Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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 ]

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
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   0.5  

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

Other Adverse Events
    Rivaroxaban (Xarelto, BAY59-7939)   Enoxaparin
Total, other (not including serious) adverse events     
# participants affected / at risk   2297/3997 (57.47%)   2291/4001 (57.26%) 
Blood and lymphatic system disorders     
Anaemia * 1     
# participants affected / at risk   87/3997 (2.18%)   85/4001 (2.12%) 
# events   93   87 
Neutropenia * 1     
# participants affected / at risk   20/3997 (0.50%)   16/4001 (0.40%) 
# events   32   20 
Thrombocytopenia * 1     
# participants affected / at risk   29/3997 (0.73%)   25/4001 (0.62%) 
# events   32   27 
Cardiac disorders     
Atrial fibrillation * 1     
# participants affected / at risk   74/3997 (1.85%)   61/4001 (1.52%) 
# events   82   65 
Cardiac failure * 1     
# participants affected / at risk   43/3997 (1.08%)   38/4001 (0.95%) 
# events   46   44 
Mitral valve incompetence * 1     
# participants affected / at risk   36/3997 (0.90%)   32/4001 (0.80%) 
# events   36   33 
Tachycardia * 1     
# participants affected / at risk   32/3997 (0.80%)   43/4001 (1.07%) 
# events   33   49 
Tricuspid valve incompetence * 1     
# participants affected / at risk   19/3997 (0.48%)   22/4001 (0.55%) 
# events   19   22 
Ventricular extrasystoles * 1     
# participants affected / at risk   24/3997 (0.60%)   17/4001 (0.42%) 
# events   26   17 
Ear and labyrinth disorders     
Vertigo * 1     
# participants affected / at risk   26/3997 (0.65%)   25/4001 (0.62%) 
# events   26   26 
Eye disorders     
Conjunctivitis * 1     
# participants affected / at risk   16/3997 (0.40%)   24/4001 (0.60%) 
# events   16   24 
Gastrointestinal disorders     
Abdominal pain * 1     
# participants affected / at risk   89/3997 (2.23%)   56/4001 (1.40%) 
# events   109   64 
Abdominal pain upper * 1     
# participants affected / at risk   59/3997 (1.48%)   53/4001 (1.32%) 
# events   63   62 
Constipation * 1     
# participants affected / at risk   362/3997 (9.06%)   346/4001 (8.65%) 
# events   418   375 
Diarrhoea * 1     
# participants affected / at risk   214/3997 (5.35%)   230/4001 (5.75%) 
# events   238   256 
Dyspepsia * 1     
# participants affected / at risk   53/3997 (1.33%)   62/4001 (1.55%) 
# events   54   69 
Gastritis * 1     
# participants affected / at risk   36/3997 (0.90%)   38/4001 (0.95%) 
# events   37   38 
Gastritis erosive * 1     
# participants affected / at risk   20/3997 (0.50%)   19/4001 (0.47%) 
# events   21   19 
Gingival bleeding * 1     
# participants affected / at risk   20/3997 (0.50%)   9/4001 (0.22%) 
# events   22   9 
Hiatus hernia * 1     
# participants affected / at risk   20/3997 (0.50%)   16/4001 (0.40%) 
# events   20   16 
Nausea * 1     
# participants affected / at risk   207/3997 (5.18%)   226/4001 (5.65%) 
# events   242   253 
Vomiting * 1     
# participants affected / at risk   170/3997 (4.25%)   149/4001 (3.72%) 
# events   205   175 
Haemorrhoidal haemorrhage * 1     
# participants affected / at risk   22/3997 (0.55%)   12/4001 (0.30%) 
# events   23   12 
General disorders     
Asthenia * 1     
# participants affected / at risk   52/3997 (1.30%)   31/4001 (0.77%) 
# events   54   32 
Chest pain * 1     
# participants affected / at risk   89/3997 (2.23%)   77/4001 (1.92%) 
# events   102   82 
Fatigue * 1     
# participants affected / at risk   33/3997 (0.83%)   35/4001 (0.87%) 
# events   35   35 
Injection site haemorrhage * 1     
# participants affected / at risk   8/3997 (0.20%)   21/4001 (0.52%) 
# events   8   23 
Oedema peripheral * 1     
# participants affected / at risk   132/3997 (3.30%)   115/4001 (2.87%) 
# events   153   127 
Pain * 1     
# participants affected / at risk   42/3997 (1.05%)   39/4001 (0.97%) 
# events   46   40 
Pyrexia * 1     
# participants affected / at risk   132/3997 (3.30%)   131/4001 (3.27%) 
# events   158   162 
Hepatobiliary disorders     
Cholelithiasis * 1     
