Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE (RE-SONATE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00558259
First received: November 13, 2007
Last updated: February 24, 2014
Last verified: February 2014
Results First Received: January 31, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double-Blind;   Primary Purpose: Prevention
Condition: Venous Thromboembolism
Interventions: Drug: dabigatran etexilate 150 mg twice daily (BID)
Drug: matching placebo twice daily (BID)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
There were 3 patients randomised to placebo who received Dabigatran only. For all analyses of efficacy, these patients are analysed as randomised. For all analyses of safety, these patients are analysed as treated.

Reporting Groups
  Description
Dabigatran Dabigatran 150mg bid (twice daily)
Placebo Matching placebo

Participant Flow:   Overall Study
    Dabigatran     Placebo  
STARTED     681 [1]   662 [2]
COMPLETED     610 [3]   563 [3]
NOT COMPLETED     71     99  
Adverse Event                 50                 81  
Protocol Violation                 9                 5  
Withdrawal by Subject                 12                 13  
[1] Number who started treatment. There were 4 patients randomised to Dabigatran and not treated.
[2] Number who started treatment. There were 6 patients randomised to placebo and not treated.
[3] Completed treatment.



  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
Dabigatran Dabigatran 150mg bid
Placebo Matching placebo
Total Total of all reporting groups

Baseline Measures
    Dabigatran     Placebo     Total  
Number of Participants  
[units: participants]
  681     662     1343  
Age  
[units: Years]
Mean ± Standard Deviation
  56.1  ± 15.5     55.5  ± 15.1     55.8  ± 15.3  
Gender  
[units: Participants]
     
Female     300     298     598  
Male     381     364     745  
Body mass index (BMI) continuous  
[units: kg/m^2]
Mean ± Standard Deviation
  28.45  ± 5.44     28.41  ± 5.56     28.43  ± 5.50  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Including Unexplained Death During the Intended Treatment Period   [ Time Frame: 6 months ]

2.  Secondary:   Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Excluding Unexplained Death During the Intended Treatment Period   [ Time Frame: 6 months ]

3.  Secondary:   Centrally Confirmed Symptomatic Recurrent Deep Venous Thrombotic (DVT) Events During the Intended Treatment Period   [ Time Frame: 6 months ]

4.  Secondary:   Centrally Confirmed Symptomatic Pulmonary Embolism (PE) Events During the Intended Treatment Period   [ Time Frame: 6 months ]

5.  Secondary:   Centrally Confirmed Unexplained Deaths During the Intended Treatment Period   [ Time Frame: 6 months ]

6.  Secondary:   Centrally Confirmed Bleeding Event During the Treatment Period   [ Time Frame: 6 months ]

7.  Secondary:   Centrally Confirmed Cardiovascular Events During the Treatment Period   [ Time Frame: 6 months ]

8.  Secondary:   Laboratory Measures, Especially Liver Function Tests (LFTs)   [ Time Frame: 6 months ]


  Serious Adverse Events
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Time Frame 6 months
Additional Description There were 3 patients who were randomised to placebo but who were treated with dabigatran only.

Reporting Groups
  Description
Dabigatran Dabigatran 150mg bid
Placebo Matching placebo

