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

Phase 3

Completed

• Conditions: Rheumatic Diseases; Heart Failure; Respiratory Insufficiency; Stroke Acute; Infectious Diseases
• Interventions: Drug: Rivaroxaban, 10 mg; Drug: Placebo; Drug: Rivaroxaban, 7.5 mg

• Registration Number: NCT02111564
• Lead Sponsor: Janssen Research & Development, LLC

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2014-01-07
• Study First Submitted: 2014-03-31
• Study First Submitted QC: 2014-04-09
• Study First Posted: 2014-04-11
• Primary Completion: 2018-03-06
• Study Completion: 2018-05-03
• Disposition First Submitted: 2019-03-05
• Disposition First Submitted QC: 2019-03-05
• Disposition First Posted: 2019-03-08
• Status Verified: 2019-11
• Results First Submitted: 2019-11-05
• Results First Submitted QC: 2019-11-05
• Last Update Submitted: 2019-11-05
• Results First Posted: 2019-11-25
• Last Update Posted: 2019-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12024

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rivaroxaban	Rivaroxaban, 10 mg	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.
Rivaroxaban	Rivaroxaban, 7.5 mg	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.
Placebo	Placebo	Each patient will receive matching placebo tablet once daily orally (by mouth) for 45 days.

Primary Outcome Measures

Name	Time	Method
Event Rate Based on Time From Randomization to the First Occurrence of Major Bleeding Adjudicated by CEC	From randomization to 2 days after the last dose (Day 45)	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.
Time From Randomization to First Occurrence of Composite of All Symptomatic Venous Thromboembolism (VTE) and VTE Related Death Adjudicated by Clinical Event Committee (CEC)	Up to Day 45	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.

Secondary Outcome Measures

Name	Time	Method
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	Up to Day 45	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.
Event Rate Based on Time From Randomization to First Occurrence of VTE-Related Death Adjudicated by CEC	Up to Day 45	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.
Event Rate Based on Time From Randomization to the First Occurrence of a Symptomatic Venous Thromboembolism Event (VTE) Adjudicated by CEC	Up to Day 45	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.
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	Up to Day 45	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.
Event Rate Based on Time From Randomization to First Occurrence of All-Cause Mortality (ACM) Adjudicated by CEC	Up to Day 45	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.