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: December 10, 2013
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
Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Symptomatic Deep vein thrombosis (DVT). All DVT events required objective verification through definitive diagnostic evaluation.

  • DVT at 18 Months [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00329238

  Show 275 Study Locations
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: 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: December 10, 2013
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Bundesamt für Sicherheit im Gesundheitswesen, A-1030 Vienna
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
Canada: Health Canada, Therapeutic Products Directorate
China: Ministry of Health
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Denmark: The Danish Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: BfArM-Federal Authorities for Drugs and Medical Devices
Great Britain: MHRA
Greece: National Organization for Medicines (EOF) National Ethics Committee
Hungary: National Institute of Pharmacy, H-1051 Budapest
India: Drug Control General of India
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Comitato Etico delle Aziende Sanitarie dell'Umbria di Perugia
Mexico: Comisión Federal para la Protección contra Riesgos Sanitarios COFEPRIS Federal Commission for Protection against Sanitary Hazards
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Multicentre Ethics Committee/Medsafe
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Poland: Registration Medicinal Product Medical Device Biocidal Product
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
South Africa: Medicines Control Council
Spain: Spanish Agency for Medicines and Health Products
Sweden: Medical Products Agency Regional Ethical Review Board
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
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014