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

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Locations
United States, Alabama
1160.63.01025 Boehringer Ingelheim Investigational Site
Birmingham, Alabama, United States
1160.63.01023 Boehringer Ingelheim Investigational Site
Huntsville, Alabama, United States
United States, California
1160.63.01002 Boehringer Ingelheim Investigational Site
Laguna Hills, California, United States
United States, Colorado
1160.63.01014 Boehringer Ingelheim Investigational Site
Colorado Springs, Colorado, United States
United States, Florida
1160.63.01003 Boehringer Ingelheim Investigational Site
Jacksonville, Florida, United States
1160.63.01030 Boehringer Ingelheim Investigational Site
Key West, Florida, United States
United States, Louisiana
1160.63.01022 Boehringer Ingelheim Investigational Site
Lafayette, Louisiana, United States
1160.63.01044 Boehringer Ingelheim Investigational Site
New Iberia, Louisiana, United States
United States, Maine
1160.63.01017 Boehringer Ingelheim Investigational Site
Biddeford, Maine, United States
United States, Maryland
1160.63.01004 Boehringer Ingelheim Investigational Site
Salisbury, Maryland, United States
United States, Massachusetts
1160.63.01016 Boehringer Ingelheim Investigational Site
Worcester, Massachusetts, United States
United States, Missouri
1160.63.01037 Boehringer Ingelheim Investigational Site
St. Louis, Missouri, United States
United States, Montana
1160.63.01019 Boehringer Ingelheim Investigational Site
Missoula, Montana, United States
United States, Ohio
1160.63.01032 Boehringer Ingelheim Investigational Site
Columbus, Ohio, United States
United States, Pennsylvania
1160.63.01024 Boehringer Ingelheim Investigational Site
Uniontown, Pennsylvania, United States
1160.63.01001 Boehringer Ingelheim Investigational Site
Uniontown, Pennsylvania, United States
United States, South Carolina
1160.63.01005 Boehringer Ingelheim Investigational Site
Charleston, South Carolina, United States
1160.63.01020 Boehringer Ingelheim Investigational Site
Spartanburg, South Carolina, United States
United States, Utah
1160.63.01011 Boehringer Ingelheim Investigational Site
Salt Lake City, Utah, United States
United States, Virginia
1160.63.01007 Boehringer Ingelheim Investigational Site
Richmond, Virginia, United States
United States, Washington
1160.63.01035 Boehringer Ingelheim Investigational Site
Bellevue, Washington, United States
Australia, Queensland
1160.63.61002 Boehringer Ingelheim Investigational Site
Greenslopes, Queensland, Australia
Australia, South Australia
1160.63.61003 Boehringer Ingelheim Investigational Site
Elizabeth Vale, South Australia, Australia
Australia, Victoria
1160.63.61001 Boehringer Ingelheim Investigational Site
Clayton, Victoria, Australia
Australia, Western Australia
1160.63.61004 Boehringer Ingelheim Investigational Site
Nedlands, Western Australia, Australia
Austria
1160.63.43005 Boehringer Ingelheim Investigational Site
Graz, Austria
1160.63.43006 Boehringer Ingelheim Investigational Site
Innsbruck, Austria
1160.63.43004 Boehringer Ingelheim Investigational Site
Wien, Austria
1160.63.43002 Boehringer Ingelheim Investigational Site
Wien, Austria
1160.63.43001 Boehringer Ingelheim Investigational Site
Wien, Austria
Belgium
1160.63.32005 Boehringer Ingelheim Investigational Site
Aalst, Belgium
1160.63.32004 Boehringer Ingelheim Investigational Site
Duffel, Belgium
1160.63.32003 Boehringer Ingelheim Investigational Site
Kortrijk, Belgium
1160.63.32001 Boehringer Ingelheim Investigational Site
Leuven, Belgium
1160.63.32002 Boehringer Ingelheim Investigational Site
Lier, Belgium
Canada, Alberta
1160.63.02013 Boehringer Ingelheim Investigational Site
Edmonton, Alberta, Canada
Canada, New Brunswick
1160.63.02004 Boehringer Ingelheim Investigational Site
Saint John, New Brunswick, Canada
Canada, Ontario
1160.63.02005 Boehringer Ingelheim Investigational Site
Hamilton, Ontario, Canada
Canada
1160.63.02020 Boehringer Ingelheim Investigational Site
Quebec, Canada
Czech Republic
1160.63.42004 Boehringer Ingelheim Investigational Site
Ceske Budejovice, Czech Republic
1160.63.42003 Boehringer Ingelheim Investigational Site
