RE-MODEL

Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement (2007)

Condition

Prophylaxis for VTE after total knee replacement

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Objective

To prove non-inferiority of dabigatran compared to enoxaparin in the prevention of venous thromboembolism after total knee replacement

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Trial design

Randomized, double-blind phase III study
Active treatment: dabigatran 150 mg (n=703) or 220 mg (n=679) p.o. once daily, starting 1–4 hours after surgery with half dose on the first day, for 6–10 days; placebo injections as in control treatment
Control treatment: enoxaparin 40 mg s.c. once daily, starting in the evening before surgery for 6–10 days; placebo tablets as in active treatment (n=694)

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Endpoints

Primary efficacy endpoint: composite of total VTE and death from any cause during treatment
Secondary efficacy endpoints: composite of major VTE (proximal DVT and PE) and VTE-related mortality, proximal DVT, the incidence of total VTE and all-cause mortality during follow-up
Primary safety endpoint: major bleeding
Secondary safety endpoints: bleeding events during study treatment; hepatic enzyme abnormalities and suspected cardiovascular events during study treatment and follow-up

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Trial participants

2101 patients (mean age 68 years), scheduled for elective total knee replacement

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Results

Efficacy outcome: In patients with evaluable efficacy outcome (n=1541), the primary efficacy endpoint (all DVT, symptomatic PE and death from any cause) occurred in 213 of 526 patients (40.5%) given 150 mg dabigatran, in 183 of 503 patients (36.4%) given 220 mg dabigatran and in 193 of 512 patients (37.7%) given enoxaparin. Both doses of dabigatran were non-inferior to enoxaparin (p=0.017 for 150 mg, p=0.0003 for 220 mg). The secondary outcome of major VTE and VTE-related mortality occurred in 2.6% and 3.8% of the dabigatran 220-mg and 150-mg groups, as compared with 3.5% of the enoxaparin group
Safety outcome: In the study population of 2076 patients major bleeding occurred in 9 of 703 patients (1.3%) receiving 150 mg dabigatran, in 10 of 679 patients (1.5%) receiving 220 mg dabigatran and in 9 of 694 patients (1.3%) receiving enoxaparin. None of the major bleeding events was fatal. Clinically relevant non-major bleeding developed in 6.8%, 5.9%, and 5.3% of the patients receiving 150 mg dabigatran, 220 mg dabigatran, and enoxaparin, respectively. The incidences for minor bleeding were 8.4%, 8.8%, and 9.9%

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Summary

Efficacy: Oral administration of dabigatran was non-inferior to subcutaneous enoxaparin for the combined endpoint of DVT, symptomatic PE and death
Safety: The rate of minor and major bleeding was comparable in all 3 study groups

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Reference

Eriksson BI, Dahl OE, Rosencher N, Kurth AA, van Dijk CN, Frostick SP, Kälebo P, Christiansen AV, Hantel S, Hettiarachchi R, Schnee J, Büller HR; RE-MODEL Study Group. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007;5:2178-2185

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Corresponding author

B.I. Eriksson, Orthopaedics Department, Sahlgrenska University Hospital/Östra, SE-41685 Göteborg, Sweden, e-mail: b.eriksson@orthop.gu.se

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