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:
Bayer
ClinicalTrials.gov Identifier:
NCT00571649
First received: December 11, 2007
Last updated: June 13, 2013
Last verified: June 2013
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  
Number of Participants  
[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
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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 ]

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

Measure Type Secondary
Measure Title Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days
Measure Description All deaths, including VTE-related deaths, cardiovascular deaths, and other deaths.
Time Frame Up to Day 90 + 7 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.
Safety population: Participant had at least one dose of study drug.

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  
Number of Participants Analyzed  
[units: participants]
  3997     4001  
Percentage of Participants With All-cause Mortality up to Day 90 + 7 Days  
[units: Percentage¬†of¬†participants]
   
Any event     6.7     6.2  
Death (cardiovascular)     1.4     1.4  
Death (other)     4.3     3.7  
VTE related death     1.0     1.1  

No statistical analysis provided for Percentage of Participants With All-cause Mortality 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


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Limitations and Caveats
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] .  


Results Point of Contact:  
Name/Title: Therapeutic Area Head
Organization: BAYER
e-mail: clinical-trials-contact@bayerhealthcare.com


Publications of Results:

Responsible Party: Therapeutic Area Head, Bayer HealthCare Pharmaceuticals Inc.
ClinicalTrials.gov Identifier: NCT00571649     History of Changes
Other Study ID Numbers: 12839, 2007-004614-14
Study First Received: December 11, 2007
Results First Received: February 16, 2012
Last Updated: June 13, 2013
Health Authority: United States: Food and Drug Administration