Serious Adverse Events
    Dabigatran     Placebo  
Total, serious adverse events      
# participants affected / at risk     47/684 (6.87%)     60/659 (9.10%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Splenomegaly † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Cardiac disorders      
Acute myocardial infarction † 1    
# participants affected / at risk     1/684 (0.15%)     1/659 (0.15%)  
Angina pectoris † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Atrial fibrillation † 1    
# participants affected / at risk     0/684 (0.00%)     2/659 (0.30%)  
Cardiac failure † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Hypertensive heart disease † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Ear and labyrinth disorders      
Vertigo † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Eye disorders      
Amaurosis fugax † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Optic ischaemic neuropathy † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Gastrointestinal disorders      
Abdominal pain † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Abdominal pain upper † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Colitis † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Colonic polyp † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Enteritis † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Gastric ulcer † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Gastric ulcer haemorrhage † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Gastritis † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Haematemesis † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Inguinal hernia † 1    
# participants affected / at risk     0/684 (0.00%)     2/659 (0.30%)  
Nausea † 1    
# participants affected / at risk     1/684 (0.15%)     1/659 (0.15%)  
Rectal haemorrhage † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Vomiting † 1    
# participants affected / at risk     1/684 (0.15%)     1/659 (0.15%)  
General disorders      
Chest pain † 1    
# participants affected / at risk     2/684 (0.29%)     1/659 (0.15%)  
Oedema † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Pain † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Polyp † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Pyrexia † 1    
# participants affected / at risk     0/684 (0.00%)     2/659 (0.30%)  
Unevaluable event † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Hepatobiliary disorders      
Cholestasis † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Infections and infestations      
Abscess limb † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Anal abscess † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Arthritis infective † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Lobar pneumonia † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Pneumonia † 1    
# participants affected / at risk     2/684 (0.29%)     2/659 (0.30%)  
Salmonella bacteraemia † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Salmonellosis † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Urinary tract infection † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Injury, poisoning and procedural complications      
Fall † 1    
# participants affected / at risk     1/684 (0.15%)     2/659 (0.30%)  
Femur fracture † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Head injury † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Joint injury † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Post procedural haemorrhage † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Radius fracture † 1    
# participants affected / at risk     2/684 (0.29%)     0/659 (0.00%)  
Rib fracture † 1    
# participants affected / at risk     0/684 (0.00%)     3/659 (0.46%)  
Scapula fracture † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Skin laceration † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Thermal burn † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Musculoskeletal and connective tissue disorders      
Arthralgia † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Arthrofibrosis † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Back pain † 1    
# participants affected / at risk     2/684 (0.29%)     0/659 (0.00%)  
Intervertebral disc protrusion † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Musculoskeletal pain † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Osteoarthritis † 1    
# participants affected / at risk     2/684 (0.29%)     0/659 (0.00%)  
Rheumatoid arthritis † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Adenocarcinoma pancreas † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Breast neoplasm † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Chronic lymphocytic leukaemia † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Colon cancer † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Gastric cancer † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Lung adenocarcinoma † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Lung neoplasm † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Metastases to bladder † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Ovarian neoplasm † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Prostate cancer † 1    
# participants affected / at risk     1/684 (0.15%)     1/659 (0.15%)  
Rectal cancer stage I † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Squamous cell carcinoma † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Nervous system disorders      
Chronic inflammatory demyelinating polyradiculoneuropathy † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Diabetic hyperglycaemic coma † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Hydrocephalus † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Ischaemic stroke † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Nerve compression † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Psychiatric disorders      
Personality disorder † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Reproductive system and breast disorders      
Metrorrhagia † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Respiratory, thoracic and mediastinal disorders      
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     2/684 (0.29%)     4/659 (0.61%)  
Dyspnoea † 1    
# participants affected / at risk     1/684 (0.15%)     2/659 (0.30%)  
Lung disorder † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Pleural effusion † 1    
# participants affected / at risk     2/684 (0.29%)     0/659 (0.00%)  
Pneumothorax † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Pulmonary artery thrombosis † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Pulmonary embolism † 1    
# participants affected / at risk     1/684 (0.15%)     16/659 (2.43%)  
Pulmonary hypertension † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Pulmonary infarction † 1    
# participants affected / at risk     0/684 (0.00%)     2/659 (0.30%)  
Surgical and medical procedures      
Abdominal wall operation † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Vascular disorders      
Deep vein thrombosis † 1    
# participants affected / at risk     2/684 (0.29%)     15/659 (2.28%)  
Embolism venous † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Essential hypertension † 1    
# participants affected / at risk     1/684 (0.15%)     0/659 (0.00%)  
Haematoma † 1    
# participants affected / at risk     0/684 (0.00%)     1/659 (0.15%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.1




  Other Adverse Events


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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 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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
No text entered.  


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided by Boehringer Ingelheim

Publications automatically indexed to this study:

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00558259     History of Changes
Other Study ID Numbers: 1160.63, 2007-002586-12
Study First Received: November 13, 2007
Results First Received: January 31, 2012
Last Updated: February 24, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Estonia: State Agency of Medicines, EE-5041Tartu
Germany: BfArM-Federal Authorities for Drugs and Medical Devices
Italy: Comitato di Bioetica dell'Azienda Ospedaliero-Universitaria Policlinico "Giaccone" di Palermo
Korea, Republic of: Korea Drug and Food Administration
Latvia: State Agency of Medicines, LV-1003 Riga
Lithuania: State Medicines Control Agency, LT-01132 Vilnius
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Multicentre Ethics Committee/Medsafe
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority,Ministry of Health
South Africa: Medicines Control Council
Sweden: Medical Products Agency Regional Ethics Committee of Gothenburg
Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products
Thailand: Ministry of Public Health
United States: Food and Drug Administration