Jablonec nad Nisou, Czech Republic
1160.63.42008 Boehringer Ingelheim Investigational Site
Kladno, Czech Republic
1160.63.42012 Boehringer Ingelheim Investigational Site
Liberec, Czech Republic
1160.63.42010 Boehringer Ingelheim Investigational Site
Nymburk, Czech Republic
1160.63.42009 Boehringer Ingelheim Investigational Site
Ostrava, Czech Republic
1160.63.42011 Boehringer Ingelheim Investigational Site
Ostrava-Vitkovice, Czech Republic
1160.63.42001 Boehringer Ingelheim Investigational Site
Prague 4, Czech Republic
1160.63.42002 Boehringer Ingelheim Investigational Site
Prague 4-Krc, Czech Republic
1160.63.42006 Boehringer Ingelheim Investigational Site
Praha 4, Czech Republic
1160.63.42005 Boehringer Ingelheim Investigational Site
Prostejov, Czech Republic
1160.63.42007 Boehringer Ingelheim Investigational Site
Rakovnik, Czech Republic
1160.63.42013 Boehringer Ingelheim Investigational Site
Slany, Czech Republic
1160.63.42014 Boehringer Ingelheim Investigational Site
Tabor, Czech Republic
Estonia
1160.63.37202 Boehringer Ingelheim Investigational Site
Kohtla-Järve, Estonia
1160.63.37203 Boehringer Ingelheim Investigational Site
Tallin, Estonia
1160.63.37201 Boehringer Ingelheim Investigational Site
Tartu, Estonia
Germany
1160.63.49013 Boehringer Ingelheim Investigational Site
Darmstadt, Germany
1160.63.49018 Boehringer Ingelheim Investigational Site
Dresden, Germany
1160.63.49017 Boehringer Ingelheim Investigational Site
Dresden, Germany
1160.63.49014 Boehringer Ingelheim Investigational Site
Gießen, Germany
1160.63.49011 Boehringer Ingelheim Investigational Site
Ludwigshafen, Germany
1160.63.49010 Boehringer Ingelheim Investigational Site
Mannheim, Germany
1160.63.49005 Boehringer Ingelheim Investigational Site
Mannheim, Germany
1160.63.49007 Boehringer Ingelheim Investigational Site
München, Germany
1160.63.49009 Boehringer Ingelheim Investigational Site
Püttlingen, Germany
Italy
1160.63.39006 Boehringer Ingelheim Investigational Site
Bergamo, Italy
1160.63.39015 Boehringer Ingelheim Investigational Site
Castelfranco Veneto (TV), Italy
1160.63.39019 Boehringer Ingelheim Investigational Site
Chieti Scalo (CH), Italy
1160.63.39003 Boehringer Ingelheim Investigational Site
Cosenza, Italy
1160.63.39008 Boehringer Ingelheim Investigational Site
Fidenza (PR), Italy
1160.63.39011 Boehringer Ingelheim Investigational Site
Firenze, Italy
1160.63.39009 Boehringer Ingelheim Investigational Site
Genova, Italy
1160.63.39004 Boehringer Ingelheim Investigational Site
Milano, Italy
1160.63.39020 Boehringer Ingelheim Investigational Site
Milano, Italy
1160.63.39010 Boehringer Ingelheim Investigational Site
Milano, Italy
1160.63.39022 Boehringer Ingelheim Investigational Site
Napoli, Italy
1160.63.39001 Boehringer Ingelheim Investigational Site
Palermo, Italy
1160.63.39007 Boehringer Ingelheim Investigational Site
Pisa, Italy
1160.63.39012 Boehringer Ingelheim Investigational Site
Rimini, Italy
1160.63.39017 Boehringer Ingelheim Investigational Site
Roma, Italy
1160.63.39014 Boehringer Ingelheim Investigational Site
Treviso, Italy
1160.63.39002 Boehringer Ingelheim Investigational Site
Udine, Italy
1160.63.39016 Boehringer Ingelheim Investigational Site
Vittorio veneto (TV), Italy
Korea, Republic of
1160.63.82010 Boehringer Ingelheim Investigational Site
Gwangju-si, Korea, Republic of
1160.63.82003 Boehringer Ingelheim Investigational Site
Incheon, Korea, Republic of
1160.63.82005 Boehringer Ingelheim Investigational Site
Kyeonggi-do, Korea, Republic of
1160.63.82001 Boehringer Ingelheim Investigational Site
Kyunggi-do, Korea, Republic of
1160.63.82006 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1160.63.82011 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1160.63.82008 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1160.63.82004 Boehringer Ingelheim Investigational Site
Seoul, Korea, Republic of
1160.63.82007 Boehringer Ingelheim Investigational Site
Suwon, Korea, Republic of
Latvia
1160.63.37101 Boehringer Ingelheim Investigational Site
Daugavpils, Latvia
1160.63.37102 Boehringer Ingelheim Investigational Site
Riga, Latvia
Lithuania
1160.63.37002 Boehringer Ingelheim Investigational Site
Kaunas, Lithuania
1160.63.37001 Boehringer Ingelheim Investigational Site
