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

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.”

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.

Intervention(s) in this Clinical Trial

• Drug: dabigatran etexilate 150 mg
  • twice daily
• Drug: warfarin (INR 2-3)
  • prn to maintain INR (2-3)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: dabigatran etexilate 150 mg
  • twice daily
• Active Comparator: warfarin (INR 2-3)
  • prn to maintain INR (2-3)

Primary 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)
    Safety Issue?: No

Secondary Measures

• Number of Participants With Recurrent Symptomatic VTE and All Deaths
  • Time Frame: From randomisation to end of post treatment period (day 224)
    Safety Issue?: No
• Number of Participants With Recurrent Symptomatic DVT
  • Time Frame: From randomisation to end of post treatment period (day 224)
    Safety Issue?: No
• Number of Participants With Recurrent Symptomatic Non-fatal PE
  • Time Frame: From randomisation to end of post treatment period (day 224)
    Safety Issue?: No
• Number of Participants Who Died Due to VTE
  • Time Frame: From randomisation to end of post treatment period (day 224)
    Safety Issue?: No
• Number of Participants Who Died (Any Cause)
  • Time Frame: From randomisation to end of post treatment period (day 224)
    Safety Issue?: No
• Number of Participants With Major Bleeding Events
  • Time Frame: From first intake of study drug to last intake of study drug + 6 days
    Safety Issue?: Yes

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Boehringer Ingelheim Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Boehringer Ingelheim Study Chair Boehringer Ingelheim Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00291330

Study ID Number: 1160.53

ClinicalTrials.gov Identifier: NCT00291330

Health Authority: Argentina: A.N.M.A.T. (National Administration of Medications, Food and Medical Technology)