Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients

Venous Thromboembolism Clinical Trial

— MAGELLAN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00571649
• Other study ID #: 12839
• Secondary ID: 2007-004614-14
• Status: Completed
• Phase: Phase 3
• First received: December 11, 2007
• Last updated: November 28, 2014
• Start date: December 2007
• Est. completion date: November 2010

Study information

• Verified date: November 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8101
• Est. completion date: November 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban (Xarelto, BAY59-7939)
Oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days
• Enoxaparin
Subcutaneous enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days
• Rivaroxaban placebo
Oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days
• Enoxaparin placebo
Subcutaneous enoxaparin-matched placebo solution OD for 10 +/- 4 days

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Czech Republic,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hong Kong,  Hungary,  India,  Indonesia,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Lithuania,  Luxembourg,  Malaysia,  Mexico,  Netherlands,  New Zealand,  Norway,  Pakistan,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  Singapore,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (4)

Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos A, Tapson V. Extended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol. J Thromb Thrombolysis. 2011 May;31 — View Citation

Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013 Feb 7;368(6):513-23. doi: 10. — View Citation

Mebazaa A, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Merli G, Schellong SW, Spyropoulos AC, Tapson VF, De Sanctis Y, Cohen AT. Predicting the risk of venous thromboembolism in patients hospitalized with heart failure. Circulation. 2014 Jul 29;130(5):4 — View Citation

Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does it improve outcomes? J Thromb Haemost. 2012 Oct;10(10):2053-60. doi: 10.1111/j.1538-7836.2012.04874.x. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	Yes
Secondary	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	Yes

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