# participants affected / at risk   49/3997 (1.23%)   47/4001 (1.17%) 
# events   50   48 
Hepatic function abnormal * 1     
# participants affected / at risk   17/3997 (0.43%)   24/4001 (0.60%) 
# events   18   24 
Hepatic steatosis * 1     
# participants affected / at risk   48/3997 (1.20%)   61/4001 (1.52%) 
# events   48   61 
Infections and infestations     
Bronchitis * 1     
# participants affected / at risk   64/3997 (1.60%)   47/4001 (1.17%) 
# events   65   48 
Cellulitis * 1     
# participants affected / at risk   22/3997 (0.55%)   18/4001 (0.45%) 
# events   22   19 
Nasopharyngitis * 1     
# participants affected / at risk   37/3997 (0.93%)   36/4001 (0.90%) 
# events   38   36 
Oral candidiasis * 1     
# participants affected / at risk   31/3997 (0.78%)   34/4001 (0.85%) 
# events   31   35 
Pneumonia * 1     
# participants affected / at risk   73/3997 (1.83%)   65/4001 (1.62%) 
# events   75   68 
Upper respiratory tract infection * 1     
# participants affected / at risk   30/3997 (0.75%)   26/4001 (0.65%) 
# events   33   27 
Urinary tract infection * 1     
# participants affected / at risk   138/3997 (3.45%)   142/4001 (3.55%) 
# events   148   151 
Injury, poisoning and procedural complications     
Fall * 1     
# participants affected / at risk   33/3997 (0.83%)   40/4001 (1.00%) 
# events   38   40 
Contusion * 1     
# participants affected / at risk   38/3997 (0.95%)   42/4001 (1.05%) 
# events   50   63 
Investigations     
Alanine aminotransferase increased * 1     
# participants affected / at risk   32/3997 (0.80%)   61/4001 (1.52%) 
# events   32   66 
Aspartate aminotransferase increased * 1     
# participants affected / at risk   23/3997 (0.58%)   35/4001 (0.87%) 
# events   23   36 
Blood creatinine increased * 1     
# participants affected / at risk   38/3997 (0.95%)   36/4001 (0.90%) 
# events   40   39 
Blood urea increased * 1     
# participants affected / at risk   24/3997 (0.60%)   23/4001 (0.57%) 
# events   27   24 
Creatinine renal clearance decreased * 1     
# participants affected / at risk   36/3997 (0.90%)   35/4001 (0.87%) 
# events   40   35 
Gamma-glutamyltransferase increased * 1     
# participants affected / at risk   31/3997 (0.78%)   32/4001 (0.80%) 
# events   31   32 
Haemoglobin decreased * 1     
# participants affected / at risk   23/3997 (0.58%)   12/4001 (0.30%) 
# events   26   12 
Metabolism and nutrition disorders     
Dehydration * 1     
# participants affected / at risk   43/3997 (1.08%)   30/4001 (0.75%) 
# events   49   30 
Diabetes mellitus * 1     
# participants affected / at risk   39/3997 (0.98%)   34/4001 (0.85%) 
# events   40   34 
Hyperglycaemia * 1     
# participants affected / at risk   46/3997 (1.15%)   50/4001 (1.25%) 
# events   54   63 
Hyperkalaemia * 1     
# participants affected / at risk   62/3997 (1.55%)   51/4001 (1.27%) 
# events   66   57 
Hypoglycaemia * 1     
# participants affected / at risk   37/3997 (0.93%)   39/4001 (0.97%) 
# events   46   48 
Hypokalaemia * 1     
# participants affected / at risk   191/3997 (4.78%)   184/4001 (4.60%) 
# events   219   219 
Hyponatraemia * 1     
# participants affected / at risk   35/3997 (0.88%)   34/4001 (0.85%) 
# events   38   34 
Decreased appetite * 1     
# participants affected / at risk   38/3997 (0.95%)   40/4001 (1.00%) 
# events   42   44 
Musculoskeletal and connective tissue disorders     
Arthralgia * 1     
# participants affected / at risk   62/3997 (1.55%)   76/4001 (1.90%) 
# events   68   87 
Back pain * 1     
# participants affected / at risk   97/3997 (2.43%)   82/4001 (2.05%) 
# events   105   85 
Muscle spasms * 1     
# participants affected / at risk   25/3997 (0.63%)   28/4001 (0.70%) 
# events   25   30 
Musculoskeletal pain * 1     
# participants affected / at risk   46/3997 (1.15%)   61/4001 (1.52%) 
# events   50   66 
Neck pain * 1     
# participants affected / at risk   14/3997 (0.35%)   22/4001 (0.55%) 
# events   14   25 
Osteoarthritis * 1     
# participants affected / at risk   29/3997 (0.73%)   22/4001 (0.55%) 
# events   30   24 
Pain in extremity * 1     
# participants affected / at risk   110/3997 (2.75%)   103/4001 (2.57%) 
# events   127   113 
Nervous system disorders     
Dizziness * 1     
