Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients

Study Overview
=================
Brief Summary
-----------------
This study will evaluate if extended therapy with oral rivaroxaban can prevent blood clots in the leg and lung that can occur with patients hospitalized for acute medical illness, and compare these results with those of the standard enoxaparin dose and duration regimen. The safety of rivaroxaban will also be studied.

Detailed Description
-----------------
The treatment period was followed by a follow-up period starting the day after the last intake of study medication, regardless of the actual duration of study drug administration and ended on Day 90 (+ 7 days). Participants who did not complete the treatment period also entered the follow-up period. It was also possible that participants did not enter the follow-up period, e.g. due to withdrawal of consent or termination of study participation. Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

Official Title
-----------------
Multicenter, Randomized, Parallel-group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Medically Ill Patients Comparing Rivaroxaban With Enoxaparin. The MAGELLAN Study

Conditions
-----------------
Venous Thromboembolism

Intervention / Treatment
-----------------
* Drug: Rivaroxaban (Xarelto, BAY59-7939)
* Drug: Enoxaparin
* Drug: Rivaroxaban placebo
* Drug: Enoxaparin placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female patients aged 40 years or more Patients at risk of venous thromboembolic events being hospitalized for acute medical conditions as follows: Heart failure, New York Heart Association (NYHA) class III or IV Active cancer Acute ischemic stroke Acute infectious and inflammatory diseases, including acute rheumatic diseases Acute respiratory insufficiency Additional risk factor for VTE, including reduced mobility Exclusion Criteria: Conditions that contraindicate the use of antithrombotic therapy with the Low Molecular-Weight Heparin (LMWH) enoxaparin Conditions that may increase the risk of bleeding, including intracranial hemorrhage Required drugs or procedures which may interfere with the study treatment Concomitant conditions or diseases which may increase the risk of study subjects or interfere with the study outcome General conditions in which subjects are not suitable to participate in the study

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivaroxaban (Xarelto, BAY59-7939)<br>Participants received 10 mg oral rivaroxaban tablet once daily (OD) for 35 +/- 4 days, plus subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days | Drug: Rivaroxaban (Xarelto, BAY59-7939)<br>* Oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days<br>Drug: Enoxaparin placebo<br>* Subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days<br>|
| Active Comparator: Enoxaparin<br>Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days | Drug: Enoxaparin<br>* Subcutaneous enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days<br>Drug: Rivaroxaban placebo<br>* Oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Composite Endpoint of Venous Thromboembolism [VTE] (Any Deep Vein Thrombosis [DVT], Non Fatal Pulmonary Embolism [PE]) and VTE-related Death up to Day 35 + 6 Days | A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death. | Up to Day 35 + 6 days | 
| Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days | A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death. | Up to Day 10 + 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days | A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related). | Up to Day 35 + 6 days | 
| Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days Per mITT Population | A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death. | Up to Day 10 + 5 days | 
| Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days | A composite endpoint of: asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and death (VTE-related and not VTE-related). | Up to Day 10 + 5 days | 
| Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90 | Symptomatic VTE (non-fatal PE and DVT in lower extremity), including and excluding VTE-related death (PE and PE cannot be excluded) up to Days 10, 35, and 90 | At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days | 
| Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 35 + 6 Days | Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events. | Up to Day 35 + 6 days | 
| Percentage of Participants With Net Clinical Benefit (Any DVT, Non-fatal PE, VTE-related Death, Plus Major and Clinically Relevant Non-major Bleeding Events) up to Day 10 + 5 Days | Net clinical benefit is a composite of the primary efficacy endpoint (asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death) plus major and clinically relevant non-major bleeding events | Up to Day 10 + 5 days | 
| Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90 | Major vascular events included cardiovascular death, acute myocardial infarction (MI), or acute ischemic stroke. Participants may have had a vascular event in more than one category. | At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days | 
| Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 35 + 6 Days | The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death. | Up to Day 35 + 6 days | 
| Percentage of Participants With Each Component of the Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days | The components of the composite endpoint include asymptomatic proximal DVT in lower extremity detected by mandatory bilateral lower extremity venous ultrasonography; symptomatic DVT in lower extremity, proximal or distal; symptomatic, non-fatal PE; and VTE-related death. | Up to Day 10 + 5 days | 
| Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days | All deaths, including VTE-related deaths, cardiovascular deaths, and other deaths. | Up to Day 90 + 7 days | 
| Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Intake of Any Study Medication (Day 35 + 6 Days) | Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin; or transfusion of >= 2 units of packed RBCs (Red blood cells) or whole blood; or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding | Up to Day 35 + 6 days | 
| Percentage of Participants With the Composite of Treatment Emergent Major Bleeding Events and Non-major Clinically Relevant Bleeding Events up to 2 Days After Last Application of a Study Medication Syringe (Day 10 + 5 Days) | Major bleeding events were defined as events leading to >=2 g/dL fall in hemoglobin or transfusion of >=2 units of packed RBCs or whole blood or leading to death. Non-major bleeding events were defined as overt bleeding not meeting the criteria of major bleeding. | Up to Day 10 + 5 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute medical illnesses with increased risk for VTE., Deep vein thrombosis (DVT), Pulmonary embolism (PE),, Venous Thromboembolic disease (VTE),, Medical illness