title: Single-dose TB-402 or rivaroxaban for the prevention of venous thromboembolism after total hip replacement. A randomised, controlled trial.
abstract: 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.
authors.affiliation: Center for Molecular and Vascular Biology, KU Leuven, Herestraat 49 / box 911, B-3000 Leuven, Belgium. Peter.Verhamme@med.kuleuven.be
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.forename: Sophie
authors.initials: S
authors.lastname: Gunn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sonesson
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peerlinck
authors.forename: Thomas
authors.initials: T
authors.lastname: Vanassche
authors.forename: Christophe
authors.initials: C
authors.lastname: Vandenbriele
authors.forename: Walter
authors.initials: W
authors.lastname: Ageno
authors.forename: Steven
authors.initials: S
authors.lastname: Glazer
authors.forename: Martin
authors.initials: M
authors.lastname: Prins
authors.forename: Harry
authors.initials: H
authors.lastname: Buller
authors.forename: Marco
authors.initials: M
authors.lastname: Tangelder
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D061214:Patient Safety; D011183:Postoperative Complications / Q000517:prevention & control; D012306:Risk; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000150:complications / Q000517:prevention & control*; D020246:Venous Thrombosis / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000925:Anticoagulants; D009025:Morpholines; C559990:TB 402; D013876:Thiophenes; D000069552:Rivaroxaban