Premium
A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgery
Author(s) -
ERIKSSON B. I.,
TURPIE A. G. G.,
LASSEN M. R.,
PRINS M. H.,
AGNELLI G.,
KÄLEBO P.,
GAILLARD M. L.,
MEEMS L
Publication year - 2007
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2007.02644.x
Subject(s) - medicine , venography , incidence (geometry) , clinical endpoint , venous thromboembolism , surgery , adverse effect , cohort , risk factor , anesthesia , randomized controlled trial , thrombosis , physics , optics
Summary. Background : YM150, a new oral direct factor Xa inhibitor is used as prophylaxis for venous thromboembolism (VTE), a well‐known risk after orthopaedic surgery. Objectives : To assess the safety and efficacy of thromboprophylaxis with YM150 in a dose escalation study. Patients/methods : Patients (174) undergoing hip replacement surgery were randomized per cohort to oral once daily YM150 or subcutaneous enoxaparin (40 mg daily) in a 4:1 ratio for 7–10 days treatment. The YM150 doses were 3, 10, 30 and 60 mg by sequential four‐dose escalation cohorts. The primary endpoint was major and/or clinically relevant non‐major bleeding. The incidence of VTE was defined as a composite of verified symptomatic events and/or positive findings at bilateral venography on the last treatment day. An independent adjudication committee evaluated blindly the outcomes of the open‐label study. Results : No major and three clinically relevant non‐major bleeds were reported, 1 (2.9%; 95% CI, 0.1–15.1) in the 3 mg and 2 (5.7%; 95% CI, 1.0–18.8) in the 10 mg YM150 dose groups. Of 147 patients (84%) with an evaluable venogram, VTE was observed in 51.9% (95% CI, 31.9–71.4), 38.7% (95% CI, 22.6–57.0), 22.6% (95% CI, 9.7–39.4), and 18.5% (95% CI, 7.5–36.5) in the YM150 dose groups 3, 10, 30 and 60 mg, respectively. A significant YM150 dose‐related trend in VTE incidence was found ( P =0.006). VTE with enoxaparin was 38.7% (95% CI, 22.6–57.0). Conclusions : YM150, 10–60 mg daily, starting 6–10 h after primary hip replacement, was shown to be safe, well tolerated and effective.