Published Online
on June 18, 2007

A more recent version of this article appeared on July 10, 2007

This Article Free upon publication Full Text (PDF) Data Supplement All Versions of this Article: 116/2/180    most recent CIRCULATIONAHA.106.668020v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Agnelli, G. Search for Related Content PubMed PubMed Citation Articles by Agnelli, G. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB HEPARIN THIOPHENE Related Collections Deep vein thrombosis Coagulation inhibitors Other anticoagulants

Submitted on October 5, 2006
Accepted on April 23, 2007

Treatment of Proximal Deep-Vein Thrombosis With the Oral Direct Factor Xa Inhibitor Rivaroxaban (BAY 59-7939). The ODIXa-DVT (Oral Direct Factor Xa Inhibitor BAY 59-7939 in Patients With Acute Symptomatic Deep-Vein Thrombosis) Study

Giancarlo Agnelli MD^*, Alexander Gallus MB, FRACP, Samuel Z. Goldhaber MD, Sylvia Haas MD, Menno V. Huisman MD, PhD, Russel D. Hull MBBS, MSc, Ajay K. Kakkar MD, PhD, Frank Misselwitz MD, PhD, Sebastian Schellong MD, for the ODIXa-DVT Study Investigators

From the Division of Internal and Cardiovascular Medicine-Stroke Unit, University of Perugia, Perugia, Italy (G.A.); Flinders Medical Centre and Flinders University, Adelaide, Australia (A.G.); Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass (S.Z.G.); Institute for Experimental Oncology and Therapy Research, Munich, Germany (S.H.); Leiden University Medical Center, Leiden, the Netherlands (M.V.H.); Foothills Hospital, Calgary, Alberta, Canada (R.D.H.); Thrombosis Research Institute and Barts and the London School of Medicine, London, United Kingdom (A.K.K.); Bayer HealthCare AG, Wuppertal, Germany (F.M.); and University Hospital Carl Gustav Carus, Dresden, Germany (S.S.).

^* To whom correspondence should be addressed. E-mail: agnellig{at}unipg.it.

Background--An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation. Rivaroxaban (BAY 59-7939) is an oral direct factor Xa inhibitor currently under clinical development.

Methods and Results--This randomized, parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist. Each treatment was administered for 12 weeks. The primary efficacy end point was an improvement in thrombotic burden at day 21 (assessed by quantitative compression ultrasonography; 4-point improvement in thrombus score) without recurrent symptomatic venous thromboembolism or venous thromboembolism-related death. The primary safety end point was major bleeding during 12 weeks of treatment. Outcomes were adjudicated centrally without knowledge of treatment allocation. The primary efficacy end point was achieved in 53 (53.0%) of 100, 58 (59.2%) of 98, 62 (56.9%) of 109, and 49 (43.8%) of 112 patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively, compared with 50 (45.9%) of 109 patients treated with enoxaparin/vitamin K antagonist. There was no significant trend in the dose-response relationship between rivaroxaban BID and the primary efficacy end point (P=0.67). Major bleeding was observed in 1.7%, 1.7%, 3.3%, and 1.7% of patients receiving rivaroxaban 10, 20, or 30 mg BID or 40 mg once daily, respectively. There were no major bleeding events with enoxaparin/vitamin K antagonist.

Conclusions--Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban, because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing.

Key words: thrombosis • thromboembolism • deep-vein thrombosis • factor Xa • anticoagulants

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