (resection of the distal end of the femur or proximal end of the tibia or revision of at least one component of a previously implanted total-knee prosthesis)

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Results

Efficacy outcome: 724 patients were included in the primary efficacy analysis. At day 11, the incidence of VTE was 12.5% in the fondaparinux group (101 of 363 patients) and 27.8% in the enoxaparin group (45 of 361 patients). The resulting relative risk reduction was 55% (p<0.001). Proximal DVT occurred in 2.4% of patients assigned to fondaparinux and 5.4% of patients treated with enoxaparin (relative risk reduction 55%, p<0.001). Non-fatal PE developed in 1 patient receiving fondaparinux (0.2%) and 4 patients given enoxaparin (0.8%). By day 49, the incidence of symptomatic VTE did not differ significantly between both groups (1.0% in the fondaparinux group vs. 1.9% in the enoxaparin group
Safety outcome: At day 11, the primary safety outcome of major bleeding had occurred significantly more frequently in the fondaparinux-treated patients: 2.1% (11 of 517 patients) vs. 0.2% (1 of 517 patients) in the enoxaparin group. But there were no significant differences in the incidence of bleeding leading to death or reoperation or occurring in a critical organ. The rates for minor bleeding, transfusion requirements and other adverse events did not differ significantly between groups. At the end of follow-up, 2 patients treated with fondaparinux (0.4%) and 3 treated with enoxaparin (0.6%) had died

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Summary

Efficacy: Fondaparinux was superior to enoxaparin in preventing VTE after elective major knee surgery
Safety: Major bleeding was significantly more frequent in patients treated with fondaparinux, but there were no significant differences between both groups in the incidence of fatal bleeding, bleeding in critical organs or bleeding leading to reoperation

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Reference

Bauer KA, Eriksson BI, Lassen MR, Turpie AGG, for the Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med 2001;345:1305-1310

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Corresponding author

Kenneth A. Bauer, MD, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, e-mail: kbauer@caregroup.harvard.edu

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