We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism (RE-COVER I)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00291330
Recruitment Status : Completed
First Posted : February 14, 2006
Results First Posted : February 11, 2011
Last Update Posted : June 6, 2014
Sponsor:
Information provided by:
Boehringer Ingelheim

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this trial is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin as needed (pro re nata - prn) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic venous thromboembolism (VTE), following initial treatment (5-10 days) with a parenteral anticoagulant approved for this indication. This trial aims to demonstrate non-inferiority of dabigatran compared with warfarin in patients with acute symptomatic VTE. After achieving non-inferiority, this trial also aims to establish superiority (by means of hierarchical tests) of dabigatran over warfarin.

Condition or disease Intervention/treatment Phase
Thromboembolism Drug: dabigatran etexilate 150 mg Drug: warfarin (INR 2-3) Phase 3

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2564 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Double Blind, Parallel-group Study of the Efficacy and Safety of Oral Dabigatran Etexilate 150 mg Twice Daily Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism (VTE), Following Initial Treatment (5-10 Days) With a Parenteral Anticoagulant Approved for This Indication.
Study Start Date : February 2006
Actual Primary Completion Date : May 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: dabigatran etexilate 150 mg
twice daily
 Drug: dabigatran etexilate 150 mg
twice daily
Active Comparator: warfarin (INR 2-3)
prn to maintain INR (2-3)
 Drug: warfarin (INR 2-3)
prn to maintain INR (2-3)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE [ Time Frame: For statistical analysis 1: from randomisation to end of post treatment period (ptp), planned to be up to day 224. For statistical analysis 2: from randomisation to 6 months (up to day 180) ]
    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


Secondary Outcome Measures :
  1. Number of Participants With Recurrent Symptomatic VTE and All Deaths [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ]

    VTE or any death which occured from randomisation to end of post treatment period.

    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


  2. Number of Participants With Recurrent Symptomatic DVT [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ]

    Symptomatic DVT which occured from randomisation to end of post treatment period.

    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


  3. Number of Participants With Recurrent Symptomatic Non-fatal PE [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ]

    Symptomatic non-fatal PE which occured from randomisation to end of post treatment period.

    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


  4. Number of Participants Who Died Due to VTE [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ]

    VTE - related deaths which occured from randomisation to end of post treatment period.

    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


  5. Number of Participants Who Died (Any Cause) [ Time Frame: For statistical analysis 1: from randomisation to 6 months (up to day 180) For statistical analysis 2: from randomisation to end of ptp, planned to be up to day 224. ]
    Any deaths which occured from randomisation to end of post treatment period. All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.

  6. Number of Participants With Bleeding Events [ Time Frame: From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) ]

    Major bleeding events (MBE) were defined as

    • Fatal bleeding
    • Symptomatic bleeding in a critical area or organ
    • Bleeding causing a fall in haemoglobin level of 20 g/L (1.24 mmol/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells

    Clinically-relevant bleeding events (CRBE) was defined as

    • spontaneous skin hematoma >=25 cm²
    • spontaneous nose bleed >5 min
    • macroscopic hematuria spontaneous or >24 hours if associated with an intervention
    • spontaneous rectal bleeding (more than spotting on toilet paper)
    • gingival bleeding >5 min
    • leading to hospitalisation and / or requiring surgical treatment
    • leading to a transfusion of <2 units of whole blood or red cells
    • any other bleeding event considered clinically relevant by the investigator

    Any bleeding events were defined as major, clinically-relevant and nuisance bleeding events. Nuisance bleeding events were defined as all other bleeding events that did not fulfil the criteria from above.


  7. Number of Participants With Acute Coronary Syndrome (ACS) [ Time Frame: From first intake of study drug to end of study conduct ]

    Any ACS occurring during the conduct of the study (centrally adjudicated as definite).

    Counts of patients having a centrally adjudicated definite ACS during intake of active study drug, after stopping active study drug and before or without intake of active study drug, according to treatment group.

    All suspected recurrent VTEs and all deaths and bleeding events were evaluated by an independent central adjudication committee, and all analyses are based on the events that were centrally confirmed by this committee.


  8. Laboratory Analyses [ Time Frame: From first intake of study drug to last intake of study drug + 6 days washout (washout time can be reduced until 0 day if the patient takes an other anti-coagulant therapy on and after last intake of active study drug) ]
    Frequency of patients with possible clinically significant abnormalities.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Acute deep vein thrombosis (DVT) of the leg involving proximal veins, and/or pulmonary embolism (PE) iin patients for whom at least 6 months of anticoagulant therapy is considered appropriate
  2. Male or female, being 18 years of age or older
  3. Written informed consent for study participation

Exclusion criteria

  1. Overt symptoms of VTE for longer than 2 weeks prior to enrolment
  2. PE satisfying at least one of the following criteria: Haemodynamic instability, embolectomy is indicated or performed, thrombolytic therapy is indicated or performed, or suspected source of PE is other than the legs
  3. Actual or anticipated use of vena cava filter
  4. Contraindications to anticoagulant therapy
  5. Patients who in the investigators opinion should not be treated with warfarin
  6. Allergy to heparins or other alternate approved therapy used for initial treatment, warfarin or dabigatran, or to one of the excipients included in these medications
  7. Patients who in the investigators judgement are perceived as having an excessive risk of bleeding
  8. Known anaemia
  9. Need of anticoagulant treatment for disorders other than VTE
  10. Recent unstable cardiovascular disease
  11. Elevated AST or ALT > 2x ULN
  12. Liver disease expected to have any potential impact on survival
  13. Patients who have developed transaminase elevations upon exposure to ximelagatran
  14. Severe renal impairment
  15. Women who are pregnant, nursing, or of childbearing potential who refuse to use a medically acceptable form of contraception
  16. Participation in another clinical trial with an investigational drug during the last 30 days or previous participation in this study
  17. Patients considered unsuitable for inclusion by the investigator
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00291330


Locations
Show Show 250 study locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Layout table for investigator information
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00291330    
Other Study ID Numbers: 1160.53
2005-001999-12 ( EudraCT Number: EudraCT )
First Posted: February 14, 2006    Key Record Dates
Results First Posted: February 11, 2011
Last Update Posted: June 6, 2014
Last Verified: April 2014
Additional relevant MeSH terms:
Layout table for MeSH terms
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Warfarin
Dabigatran
 Anticoagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action