title: 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.
abstract: 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.
  
  
  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; > or = 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.
authors.affiliation: Division of Internal and Cardiovascular Medicine, University of Perugia, Ospedale S. Maria della Misericordia, Perugia, Italy. agnellig@unipg.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Alexander
authors.initials: A
authors.lastname: Gallus
authors.forename: Samuel Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: Sylvia
authors.initials: S
authors.lastname: Haas
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.forename: Russel D
authors.initials: RD
authors.lastname: Hull
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Kakkar
authors.forename: Frank
authors.initials: F
authors.lastname: Misselwitz
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schellong
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D065427:Factor Xa Inhibitors; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D018579:Patient Selection; D011655:Pulmonary Embolism / Q000175:diagnosis; D000069552:Rivaroxaban; D012449:Safety; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013927:Thrombosis / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D009025:Morpholines; D013876:Thiophenes; D006493:Heparin; D000069552:Rivaroxaban