Secondary Prevention of Venous Thrombo Embolism (VTE). (RE-MEDY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00329238
First received: May 23, 2006
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 administered orally and warfarin (International Normalized Ratio (INR) of 2.0-3.0) for the long-term treatment and secondary prevention of symptomatic venous thromboembolism in patients who have been successfully treated with standard doses of an approved anticoagulant for three to twelve months for confirmed acute symptomatic Venous Thrombo-embolism.

Condition Intervention Phase
Thromboembolism
Drug: Dabigatran
Drug: Warfarin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase III, Randomised, Multicenter, Double-blind, Parallel-group, Active Controlled Study to Evaluate the Efficacy and Safety of Oral Dabigatran Etexilate (150 mg Bid) Compared to Warfarin (INR 2.0-3.0) for the Secondary Prevention of Venous Thromboembolism.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Composite of Recurrent VTE or VTE Death at 36 Months [ Time Frame: 36 months ]
    Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE.

  • Composite of Recurrent VTE or VTE Death at 18 Months [ Time Frame: 18 months ]
    Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and death related to VTE. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation. In case of death, autopsy was an additional way to confirm VTE.


Secondary Outcome Measures:
  • Composite of Recurrent VTE or All Cause Death at 36 Months [ Time Frame: 36 months ]
    Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation.

  • Composite of Recurrent VTE or All Cause Death at 18 Months [ Time Frame: 18 months ]
    Endpoint is a composite of recurrent Venous Thromboembolic Event (VTE) and all cause death. VTE was defined as the composite of symptomatic Deep Vein Thrombosis (DVT) of the leg and Pulmonary embolism (PE). All recurrent VTEs required objective verification by definitive diagnostic evaluation.

  • Deep Vein Thrombosis (DVT) at 36 Months [ Time Frame: 36 months ]
    Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation.

  • DVT at 18 Months [ Time Frame: 18 months ]
    Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation.

  • Symptomatic Pulmonary Embolism (PE) at 36 Months [ Time Frame: 36 months ]
    Symptomatic pulmonary embolism (PE) at 36 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography.

  • Symptomatic Pulmonary Embolism (PE) at 18 Months [ Time Frame: 18 months ]
    Symptomatic pulmonary embolism (PE) at 18 Months (fatal or non-fatal). All suspected PEs required confirmation by one of the following: ventilation-perfusion (V-Q) lung scan, pulmonary angiography, or spiral (helical) Computed tomography.

  • Deaths Related to VTE at 36 Months [ Time Frame: 36 months ]
    Deaths related to VTE (i.e. fatal PE) at 36 Months. Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way.

  • Deaths Related to VTE at 18 Months [ Time Frame: 18 months ]
    Deaths related to VTE (i.e. fatal PE) at 18 Months. All deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death in a treatment-blinded way.

  • Deaths of All Causes at 36 Months [ Time Frame: 36 months ]
    Deaths of all causes at 36 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments.

  • Deaths of All Causes at 18 Months [ Time Frame: 18 months ]
    Deaths of all causes at 18 Months. All components of the primary efficacy endpoint and all deaths were centrally adjudicated by the Independent Central Adjudication Committee for VTE and death without knowledge of any individual treatment assignments.

  • Number of Participants With Bleeding Events [ Time Frame: first intake of study drug until 6 days following last intake of study drug ]

    MBE (major bleeding event) 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.

    Minor bleeding event was any bleeding that did not fulfil any of the criteria for MBEs

    CRBE (clinically relevant bleeding event) if it is a minor bleeding events which fulfilled at least one of the following criteria

    • Spontaneous skin haematoma ≥25 cm2
    • Spontaneous nose bleed >5 min duration
    • Macroscopic haematuria, either spontaneous or, if associated with an intervention, lasting >24 h
    • Spontaneous rectal bleeding
    • Gingival bleeding >5 min
    • Bleeding leading to hospitalisation or requiring surgical treatment
    • Bleeding leading to a transfusion of <2 units of whole blood or red cells
    • Any other bleeding event considered clinically relevant by the investigator

  • Laboratory Analysis [ Time Frame: 18 months + 30 days follow up ]
    Patients with LFT (liver function tests) increases of possible clinical significance during treatment. Increases of possible clinical significance were defined as: ≥3 x ULN (AST, ALT), ≥2 x ULN (AP), and ≥2 mg/dL (total bilirubin). Only patients with a baseline value which was not of possible clinical significance (or without any baseline value) could have a PCSA (Possible clinically significant abnormality).

  • Number of Participants With Definite Acute Coronary Syndrome (ACS) [ Time Frame: day of first study drug intake until last day of study drug intake; from the day after last intake of study drug until trial termination ]
    All suspected ACS occurring during the trial were to be recorded on the CRF and were to be centrally adjudicated by an independent ACS/AC in a treatment-blinded manner.


Enrollment: 2867
Study Start Date: May 2006
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabigatran
Patient to receive 1 capsule containing dabigatran 150 mg twice daily plus placebo tablets for warfarin as decided by sham INR measurements
Drug: Dabigatran
Dabigatran 150 mg BID (twice daily)
Active Comparator: Warfarin (INR of 2.0-3.0)
Patient to receive warfarin tablets to target INR 2.0-3.0 plus placebo capsules for dabigatran twice daily
Drug: Warfarin
Warfarin dosed individually to maintain INR 2.0-3.0

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Inclusion_Criteria

  • Acute symptomatic deep vein thrombosis (DVT)
  • Pulmonary embolism (PE) 3-12 months prior to screening, which has been documented by objective testing

Exclusion criteria:

Exclusion_Criteria

  • Symptomatic DVT or PE at screening Interruption of anticoagulant therapy for 2 or more weeks during the 3-12 months of treatment for the prior VTE.
  • Patients who in the investigators judgement are perceived as having an excessive risk of bleeding Elevated Aspartate aminotransferase (AST) or Alanine tranminase (ALT) > 2x ULN
  • Severe renal impairment (estimated creatinine clearance <= 30 ml/min)
  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: NCT00329238

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00329238     History of Changes
Other Study ID Numbers: 1160.47  2005-002536-94 
Study First Received: May 23, 2006
Results First Received: August 10, 2011
Last Updated: May 8, 2014

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Warfarin
Dabigatran
Anticoagulants
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on January 19, 2017