Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement

Peter Verhamme; Sophie Gunn; Elisabeth Sonesson; Kathelijne Peerlinck; Thomas Vanassche; Christophe Vandenbriele; Walter Ageno; Steven Glazer; Martin Prins; Harry Buller; Marco Tangelder

doi:10.1160/TH13-01-0066

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2013; 109(06): 1091-1098
DOI: 10.1160/TH13-01-0066

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement

A randomised, controlled trial

Authors

Peter Verhamme

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium

²Department of Vascular Medicine and Haemostasis, University Hospitals Leuven, Belgium
Sophie Gunn

³Clinical Department, ThromboGenics, Belgium
Elisabeth Sonesson

⁴Clinical Development, BioInvent International, Sweden
Kathelijne Peerlinck

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium

²Department of Vascular Medicine and Haemostasis, University Hospitals Leuven, Belgium
Thomas Vanassche

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium

²Department of Vascular Medicine and Haemostasis, University Hospitals Leuven, Belgium
Christophe Vandenbriele

¹Center for Molecular and Vascular Biology, University of Leuven, Belgium

²Department of Vascular Medicine and Haemostasis, University Hospitals Leuven, Belgium
Walter Ageno

⁵Department of Clinical Medicine, University of Insubria, Italy
Steven Glazer

⁴Clinical Development, BioInvent International, Sweden
Martin Prins

⁶Department of Epidemiology, University of Maastricht, The Netherlands
Harry Buller

⁷Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands
Marco Tangelder

³Clinical Department, ThromboGenics, Belgium

⁸Department of Vascular Surgery, University Medical Center Utrecht, The Netherlands

Abstract

Summary

TB-402 is a long-acting monoclonal antibody that partially inhibits factor VIII. A single administration of TB-402 was effective and well-tolerated for the prevention of venous thromboembolism (VTE) after total knee replacement. In this study, the efficacy and safety of a single administration of TB-402 for the extended prophylaxis of VTE after total hip replacement (THR) was investigated. This was a phase II, randomised, active-controlled, double-blind study that included patients undergoing elective THR surgery. Patients were randomised to TB-402 25 mg or TB-402 50 mg, administered as a single intravenous administration 2–4 hours postoperatively, or to rivaroxaban 10 mg once daily for 35 days. The primary efficacy outcome was total VTE defined as symptomatic VTE and asymptomatic deep-vein thrombosis (DVT) detected by bilateral venography at day 35. The principal safety outcome was the incidence of major bleeding and clinically relevant non-major bleeding until day 35. Total VTE was similar in all groups: 5.3% (95%CI 2.9–9.6), 5.2% (95%CI 2.8–9.3) and 4.7% (95%CI 2.5–8.7) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. All were asymptomatic DVTs. Major or clinically relevant non-major bleedings were observed in 5.8% (95%CI 3.3–9.9), 7.2% (95%CI 4.4–11.6) and 1.4% (95%CI 0.5–4.2) for TB-402 25 mg, TB-402 50 mg and rivaroxaban, respectively. In conclusion, TB-402, administered as a single postoperative dose, had a similar efficacy compared to rivaroxaban for the prevention of VTE after THR. The incidence of major and clinically relevant non-major bleeding was higher in the TB-402 groups than in the rivaroxaban group.

Keywords

Factor VIII - TB-402 - rivaroxaban - venous thromboembolism - thrombo-prophylaxis - deep-vein thrombosis - total hip replacement

Full Text

References

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