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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Heart Failure, Respiratory Insufficiency, Stroke Acute, Infectious Diseases, Rheumatic Diseases

Intervention / Treatment
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* Drug: Rivaroxaban, 10 mg
* Drug: Rivaroxaban, 7.5 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban<br>Each patient will receive either 10 mg or 7.5 mg rivaroxaban tablet once daily orally (by mouth) for 45 days. The dosing will depend on a creatinine clearance at screening. | Drug: Rivaroxaban, 10 mg<br>* 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.<br>* Other names: BAY59-7939;Drug: Rivaroxaban, 7.5 mg<br>* 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.<br>* Other names: BAY59-7939;|
| Placebo Comparator: Placebo<br>Each patient will receive matching placebo tablet once daily orally (by mouth) for 45 days. | Drug: Placebo<br>* All patients, randomly allocated to the placebo arm, will receive one placebo tablet with or without food.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Respiratory Insufficiency, Stroke Acute, Infectious Diseases, Rheumatic Diseases, Medically ill Patient, Rivaroxaban, Thromboembolism, Prophylactic Anti-Coagulation