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Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE) (RE-COVER II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00680186
First received: May 16, 2008
Last updated: May 8, 2014
Last verified: December 2013
  Purpose

The general aim of this study is to determine the comparative safety and efficacy of dabigatran etexilate 150 mg bid administered orally and warfarin Pro re nata (As needed/PRN) to maintain an International Normalised Ratio (INR) of 2.0-3.0 for 6 month treatment of acute symptomatic VTE.

The primary objective is to investigate the efficacy of dabigatran compared to warfarin during the 6 month treatment period. The investigation of other selected efficacy aspects and safety are regarded as secondary objective of this trial.


Condition Intervention Phase
Thromboembolism
Drug: Warfarin
Drug: Dabigatran etexilate
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 Bid) Compared to Warfarin (INR 2.0-3.0) for 6 Month Treatment of Acute Symptomatic Venous Thromboembolism, 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:

Primary Outcome Measures:
  • 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) ] [ 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: 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. ] [ Designated as safety issue: No ]
    VTE or any death which occured from randomisation to end of ptp. 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: 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. ] [ Designated as safety issue: No ]
    Symptomatic DVT which occured from randomisation to end of ptp. 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: 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. ] [ Designated as safety issue: No ]
    Symptomatic non-fatal PE which occured from randomisation to end of ptp. 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 6 months (up to day 180) and to end of ptp (planned to be up to day 224) ] [ Designated as safety issue: No ]
    VTE - related deaths which occured from randomisation to end of ptp. 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. Hazard ratios and 95% CI were not calculated because of insufficient number of events.

  • 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. ] [ Designated as safety issue: No ]
    Any deaths which occured from randomisation to end of ptp. 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 Fatal and 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. ] [ Designated as safety issue: No ]
    Symptomatic fatal and non-fatal PE which occured from randomisation to end of ptp. 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 MBE, MBE and/or CRBE, and Any Bleeding Events [ Time Frame: From first intake of study drug to last intake of study drug + 6 days washout ] [ Designated as safety issue: Yes ]

    Major bleeding events (MBE) are 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) are defined as

    • spontaneous skin hematoma >=25 cm²
    • wound hematoma >=100 cm²
    • spontaneous nose bleed >5 min
    • macroscopic hematuria spontaneous or >24 hours if associated with an intervention
    • spontaneous rectal bleeding
    • 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.


  • Number of Participants With Acute Coronary Syndrome (ACS) [ Time Frame: From first intake of study drug to last contact date ] [ Designated as safety issue: No ]
    Any ACS occurring during the conduct of the study (centrally adjudicated as definite). Patients having a centrally adjudicated definite ACS during intake of study drug and after stopping study drug, according to treatment group. ACS assessments pre-specified in the protocol without adjudication. Prior to database lock, the steering committee asked to have ACS events adjudicated by an independent committee. After database lock, the committee was provided with source documentation that was blinded to the patient's treatment assignment. ACS results presented are based on adjudication findings.

  • Laboratory Analyses [ Time Frame: From first intake of study drug to last intake of study drug + 6 days washout ] [ Designated as safety issue: No ]
    Frequency of patients with possible clinically significant abnormalities.


Enrollment: 2589
Study Start Date: April 2008
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran etexilate (150mg bid)
Patients will receive 1 capsule containing 150 mg dabigatran etexilate/matching placebo twice daily
Drug: Dabigatran etexilate
150mg bid
Active Comparator: Warfarin (INR 2.0-3.0)
Patients will receive tablets PRN warfarin/matching placebo to maintain a target INR of 2.0-3.0
Drug: Warfarin
PRN (to maintain a target INR of 2.0-3.0)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Acute symptomatic uni- or bilateral Deep Vein Thrombosis (DVT) of the leg involving proximal veins, and/or Pulmonary Embolism (PE)
  • Male or female, being 18 years of age or older
  • Written informed consent for study participation

Exclusion criteria:

  • Persistent symptoms of VTE
  • PE requiring urgent intervention
  • Use of vena cava filter
  • Contraindications to anticoagulant therapy
  • Allergy to study medications
  • Elevated Aspartate-aminotransferase (AST) or Alanine-aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) or known liver disease expected to have an impact on survival
  • Severe renal impairment
  • Patients considered unsuitable for inclusion
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00680186

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Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00680186     History of Changes
Other Study ID Numbers: 1160.46, 2007-002631-86
Study First Received: May 16, 2008
Results First Received: May 4, 2012
Last Updated: May 8, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
Canada: Health Canada, Therapeutic Products Directorate
China: Food and Drug Administration
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Denmark: Danish Medicines Agency
France: AFSSAPS
Great Britain: MHRA
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drugs Controller General of India
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Korea, Republic of: Korea Drug and Food Administration
Malaysia: National Pharmaceutical Control Bureau
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Multicentre Ethics Committee/Medsafe
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Philippines: Department of Health
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Singapore: Health Sciences Authority,Ministry of Health
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
South Africa: MCC (Medicines Control Council)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Sweden: Medical Products Agency
Taiwan: Department of Health
Thailand: Ministry of Public Health
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
Dabigatran
Warfarin
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014