Efficacy and Safety of Dabigatran Compared to Warfarin for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism

This study has been completed.
Sponsor:
Information provided by:
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00291330
First received: February 13, 2006
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Thromboembolism
Drug: dabigatran etexilate 150 mg
Drug: warfarin (INR 2-3)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • Number of Participants With Recurrent Symptomatic Venous Thromboembolism (VTE) and Deaths Related to VTE [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]
    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:
  • Number of Participants With Recurrent Symptomatic VTE and All Deaths [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants With Recurrent Symptomatic DVT [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants With Recurrent Symptomatic Non-fatal PE [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Who Died Due to VTE [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Who Died (Any Cause) [ Time Frame: From randomisation to end of post treatment period (day 224) ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Major Bleeding Events [ Time Frame: From first intake of study drug to last intake of study drug + 6 days ] [ Designated as safety issue: Yes ]

    Major Bleeding Events defined as per the recommendations of the International Society on Thrombosis and Haemostasis. A bleeding event was categorised as an MBE (adjudicated by the independent central assessment committee) if it fulfilled at least one of the following criteria:

    • 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.


Enrollment: 2564
Study Start Date: February 2006
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00291330

  Show 250 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00291330     History of Changes
Other Study ID Numbers: 1160.53, 2005-001999-12
Study First Received: February 13, 2006
Results First Received: November 18, 2010
Last Updated: June 22, 2012
Health Authority: Argentina: A.N.M.A.T. (National Administration of Medications, Food and Medical Technology)
Australia: Responsilble Ethics Committee
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products
Brazil: National Health Surveillance Agency
Canada: Health Canada, Therapeutic Products Directorate
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Denmark: The Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Greece: National Organization for Medicines (EOF) National Ethics Committee
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drug Control General of India
Israel: Clinical trials unit, pharmaceutical division, ministry of health 29 Rivka street Jerusalem
Italy: Comitato Etico Aziende Sanitarie Umbria - ELLERA DI CORCIANO (PG)
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Multicentre Ethics Committee/Medsafe
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Portugal: INFARMED - National Authority of Medicines and Health Products, IP
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
South Africa: Medicines Control Council
Spain: Spanish Agency for Medicines and Health Products
Sweden: The National Board of Health and Welfare
Turkey: Ministry of Health Central Ethics Committee
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)
United States: Food and Drug Administration

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 23, 2013