Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long Term Prevention of Recurrent Symptomatic VTE (RE-SONATE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00558259
First received: November 13, 2007
Last updated: June 17, 2014
Last verified: February 2014
  Purpose

The primary efficacy objective is to evaluate whether dabigatran etexilate is superior to placebo in the long-term prevention of recurrent symptomatic venous thrombo-embolism (VTE) in patients with symptomatic deep-vein thrombosis (DVT) or pulmonary embolism (PE) who completed 6 to 18 months of treatment with vitamin K antagonist (VKA).


Condition Intervention Phase
Venous Thromboembolism
Drug: dabigatran etexilate 150 mg twice daily (BID)
Drug: matching placebo twice daily (BID)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Twice-daily Oral Direct Thrombin Inhibitor Dabigatran Etexilate in the Long-term Prevention of Recurrent Symptomatic Proximal Venous Thromboembolism in Patients With Symptomatic Deep-vein Thrombosis or Pulmonary Embolism.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Including Unexplained Death During the Intended Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Symptomatic recurrent VTE is the composite of recurrent deep vein thrombosis (DVT) , fatal or non-fatal pulmonary embolism (PE). Whilst the endpoint is time to event, the measured values present the number of participant with event and the hazard ratio presents the time to event.


Secondary Outcome Measures:
  • Centrally Confirmed Symptomatic Recurrent Venous Thrombotic Events (VTE) Excluding Unexplained Death During the Intended Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Symptomatic recurrent VTE is the composite of recurrent deep vein thrombosis (DVT) , fatal or non-fatal pulmonary embolism (PE). Whilst the endpoint is time to event, the measured values present the number of participant with event and the hazard ratio presents the time to event.

  • Centrally Confirmed Symptomatic Recurrent Deep Venous Thrombotic (DVT) Events During the Intended Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of the participants with centrally confirmed symptomatic recurrent deep venous thrombotic (DVT) events during the intended treatment period were described.

  • Centrally Confirmed Symptomatic Pulmonary Embolism (PE) Events During the Intended Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of participants with centrally confirmed symptomatic pulmonary embolism (PE) events during the intended treatment period were described.

  • Centrally Confirmed Unexplained Deaths During the Intended Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of participants with centrally confirmed unexplained deaths during the intended treatment period were described.

  • Centrally Confirmed Bleeding Event During the Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

    Major bleeding events (MBE) had to fulfil at least 1 of the following criteria:

    • Fatal bleeding
    • Associated with a fall in haemoglobin of ≥2 g/dL
    • Led to the transfusion of ≥2 units packed cells or whole blood
    • Occurred in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal

    Other clinically relevant bleeding was defined as overt bleeding not meeting the criteria for an MBE but associated with medical intervention, unscheduled contact with a physician, (temporary) cessation of study treatment, or associated with discomfort such as pain, or impairment of activities of daily life.

    Examples of these bleedings were:

    • Bleeding that compromised haemodynamics
    • Bleeding that led to hospitalisation

    Trivial bleeding events were defined as all other bleeding events that did not fulfil the criteria of MBEs or CRBEs.

    All bleeding events include MBEs, CRBEs, and trivial bleeding events.


  • Centrally Confirmed Cardiovascular Events During the Treatment Period [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Cardiovascular events that occurred during the treatment period + 3 days were summarised by treatment groups.

  • Laboratory Measures, Especially Liver Function Tests (LFTs) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number of participants with possible clinically significant abnormalities during the treatment period.


Enrollment: 1353
Study Start Date: November 2007
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dabigatran etexilate 150 mg BID
Patient to receive dabigatran etexilatate capsules 150 mg twice daily
Drug: dabigatran etexilate 150 mg twice daily (BID)
dabigatran etexilate capsules 150 mg BID
Placebo Comparator: matching placebo twice daily (BID)
Patient to receive dabigatran extexilate matching placebo capsules twice daily
Drug: matching placebo twice daily (BID)
Matching placebo BID

  Eligibility

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

Inclusion criteria:

  1. Patients with confirmed symptomatic PE or proximal DVT of the leg(s) who have been treated for 6 to 18 months with therapeutic dosages (intended INR between 2-3) of an oral VKA (e.g. warfarin, acenocoumarol, phenprocoumon, or fluindione) or RE-COVER study medication up to the moment of screening for the current study.
  2. Written informed consent

Exclusion criteria:

  1. Younger then 18 years of age
  2. Indication for VKA other than DVT and/or PE
  3. Patients in whom anticoagulant treatment for their index PE or DVT should be continued
  4. Active liver disease or liver disease decreasing survival (e.g. acute hepatitis, chronic active hepatitis, cirrhosis) or ALAT > 3 x ULN
  5. Creatinine clearance < 30 ml/min
  6. Acute bacterial endocarditis
  7. Active bleeding or high risk for bleeding.
  8. Uncontrolled hypertension (investigators judgement)
  9. Intake of another experimental drug within the 30 days prior to randomization into the study
  10. Life expectancy <6 months
  11. Childbearing potential without proper contraceptive measures*, pregnancy or breast feeding
  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: NCT00558259

  Show 147 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: NCT00558259     History of Changes
Other Study ID Numbers: 1160.63, 2007-002586-12
Study First Received: November 13, 2007
Results First Received: January 31, 2012
Last Updated: June 17, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Canada: Health Canada
Czech Republic: State Institute for Drug Control (SUKL), CZ-100 41 Prague 10
Estonia: State Agency of Medicines, EE-5041Tartu
Germany: BfArM-Federal Authorities for Drugs and Medical Devices
Italy: Comitato di Bioetica dell'Azienda Ospedaliero-Universitaria Policlinico "Giaccone" di Palermo
Korea, Republic of: Korea Drug and Food Administration
Latvia: State Agency of Medicines, LV-1003 Riga
Lithuania: State Medicines Control Agency, LT-01132 Vilnius
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
New Zealand: Multicentre Ethics Committee/Medsafe
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Pharmacological Committee, Ministry of Health
Singapore: Health Sciences Authority,Ministry of Health
South Africa: Medicines Control Council
Sweden: Medical Products Agency Regional Ethics Committee of Gothenburg
Switzerland: Swissmedic Schweizerisches Heilmittelinstitut (Swiss Agency for Therapeutic Products
Thailand: Ministry of Public Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Antithrombins
Antithrombin Proteins
Dabigatran
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 September 30, 2014