A PHASE II DOUBLE-BLIND PLACEBO-CONTROLLED PARALLEL-GROUP RANDOMIZED STUDY OF EXTENDED PROPHYLAXIS WITH ODIPARCIL FOLLOWING TOTAL HIP ARTHROPLASTY (THA)
Abstract number: P-M-653
Bates1 S.M., Buller2 H., Lassen3 M.R., Samama4 M.M., Whitsett5 T., Fischer6 L., Danoff7 T.M., Froloshki8 B.S., Asbel8 N.R., Ginsberg1 J.S.
11Medicine, McMaster University, Hamilton, Canada 22Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands 33Orthopaedics, University of Copenhagen, Copenhagen, Denmark 44d'Hematologie, Hotel-Dieu, Paris, France 55Medicine, University of Oklahoma, Oklahoma City 66NA, NA, NA 77Hypertension and Thrombosis Disease Areas 88Cardiovascular and Urology, GlaxoSmithKline, Philadelphia, United States
How-to-cite Bates SM, Buller H, Lassen MR, Samama MM, Whitsett T, Fischer L, Danoff TM, Froloshki BS, Asbel NR, Ginsberg JS. A PHASE II DOUBLE-BLIND PLACEBO-CONTROLLED PARALLEL-GROUP RANDOMIZED STUDY OF EXTENDED PROPHYLAXIS WITH ODIPARCIL FOLLOWING TOTAL HIP ARTHROPLASTY (THA). J Thromb Haemost 2007; 5 Supplement 2: P-M-653
Introduction: Odiparcil is a novel, orally active antithrombotic agent thought to increase synthesis of glycosaminoglycans with subsequent activation of heparin cofactor II and inhibition of thrombin (IIa).
Methods: In a multicentre adaptive design trial, patients were randomized to 28 days of odiparcil or matching placebo following 7-10 days of prophylactic low molecular weight heparin post THA. In stage 1 of a planned 3 stage trial, safety, tolerability, and antithrombotic effect were assessed using the highest (500 mg BID) and lowest (125 mg BID) doses of odiparcil. Bilateral venography was performed at the end of treatment or early withdrawal. The primary efficacy outcome was a composite of all venous thromboembolic events (VTE), including asymptomatic deep vein thrombosis (DVT), objectively confirmed symptomatic DVT or pulmonary embolism (PE) and death due to VTE; all suspected safety and efficacy events were adjudicated by a blinded independent committee.
Results: A total of 226 patients were randomized and 135 were included in the efficacy analysis. VTE occurred in 4/54 placebo-treated patients (7.41%; 95% CI, 2.06-17.89), 2/38 randomized to low-dose (5.26%; 95% CI, 0.63-17.75), and 1/43 randomized to high-dose odiparcil (2.33%; 95% CI, 0.06-12.29). There were no confirmed PE or deaths. Anti-IIa activity was proportional to odiparcil dose; at steady-state, >75% of patients receiving 500 mg BID achieved trough anti-IIa activity >2ug/mL. One major bleeding event at the surgical site occurred in a patient treated with the highest odiparcil dosage. There were no treatment-emergent cases of elevated AST or ALT >3x upper limit of normal.
Conclusions: Although an unexpectedly low incidence of VTE precluded conclusions about efficacy and continuance into subsequent stages, odiparcil was safe and well-tolerated. Anti-IIa activity achieved levels considered effective based on preclinical models. Further studies will be needed to determine efficacy.