A Study of Rivaroxaban (JNJ-39039039) on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients

Heart Failure Clinical Trial

— MARINER  

Official title:

Medically Ill Patient Assessment of Rivaroxaban Versus Placebo in Reducing Post-Discharge Venous Thrombo-Embolism Risk

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02111564
• Other study ID #: CR103834
• Secondary ID: 2014-000305-13RI
• Status: Completed
• Phase: Phase 3
• Start date: January 7, 2014
• Est. completion date: May 3, 2018

Study information

• Verified date: November 2019
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of rivaroxaban compared with placebo in the prevention of symptomatic venous thromboembolism (VTE) events and VTE-related death post-hospital discharge in high-risk, medically ill patients.

Description:

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect)-controlled, event-driven, multicenter study in patients who are hospitalized for a specific acute medical illness and have other risk factors for venous thromboembolism (VTE). The study is designed to evaluate rivaroxaban in the prevention of symptomatic VTE events and VTE-related deaths for a period of 45 days post-hospital discharge. The study will consist of a screening phase, a 45-day double-blind treatment phase, and a 30-day follow-up phase. Study drug will start at randomization (Day 1), and will continue until Day 45 (inclusive). A total of approximately 12000 patients will be randomly assigned to either rivaroxaban or placebo in a 1:1 ratio. The total duration for a patient who completes the study after randomization is expected to be 75 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12024
• Est. completion date: May 3, 2018
• Est. primary completion date: March 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Key Inclusion Criteria:

• The duration of the index hospitalization must have been at least 3 and no more than 10 consecutive days

• Must meet venous thromboembolism (VTE) risk criteria with a total modified Improve VTE Risk Score of: greater than or equal 4, or 3 with D-dimer > 2* upper limit of normal (ULN), or 2 with D-dimer > 2*ULN

Key Exclusion Criteria:

• Any serious bleeding within 3 months prior to randomization or occurring during index hospitalization

• Serious trauma (including head trauma) within 4 weeks before randomization

• History of hemorrhagic stroke at any time in the past

• Any medical condition that requires chronic use of any parenteral or oral anticoagulation

Related Conditions & MeSH terms

• Collagen Diseases
• Communicable Diseases
• Heart Failure
• Infection
• Infectious Diseases
• Pulmonary Valve Insufficiency
• Respiratory Insufficiency
• Rheumatic Diseases
• Stroke Acute

Intervention

Drug:
• Rivaroxaban, 10 mg
Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening greater than or equal to (>=)50 mL/min will receive 10 mg rivaroxaban tablet with or without food.
• Rivaroxaban, 7.5 mg
Patients, randomly allocated to the rivaroxaban arm, with a creatinine clearance at screening from >=30 to less than (<)50 mL/min will receive 7.5 mg rivaroxaban tablet with or without food.
• Placebo
All patients, randomly allocated to the placebo arm, will receive one placebo tablet with or without food.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC	Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Colombia,  Croatia,  Czechia,  Denmark,  Estonia,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Latvia,  Lithuania,  Mexico,  Netherlands,  North Macedonia,  Peru,  Poland,  Portugal,  Puerto Rico,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Raskob GE, Spyropoulos AC, Zrubek J, Ageno W, Albers G, Elliott CG, Halperin J, Haskell L, Hiatt WR, Maynard GA, Peters G, Spiro T, Steg PG, Suh EY, Weitz JI. The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications. Thromb Haemost. 2016 Jun 2;115(6):1240-8. doi: 10.1160/TH15-09-0756. Epub 2016 Feb 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time From Randomization to First Occurrence of Composite of All Symptomatic Venous Thromboembolism (VTE) and VTE Related Death Adjudicated by Clinical Event Committee (CEC)	Symptomatic VTE included lower extremity deep vein thrombosis (DVT) and non-fatal pulmonary embolism (PE). Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45
Primary	Event Rate Based on Time From Randomization to the First Occurrence of Major Bleeding Adjudicated by CEC	A major bleeding event was defined using validated International Society on Thrombosis and Haemostasis (ISTH) bleeding criteria. A major bleeding event was defined as overt bleeding that was associated with a fall in hemoglobin of 2 gram per deciliter (g/dL) or more, or a transfusion of 2 or more units of packed red blood cells or whole blood, or a critical site defined as intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or a fatal outcome. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or last dose + 2 days.	From randomization to 2 days after the last dose (Day 45)
Secondary	Event Rate Based on Time From Randomization to First Occurrence of VTE-Related Death Adjudicated by CEC	Event rate based on time from randomization to first occurrence of VTE-related death (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45
Secondary	Event Rate Based on Time From Randomization to the First Occurrence of a Symptomatic Venous Thromboembolism Event (VTE) Adjudicated by CEC	Event rate based on time from randomization to the first occurrence of a symptomatic VTE (adjudicated by CEC) was assessed. Symptomatic VTE included lower extremity DVT and non-fatal PE. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45
Secondary	Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE and All-Cause Mortality (ACM) Adjudicated by CEC	Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE and ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45
Secondary	Event Rate Based on Time From Randomization to the First Occurrence of a Composite of Symptomatic VTE, Myocardial Infarction (MI), Non-Hemorrhagic Stroke, and Cardiovascular (CV) Death Adjudicated by CEC	Event rate based on time from randomization to the first occurrence of a composite of symptomatic VTE (lower extremity DVT and non-fatal PE), MI, non-hemorrhagic stroke, and CV death (death due to a known CV cause and death in which a CV cause cannot be ruled out; by this definition, a VTE-related death was considered a CV death) as adjudicated by CEC was reported. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45
Secondary	Event Rate Based on Time From Randomization to First Occurrence of All-Cause Mortality (ACM) Adjudicated by CEC	Event rate based on time from randomization to first occurrence of ACM (adjudicated by CEC) was assessed. Event rate was defined as number of events per 100 participants in 45 days of follow up. Participants who did not have events were censored on the minimum of last visit before or on death, or Day 45.	Up to Day 45