A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgery.

Abstract

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.

• Authors: B I Eriksson, A G G Turpie, M R Lassen, M H Prins, G Agnelli, P Kälebo, M L Gaillard, L Meems, ONYX study group
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 5 Issue 8 Pg. 1660-5 (Aug 2007) ISSN: 1538-7933 [Print] England
• PMID: 17663737 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Enoxaparin
• Antithrombin III

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antithrombin III (administration & dosage, pharmacology)
• Arthroplasty, Replacement, Hip (methods)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Enoxaparin (therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Treatment Outcome
• Venous Thrombosis (prevention & control)