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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)

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ClinicalTrials.gov Identifier: NCT00680186
Recruitment Status : Completed
First Posted : May 20, 2008
Results First Posted : June 14, 2012
Last Update Posted : May 19, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE May 16, 2008
First Posted Date  ICMJE May 20, 2008
Results First Submitted Date  ICMJE May 4, 2012
Results First Posted Date  ICMJE June 14, 2012
Last Update Posted Date May 19, 2014
Study Start Date  ICMJE April 2008
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 19, 2008)
A composite of recurrent symptomatic VTE and deaths related to VTE within 6 months (VTE is defined as the composite incidence of DVT of the leg (including the inferior caval vein) and PE).
Change History Complete list of historical versions of study NCT00680186 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2013)
  • 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 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. ]
    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. ]
    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) ]
    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. ]
    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. ]
    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 ]
    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 ]
    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 ]
    Frequency of patients with possible clinically significant abnormalities.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 19, 2008)
Efficacy: Composite of recurrent symptomatic VTE and all deaths, Symptomatic DVT, Symptomatic PE, Deaths related to VTE, All deaths Safety: Incidence of Bleeding Events, AE, Discontinuation due to AE, Laboratory measures, ACS, vital signs.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)
Official Title  ICMJE 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
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Thromboembolism
Intervention  ICMJE
  • Drug: Warfarin
    PRN (to maintain a target INR of 2.0-3.0)
  • Drug: Dabigatran etexilate
    150mg bid
Study Arms  ICMJE
  • Experimental: Dabigatran etexilate (150mg bid)
    Patients will receive 1 capsule containing 150 mg dabigatran etexilate/matching placebo twice daily
    Intervention: Drug: Dabigatran etexilate
  • 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
    Intervention: Drug: Warfarin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 1, 2011)
2589
Original Enrollment  ICMJE
 (submitted: May 19, 2008)
2554
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Brazil,   Bulgaria,   Canada,   China,   Czech Republic,   Denmark,   France,   Hungary,   India,   Israel,   Italy,   Korea, Republic of,   Malaysia,   Netherlands,   New Zealand,   Norway,   Philippines,   Poland,   Russian Federation,   Singapore,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00680186
Other Study ID Numbers  ICMJE 1160.46
2007-002631-86 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP