A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein-DVT Dose-Ranging Study.
We performed a randomized dose-ranging study, double-blind for rivaroxaban doses and open-label for the comparator (low-molecular-weight heparin followed by vitamin K antagonists) to assess the optimal dose of rivaroxaban for the treatment of deep vein thrombosis. A total of 543 patients with acute deep-venous thrombosis received rivaroxaban 20, 30, or 40 mg once daily or comparator. Treatment lasted for 84 days. The primary efficacy outcome was the 3-month incidence of the composite of symptomatic venous thromboembolic complications and asymptomatic deterioration in thrombotic burden as assessed by comparison of ultrasound and perfusion lung scanning at day 84 with baseline. The main safety outcome was the composite of major bleeding and clinically relevant nonmajor bleeding. A total of 449 (83%) of the 543 patients could be included in the per-protocol population. The primary efficacy outcome occurred in 6.1%, 5.4%, and 6.6% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 9.9% of those receiving standard therapy. The main safety outcome occurred in 5.9%, 6.0%, and 2.2% of the rivaroxaban 20-, 30-, and 40-mg treatment groups, respectively, and in 8.8% of those receiving standard therapy. These results with simple fixed-dose oral regimens justify phase 3 evaluations (www.ClinicalTrials.gov no.NCT00395772).
Buller
Harry R
HR
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. h.r.buller@amc.uva.nl
Lensing
Anthonie W A
AW
Prins
Martin H
MH
Agnelli
Giancarlo
G
Cohen
Alexander
A
Gallus
Alexander S
AS
Misselwitz
Frank
F
Raskob
Gary
G
Schellong
Sebastian
S
Segers
Annelise
A
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage*; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage*; D016896:Treatment Outcome; D014463:Ultrasonography; D020246:Venous Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy*
D009025:Morpholines; D013876:Thiophenes; D000990:Antithrombin III; D000069552:Rivaroxaban