RECORD4

REgulation of Coagulation in major Orthopedic Surgery reducing the Risk of Deep Venous Thrombosis and Pulmonary Embolism 4 (2009)

Condition

Prophylaxis for VTE after total knee arthroplasty

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Objective

To compare the efficacy and safety of rivaroxaban with those of enoxaparin for the prevention of venous thromboembolism after elective total knee replacement

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Trial design

Randomized, double-blind phase III study
Active treatment: rivaroxaban 10 mg p.o. once daily (every 22–26 h), beginning 6–8 hours after wound closure and continued for 10–14 days; placebo injections as in control treatment (n=1584)
Control treatment: enoxaparin 30 mg s.c. every 10–14 hours, starting 12–24 hours after wound closure, administered for at least 10 days and up to day 14; placebo tablets as in active treatment (n=1564)

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Endpoints

Primary efficacy endpoint: composite of any DVT, non-fatal PE, and allcause mortality within 13–17 days after surgery
Secondary efficacy endpoints: major VTE (proximal DVT, non-fatal PE, or VTE-related death), DVT (any, proximal, distal), symptomatic VTE during treatment and follow-up, and death during the follow-up period Primary safety endpoint: major bleeding occurring between intake of the first dose of study drug and 2 days after the last dose
Secondary safety endpoints: any on-treatment bleeding, non-major bleeding, hemorrhagic wound complications, other adverse events, and death

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Trial participants

3148 patients ≥18 years scheduled for elective total knee replacement

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Results

Efficacy outcome: In the modified ITT population (n=1924), the primary efficacy endpoint (total VTE) occurred in 67 of 965 patients (6.9%) given rivaroxaban and in 97 of 959 patients (10.1%) given enoxaparin (absolute risk reduction 3.2%, relative risk reduction 31%). On-treatment in the rivaroxaban group there were 2 deaths and 4 patients had a pulmonary embolus; in the enoxaparin group, 3 patients died and pulmonary embolism occurred in 8 patients
Safety outcome: In the safety population (n=3034), major bleeding occurred in 10 of 1526 patients (0.7%) receiving rivaroxaban and in 4 of 1508 patients (0.3%) receiving enoxaparin. The incidences of drug-related adverse events were similar in the two groups: 20.3% with rivaroxaban and 19.6% with enoxaparin

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Summary

Efficacy: Oral rivaroxaban was significantly superior to subcutaneous enoxaparin for thromboprophylaxis after total knee arthroplasty
Safety: Although there were more major, major plus clinically relevant nonmajor, and any bleeding events with rivaroxaban, the differences compared with enoxaparin were not statistically significant

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Reference

Turpie AGG, Lassen MR, Davidson BL, Bauer KA, Gent M, Kwong LM, Cushner FD, Lotke PA, Berkowitz SD, Bandel TJ, Benson A, Misselwitz F, Fisher WD for the RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. The Lancet 2009;373:1673-1680

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Corresponding author

Alexander G. G. Turpie, MD, McMaster University, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada, e-mail: turpiea@mcmaster.ca

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