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Thromb Haemost 2016; 115(06): 1240-1248
DOI: 10.1160/TH15-09-0756
Trial Protocol Design Paper
Schattauer GmbH

The MARINER trial[*] of rivaroxaban after hospital discharge for medical patients at high risk of VTE

Design, rationale, and clinical implications
Gary E. Raskob
1   University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City, Oklahoma, USA
,
Alex C. Spyropoulos
2   Anticoagulation and Clinical Thrombosis Services North Shore–LlJ Health System, Hofstra North Shore-LIJ School of Medicine, Manhasset, New York, USA
,
Julie Zrubek
3   Janssen Research & Development, LLC, Raritan, New Jersey, USA
,
Walter Ageno
4   Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
Gregory Albers
5   Stanford Stroke Center, Department of Neurology and Neurological Sciences, Stanford University, Stanford, California, USA
,
C. Gregory Elliott
6   Department of Medicine, Intermountain Medical Center and the University of Utah, Murray, Utah, USA
,
Jonathan Halperin
7   Icahn School of Medicine at Mount Sinai, New York, New York, USA
,
Lloyd Haskell
3   Janssen Research & Development, LLC, Raritan, New Jersey, USA
,
William R. Hiatt
8   Division of Cardiology, University of Colorado School of Medicine and CPC Clinical Research, Aurora, Colorado, USA
,
Gregory A. Maynard
9   University of California Davis Medical Center, Sacramento, California, USA
,
Gary Peters
3   Janssen Research & Development, LLC, Raritan, New Jersey, USA
,
Theodore Spiro
10   Bayer HealthCare Pharmaceuticals Inc, Whippany, New Jersey, USA
,
Philippe Gabriel Steg
11   Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France
,
Eun Young Suh
3   Janssen Research & Development, LLC, Raritan, New Jersey, USA
,
Jeffrey I. Weitz
12   McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada
› Author Affiliations Financial support: This study is supported by Janssen Research & Development, LLC.
Further Information

Publication History

Received: 25 September 2015

Accepted after major revision: 16 February 2015

Publication Date:
28 November 2017 (online)

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Summary

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.

Keywords

Venous thromboembolism - anticoagulants - deep-vein thrombosis - pulmonary embolism - thromboprophylaxis - rivaroxaban - medical patients

* ClinicalTrials.gov Identifier: NCT02111564


 

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