# participants affected / at risk   81/3997 (2.03%)   72/4001 (1.80%) 
# events   83   80 
Headache * 1     
# participants affected / at risk   205/3997 (5.13%)   185/4001 (4.62%) 
# events   237   221 
Syncope * 1     
# participants affected / at risk   23/3997 (0.58%)   19/4001 (0.47%) 
# events   24   21 
Psychiatric disorders     
Anxiety * 1     
# participants affected / at risk   89/3997 (2.23%)   94/4001 (2.35%) 
# events   99   98 
Confusional state * 1     
# participants affected / at risk   28/3997 (0.70%)   23/4001 (0.57%) 
# events   28   24 
Depression * 1     
# participants affected / at risk   68/3997 (1.70%)   73/4001 (1.82%) 
# events   68   77 
Insomnia * 1     
# participants affected / at risk   172/3997 (4.30%)   185/4001 (4.62%) 
# events   199   202 
Sleep disorder * 1     
# participants affected / at risk   25/3997 (0.63%)   16/4001 (0.40%) 
# events   25   18 
Renal and urinary disorders     
Dysuria * 1     
# participants affected / at risk   22/3997 (0.55%)   15/4001 (0.37%) 
# events   23   15 
Haematuria * 1     
# participants affected / at risk   65/3997 (1.63%)   48/4001 (1.20%) 
# events   68   53 
Renal cyst * 1     
# participants affected / at risk   65/3997 (1.63%)   61/4001 (1.52%) 
# events   65   63 
Renal failure * 1     
# participants affected / at risk   52/3997 (1.30%)   47/4001 (1.17%) 
# events   55   48 
Renal failure acute * 1     
# participants affected / at risk   25/3997 (0.63%)   19/4001 (0.47%) 
# events   26   19 
Urinary retention * 1     
# participants affected / at risk   22/3997 (0.55%)   17/4001 (0.42%) 
# events   23   19 
Renal impairment * 1     
# participants affected / at risk   39/3997 (0.98%)   29/4001 (0.72%) 
# events   40   31 
Reproductive system and breast disorders     
Benign prostatic hyperplasia * 1     
# participants affected / at risk   44/3997 (1.10%)   20/4001 (0.50%) 
# events   45   20 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease * 1     
# participants affected / at risk   71/3997 (1.78%)   59/4001 (1.47%) 
# events   92   84 
Cough * 1     
# participants affected / at risk   107/3997 (2.68%)   94/4001 (2.35%) 
# events   118   100 
Dyspnoea * 1     
# participants affected / at risk   107/3997 (2.68%)   99/4001 (2.47%) 
# events   120   112 
Epistaxis * 1     
# participants affected / at risk   123/3997 (3.08%)   66/4001 (1.65%) 
# events   145   83 
Haemoptysis * 1     
# participants affected / at risk   37/3997 (0.93%)   32/4001 (0.80%) 
# events   40   37 
Pleural effusion * 1     
# participants affected / at risk   28/3997 (0.70%)   31/4001 (0.77%) 
# events   32   32 
Oropharyngeal pain * 1     
# participants affected / at risk   27/3997 (0.68%)   27/4001 (0.67%) 
# events   28   28 
Skin and subcutaneous tissue disorders     
Decubitus ulcer * 1     
# participants affected / at risk   21/3997 (0.53%)   18/4001 (0.45%) 
# events   22   23 
Ecchymosis * 1     
# participants affected / at risk   42/3997 (1.05%)   39/4001 (0.97%) 
# events   47   42 
Erythema * 1     
# participants affected / at risk   27/3997 (0.68%)   37/4001 (0.92%) 
# events   30   41 
Pruritus * 1     
# participants affected / at risk   47/3997 (1.18%)   50/4001 (1.25%) 
# events   47   51 
Rash * 1     
# participants affected / at risk   41/3997 (1.03%)   50/4001 (1.25%) 
# events   44   51 
Vascular disorders     
Haematoma * 1     
# participants affected / at risk   24/3997 (0.60%)   24/4001 (0.60%) 
# events   29   26 
Hypertension * 1     
# participants affected / at risk   154/3997 (3.85%)   156/4001 (3.90%) 
# events   177   178 
Hypertensive crisis * 1     
# participants affected / at risk   20/3997 (0.50%)   16/4001 (0.40%) 
# events   23   18 
Hypotension * 1     
# participants affected / at risk   82/3997 (2.05%)   93/4001 (2.32%) 
# events   91   102 
Phlebitis * 1     
# participants affected / at risk   37/3997 (0.93%)   38/4001 (0.95%) 
# events   38   41 
Aortic arteriosclerosis * 1     
# participants affected / at risk   25/3997 (0.63%)   19/4001 (0.47%) 
# events   25   19 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (13.1)



  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] .


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