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: December 10, 2013
Last verified: December 2013

May 16, 2008
December 10, 2013
April 2008
May 2011   (final data collection date for primary outcome measure)
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.
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).
Complete list of historical versions of study NCT00680186 on ClinicalTrials.gov Archive Site
  • 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.
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.
Not Provided
Not Provided
 
Phase III Study Testing Efficacy & Safety of Oral Dabigatran Etexilate vs Warfarin for 6 m Treatment for Acute Symp Venous Thromboembolism (VTE)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Thromboembolism
  • Drug: Warfarin
    PRN (to maintain a target INR of 2.0-3.0)
  • Drug: Dabigatran etexilate
    150mg bid
  • 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
Majeed A, Hwang HG, Connolly SJ, Eikelboom JW, Ezekowitz MD, Wallentin L, Brueckmann M, Fraessdorf M, Yusuf S, Schulman S. Management and outcomes of major bleeding during treatment with dabigatran or warfarin. Circulation. 2013 Nov 19;128(21):2325-32. doi: 10.1161/CIRCULATIONAHA.113.002332. Epub 2013 Sep 30.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
2589
Not Provided
May 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   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
 
NCT00680186
1160.46, 2007-002631-86
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
December 2013

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