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Venous Thromboembolic Event (VTE) Prophylaxis in Medically Ill Patients (MAGELLAN)

This study has been completed.
Sponsor:
Collaborator:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00571649
First received: December 11, 2007
Last updated: August 3, 2016
Last verified: August 2016
Results First Received: February 16, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition: Venous Thromboembolism
Interventions: Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Enoxaparin
Drug: Rivaroxaban placebo
Drug: Enoxaparin placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient first visit date: 04 DEC 2007; last patient last visit date 24 NOV 2010. Primary completion date: 12 AUG 2010. Participants were aged ≥40 years, hospitalized for an acute medical illness, and at risk of Venous Thromboembolism (VTE) (with heart failure, cancer, ischemic stroke, infection or inflammation, or respiratory insufficiency)

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 8428 participants were screened; 327 failed. 8101 were randomized. 7998 (98.7%) were in the Safety Analysis Set (SAF), i.e. received study medication. 6024 (74.4%) were in the modified Intent to Treat (at Day 35) group (valid for SAF with adequate assessment of venous thromboembolism). A total of 6005 (74.1%) completed study.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) 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 during treatment period
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days during treatment period

Participant Flow for 2 periods

Period 1:   Treatment Period
    Rivaroxaban (Xarelto, BAY59-7939)   Enoxaparin
STARTED   4050   4051 
Participants Received Treatment   3997   4001 
Day 10   3454   3499 
Day 35   3033   3115 
COMPLETED   2958   3047 
NOT COMPLETED   1092   1004 
Adverse Event                438                385 
Clinical endpoint reached                50                56 
Withdrawal by Subject                285                255 
Death                76                59 
Physician Decision                8                9 
Lost to Follow-up                43                41 
Non-compliant with study medication                88                89 
Patient convenience                11                13 
Protocol Violation                90                92 
Technical problems                3                5 

Period 2:   Follow-up Period
    Rivaroxaban (Xarelto, BAY59-7939)   Enoxaparin
STARTED   3583 [1]   3635 [1] 
COMPLETED   3038 [2]   3107 [2] 
NOT COMPLETED   545   528 
Adverse Event                46                40 
Clinical endpoint reached                5                2 
Withdrawal by Subject                119                115 
Death                132                133 
Physician Decision                7                13 
Lost to Follow-up                95                92 
Patient convenience                136                121 
Protocol Violation                5                12 
[1] Participants were required to enter follow-up even if treatment period not completed.
[2] Began day after last dose study drug; ended on Day 90 (+/- 7 days) .



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) 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 (SAF population)
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days (SAF population)
Total Total of all reporting groups

Baseline Measures
   Rivaroxaban (Xarelto, BAY59-7939)   Enoxaparin   Total 
Overall Participants Analyzed 
[Units: Participants]
 3997   4001   7998 
Age 
[Units: Years]
Mean (Standard Deviation)
 69.2  (11.9)   69.2  (11.7)   69.2  (11.8) 
Age, Customized 
[Units: Participants]
     
< 65 years   1323   1363   2686 
65 to < 75 years   1144   1090   2234 
>= 75 years   1530   1548   3078 
Gender 
[Units: Participants]
     
Female   1774   1898   3672 
Male   2223   2103   4326 
Race 
[Units: Participants]
     
White   2749   2744   5493 
Black   89   92   181 
Asian   793   794   1587 
Native American   12   12   24 
Hispanic   69   70   139 
Uncodable   106   112   218 
Unknown   1   0   1 
Missing   178   177   355 
Reason for hospitalization [1] 
[Units: Participants]
     
Heart failure (NYHA Class III or NYHA Class IV)   1292   1301   2593 
Active cancer   294   290   584 
Acute ischemic stroke   691   692   1383 
Acute Infectious and Inflammatory Diseases   1904   1876   3780 
Acute infectious disease   1826   1801   3627 
Acute inflammatory or rheumatic disease   150   149   299 
Acute respiratory insufficiency   1085   1151   2236 
[1] Participants may have more than one acute condition as hospitalization reason. Acute medical illnesses included heart failure (New York Heart Association [NYHA] Class III [marked limitation of physical activity] or NYHA Class IV [inability to carry out any physical activity without discomfort)] active cancer, acute ischemic stroke, acute infectious and inflammatory diseases (including acute rheumatic diseases), acute respiratory insufficiency.


  Outcome Measures
  Show All Outcome Measures

1.  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   [ Time Frame: Up to Day 35 + 6 days ]

2.  Primary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and VTE-related Death up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

3.  Secondary:   Percentage of Participants With Composite Endpoint of VTE (Any DVT, Non Fatal PE) and All-cause Mortality up to Day 35 + 6 Days   [ Time Frame: Up to Day 35 + 6 days ]

4.  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   [ Time Frame: Up to Day 10 + 5 days ]

5.  Secondary:   Percentage of Participants With VTE Combined With All-cause Mortality up to Day 10 + 5 Days   [ Time Frame: Up to Day 10 + 5 days ]

6.  Secondary:   Percentage of Participants With Symptomatic VTE, Including and Excluding VTE-related Death up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

7.  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   [ Time Frame: Up to Day 35 + 6 days ]

8.  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   [ Time Frame: Up to Day 10 + 5 days ]

9.  Secondary:   Percentage of Participants With Major Vascular Events up to Days 10, 35, and 90   [ Time Frame: At Day 10 + 5 days, at Day 35 + 6 days, and at Day 90 + 7 days ]

10.  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   [ Time Frame: Up to Day 35 + 6 days ]

11.  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   [ Time Frame: Up to Day 10 + 5 days ]
  Hide Outcome Measure 11

Measure Type Secondary
Measure Title 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
Measure Description 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.
Time Frame Up to Day 10 + 5 days  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Per Protocol Day 10: participant was valid for the safety analysis, had an adequate assessment of VTE up to Day 10 not later than 48 hours after stop of study drug, met inclusion criteria, and had no major protocol deviations

Reporting Groups
  Description
Rivaroxaban (Xarelto, BAY59-7939) 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
Enoxaparin Participants received oral rivaroxaban-matched placebo tablet OD for 35 +/- 4 days, plus 40 mg subcutaneous enoxaparin solution OD for 10 +/- 4 days

Measured Values
   Rivaroxaban (Xarelto, BAY59-7939)   Enoxaparin 
Participants Analyzed 
[Units: Participants]
 2938   2993 
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 
[Units: Percentage of participants]
   
Symptomatic non-fatal PE   0.2   0.1 
Symptomatic DVT in lower extremity   0.2   0.2 
Asymptomatic proximal DVT in lower extremity   2.4   2.4 
VTE related death   0.1   0.2 

No statistical analysis provided for 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



12.  Secondary:   Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days   [ Time Frame: Up to Day 90 + 7 days ]

13.  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)   [ Time Frame: Up to Day 35 + 6 days ]

14.  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)   [ Time Frame: Up to Day 10 + 5 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
A heterogeneous population (with different acute medical illnesses and severity of illness) was included in the trial. VTE risk in acute medical illnesses is moderate [with no thromboprophylaxis] .


  More Information