title: The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications.
abstract: Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo-controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D-dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl ≥ 50 ml/min, or 7.5 mg once daily for patients with CrCl ≥ 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events.
authors: Gary E. Raskob, PhD, Dean, College of Public Health and Regents' Professor, Epidemiology and Medicine, University of Oklahoma Health Sciences Center, College of Public Health, 801 NE 13th Street, Oklahoma City, OK 73104, USA, Tel.: +1 405 271 2232, Fax: +1 405 271 3039, E-mail: gary-raskob@ouhsc.edu.
authors: Gary E
authors: GE
authors: Raskob
authors: Alex C
authors: AC
authors: Spyropoulos
authors: Julie
authors: J
authors: Zrubek
authors: Walter
authors: W
authors: Ageno
authors: Gregory
authors: G
authors: Albers
authors: C Gregory
authors: CG
authors: Elliott
authors: Jonathan
authors: J
authors: Halperin
authors: Lloyd
authors: L
authors: Haskell
authors: William R
authors: WR
authors: Hiatt
authors: Gregory A
authors: GA
authors: Maynard
authors: Gary
authors: G
authors: Peters
authors: Theodore
authors: T
authors: Spiro
authors: Philippe Gabriel
authors: PG
authors: Steg
authors: Eun Young
authors: EY
authors: Suh
authors: Jeffrey I
authors: JI
authors: Weitz
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012307:Risk Factors; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D054556:Venous Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D000069552:Rivaroxaban
keywords: Venous thromboembolism; anticoagulants; deep-vein thrombosis; medical patients; pulmonary embolism; rivaroxaban; thromboprophylaxis