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Thromb Haemost 2014; 111(02): 213-225
DOI: 10.1160/TH13-04-0296
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Darexaban (YM150) versus enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a randomised phase IIb dose confirmation study (ONYX-3)

Bengt I. Eriksson
1   Sahlgrenska University Hospital, Gothenburg, Sweden
,
Giancarlo Agnelli
2   University of Perugia, Perugia, Italy
,
Alexander S. Gallus
3   Flinders Medical Centre, Adelaide, Australia
,
Michael R. Lassen
4   Spine Center Copenhagen, Copenhagen University Hospital, Glostrup, Denmark
,
Martin H. Prins
5   University of Maastricht, Maastricht, The Netherlands
,
Ronny W. Renfurm
6   Astellas Pharma Global Development Europe, Leiden, The Netherlands
7   Department of Cardiology C5-P, Leiden University Medical Center, Leiden, The Netherlands
,
Makoto Kashiwa
8   Astellas Pharma Inc, Tokyo, Japan
,
Alexander G. G. Turpie
9   Hamilton General Hospital, Hamilton, Canada
› Author Affiliations Financial support: This study was funded by Astellas. Editorial support for the preparation of this manuscript was funded by Astellas.
Further Information

Publication History

Received: 10 April 2013

Accepted after major revision: 13 February 2013

Publication Date:
27 November 2017 (online)

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Summary

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 onceand 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.

Keywords

Darexaban - enoxaparin - orthopaedic surgery - venous thromboembolism - bleeding

 

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