title: Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3).
abstract: This double-blind, double-dummy, randomised, phase IIb study (NCT00902928) evaluated different dosing regimens of darexaban compared with enoxaparin (randomised 1:1:1:1:1 to 15 mg twice daily [bid], 30 mg once daily [qd], 30 mg bid or 60 mg qd or enoxaparin 40 mg qd) in patients undergoing elective total hip arthroplasty. Patients, investigators, pharmacists and sponsor were all blinded to treatment allocation. Darexaban administration started 6-10 hours (h) post-surgery. Enoxaparin 40 mg qd administration started 12 ± 2 h before surgery. Treatment continued for 35 days. Bilateral venography was performed on Day 10 ± 2. The primary efficacy outcome was total VTEs (composite of proximal/distal deep-vein thrombosis, pulmonary embolism) or death, at Day 12. Total VTE rates were similar across all groups. There was no apparent difference in efficacy between once- and twice-daily darexaban (odds ratio [OR] 1.00; 95% confidence interval [CI] 0.71-1.42; p=0.988), or total daily dose (30 mg/day vs 60 mg/day; OR 0.81; 95% CI 0.57-1.15; p=0.244). There was no significant difference in major and/or clinically relevant non-major bleeding between darexaban qd or bid, or between total daily doses of 30 mg or 60 mg, and also for any dosing regimen of darexaban vs enoxaparin. Darexaban was well tolerated, without signs of liver toxicity. In conclusion, darexaban, administered qd or bid, and at total daily doses of 30 mg or 60 mg, appears to be effective for VTE prevention and was well tolerated. Data suggest no significant differences between a once- or twice-daily dosing regimen.
authors.affiliation: Bengt I. Eriksson, MD, PhD, Sahlgrenska University Hospital, Gothenburg, Sweden, Tel: +46 31 343 4408, Fax: +46 3 187 8531, E-mail: bengt.eriksson@gu.se.
authors.forename: Bengt I
authors.initials: BI
authors.lastname: Eriksson
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Gallus
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lassen
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Ronny W
authors.initials: RW
authors.lastname: Renfurm
authors.forename: Makoto
authors.initials: M
authors.lastname: Kashiwa
authors.forename: Alexander G G
authors.initials: AG
authors.lastname: Turpie
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D001315:Australia; D001381:Azepines / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage* / Q000009:adverse effects; D001938:Brazil; D002170:Canada; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017558:Elective Surgical Procedures; D017984:Enoxaparin / Q000008:administration & dosage* / Q000009:adverse effects; D005060:Europe; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D007194:India; D007557:Israel; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010690:Phlebography; D012307:Risk Factors; D013019:South Africa; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States; D054556:Venous Thromboembolism / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D001381:Azepines; D001549:Benzamides; D017984:Enoxaparin; C569750:darexaban
keywords: Darexaban; bleeding; enoxaparin; orthopaedic surgery; venous thromboembolism