Vilnius, Lithuania
Netherlands
1160.63.31010 Boehringer Ingelheim Investigational Site
Assen, Netherlands
1160.63.31006 Boehringer Ingelheim Investigational Site
Breda, Netherlands
1160.63.31007 Boehringer Ingelheim Investigational Site
Den Haag, Netherlands
1160.63.31011 Boehringer Ingelheim Investigational Site
Den Helder, Netherlands
1160.63.31012 Boehringer Ingelheim Investigational Site
Dirksland, Netherlands
1160.63.31003 Boehringer Ingelheim Investigational Site
Eindhoven, Netherlands
1160.63.31001 Boehringer Ingelheim Investigational Site
Groningen, Netherlands
1160.63.31009 Boehringer Ingelheim Investigational Site
Heerlen, Netherlands
1160.63.31008 Boehringer Ingelheim Investigational Site
Oss, Netherlands
New Zealand
1160.63.64002 Boehringer Ingelheim Investigational Site
Christchurch, New Zealand
Poland
1160.63.48010 Boehringer Ingelheim Investigational Site
Kielce, Poland
1160.63.48003 Boehringer Ingelheim Investigational Site
Poznan, Poland
1160.63.48007 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48004 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48005 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48002 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48008 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48006 Boehringer Ingelheim Investigational Site
Warsaw, Poland
1160.63.48001 Boehringer Ingelheim Investigational Site
Warsaw, Poland
Russian Federation
1160.63.07007 Boehringer Ingelheim Investigational Site
Ekaterinburg, Russian Federation
1160.63.07004 Boehringer Ingelheim Investigational Site
Kursk, Russian Federation
1160.63.07014 Boehringer Ingelheim Investigational Site
Ufa, Russian Federation
1160.63.07005 Boehringer Ingelheim Investigational Site
Yaroslavl, Russian Federation
1160.63.07006 Boehringer Ingelheim Investigational Site
Yaroslavl, Russian Federation
Singapore
1160.63.65001 Boehringer Ingelheim Investigational Site
Singapore, Singapore
South Africa
1160.63.27003 Boehringer Ingelheim Investigational Site
Cape Town, South Africa
1160.63.27007 Boehringer Ingelheim Investigational Site
Centurion, South Africa
1160.63.27009 Boehringer Ingelheim Investigational Site
Krugersdorp, South Africa
1160.63.27001 Boehringer Ingelheim Investigational Site
Somerset West, South Africa
Sweden
1160.63.46001 Boehringer Ingelheim Investigational Site
Göteborg, Sweden
1160.63.46006 Boehringer Ingelheim Investigational Site
Göteborg, Sweden
1160.63.46002 Boehringer Ingelheim Investigational Site
Lund, Sweden
1160.63.46004 Boehringer Ingelheim Investigational Site
Mölndal, Sweden
1160.63.46007 Boehringer Ingelheim Investigational Site
Skövde, Sweden
1160.63.46005 Boehringer Ingelheim Investigational Site
Stockholm, Sweden
1160.63.46003 Boehringer Ingelheim Investigational Site
Värnamo, Sweden
Switzerland
1160.63.41012 Boehringer Ingelheim Investigational Site
Basel, Switzerland
1160.63.41011 Boehringer Ingelheim Investigational Site
Bruderholz, Switzerland
1160.63.41003 Boehringer Ingelheim Investigational Site
Cham, Switzerland
1160.63.41001 Boehringer Ingelheim Investigational Site
Glarus, Switzerland
1160.63.41014 Boehringer Ingelheim Investigational Site
Luzern, Switzerland
1160.63.41016 Boehringer Ingelheim Investigational Site
Luzern 16, Switzerland
1160.63.41005 Boehringer Ingelheim Investigational Site
Schiers, Switzerland
1160.63.41009 Boehringer Ingelheim Investigational Site
Thun, Switzerland
1160.63.41022 Boehringer Ingelheim Investigational Site
Wetzikon, Switzerland
1160.63.41008 Boehringer Ingelheim Investigational Site
Zug, Switzerland
1160.63.41006 Boehringer Ingelheim Investigational Site
Zurich, Switzerland
Thailand
1160.63.66004 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1160.63.66003 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1160.63.66002 Boehringer Ingelheim Investigational Site
Bangkok, Thailand
1160.63.66001 Boehringer Ingelheim Investigational Site
Chiang Mai, Thailand
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:
Venous Thromboembolism
Venous Thrombosis
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Dabigatran
Antithrombins
Antithrombin Proteins
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 22, 2014