RELY-ABLE Long Term Multi-center Extension of Dabigatran Treatment in Patients With Atrial Fibrillation Who Completed RE-LY Trial

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00808067
First received: December 12, 2008
Last updated: June 3, 2014
Last verified: March 2014
  Purpose

The purposes of this study are:

  1. To evaluate the long-term safety of dabigatran etexilate
  2. To assess the effect of a knowledge translation intervention on patient outcomes

Condition Intervention Phase
Atrial Fibrillation
Drug: dabigatran dose 1
Drug: dabigatran dose 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: RELY-ABLE Long Term Multi-center Extension of Dabigatran Treatment in Patients With Atrial Fibrillation Who Completed the RE-LY Trial and a Cluster Randomised Trial to Assess the Effect of a Knowledge Translation Intervention on Patient Outcomes

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Major Bleeding, Annualized Rate of Subjects With Major Bleeds [ Time Frame: up to 43 months ] [ Designated as safety issue: Yes ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Major bleeding must have satisfied one or more of the following criteria:

    • Bleeding associated with a reduction in hemoglobin of at least 20 g/L
    • Required transfusion of at least 2 units of blood or packed cells
    • Symptomatic bleeding in a critical area or organ: intraocular, intraspinal, intramuscular with compartment syndrome, retroperitoneal, intra-articular, pericardial, gastrointestinal

    Major bleed were classified as life-threatening if they met one or more of the following criteria:

    • Reduction in hemoglobin of at least 50 g/L
    • Transfusion of at least 4 units of blood or packed cells
    • Symptomatic intracranial bleeding, either subdural or intracerebral
    • Associated with hypotension requiring use of intravenous inotropic agents
    • Required surgical intervention to stop bleeding
    • Resulted in death


Secondary Outcome Measures:
  • Stroke, Annualized Rate of Subjects With Stroke [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Stroke was an acute onset of a focal neurological deficit of presumed vascular origin lasting for 24 hours or more or resulting in death. The stroke was categorized as ischemic or hemorrhagic or cause unknown based on computerized tomography (CT), magnetic resonance (MR) scanning or autopsy. Fatal stroke was defined as death from any cause within 30 days of stroke. Severity of stroke was assessed by modified Rankin score at discharge from hospital


  • Non CNS Systemic Embolism (SEE), Annualized Rate of Subjects With Non-CNS SEE [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Systemic embolism was an acute vascular occlusion of the extremities or any organ (kidneys, mesenteric arteries, spleen, retina or grafts), and was to be documented by angiography, surgery, scintigraphy, or autopsy.


  • Pulmonary Embolism (PE), Annualized Rate of Subjects With PE [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Pulmonary Embolism was generally documented by one of the following:

    1. an intraluminal filling defect in segmental or more proximal branches on spiral CT scan
    2. an intraluminal filling defect or an extension of an existing defect or a sudden cutoff of vessels more than 2.5 mm in diameter on the pulmonary angiogram
    3. a perfusion defect of at least 75% of a segment with a local normal ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
    4. inconclusive spiral CT, pulmonary angiography or lung scintigraphy with demonstration of DVT in the lower extremities by compression ultrasound or venography.

  • Acute Myocardial Infarction (MI), Annualized Rate of Subjects With MI [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    a. In subjects not undergoing PCI or CABG a subject should have fulfilled at least 2 of the following: i. Typical prolonged severe chest pain or related symptoms or signs suggestive of MI. ii. Elevation of troponin or CK-MB to more than upper level of normal (ULN) or, if CK-MB was elevated at baseline, re-elevation to more than 50% increase above the previous level. iii. Development of significant Q-waves in at least 2 adjacent ECG leads. b. After percutaneous coronary intervention (within 24h). c. After coronary artery bypass grafting (within 72h). d. Silent myocardial infarction. e. Myocardial infarction could also have been demonstrated at autopsy.


  • Deep Vein Thrombosis, Annualized Rate of Subjects With DVT [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Deep Vein Thrombosis (DVT) was generally documented by one of the following:

    1. abnormal compression ultrasound (CUS),
    2. an intraluminal filling defect on venography.

  • Death, Annualized Rate of Subject Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Deaths were classified as being vascular (sudden/arrhythmic, pump failure death, or other vascular, including bleeding) or non-vascular, due to other specified causes (e.g., malignancy), or of unknown etiology.


  • Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  • Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) and All Cause Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  • Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE), Pulmonary Embolism (PE), Myocardial Infarction, Vascular Death [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  • Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE), Pulmonary Embolism (PE), Myocardial Infarction (MI), All Cause Death and Major Bleed [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  • Annualized Rate of Subjects With Minor Bleeds [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]

    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

    Minor bleeds were clinical bleeds that did not fulfill the criteria for major bleeds. Minor bleeds were classified as associated with study medication discontinuation (temporary or permanent) or not.


  • Annualized Rate of Subjects With Any Bleeds (Major Plus Minor) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.

  • Annualized Rate of Subjects With Intra-Cranial Hemorrhage (ICH) [ Time Frame: up to 43 months ] [ Designated as safety issue: No ]
    Annualized event rate (%) = 100 * No. subjects with event / subject-years. Subject-years = Sum (date of last visit - date of first dose + 1) of all subjects / 365.25.


Enrollment: 5897
Study Start Date: November 2008
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dabigatran dose 1
dabigatran high dose twice daily
Drug: dabigatran dose 1
dabigatran high dose twice daily
Experimental: dabigatran dose 2
dabigatran low dose twice daily
Drug: dabigatran dose 2
dabigatran low dose twice daily

  Eligibility

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

Inclusion criteria:

Participation in RE-LY, requires long term anticoagulation, provides written informed consent

Exclusion criteria:

Permanent discontinuation of dabigatran during RE-LY

  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: NCT00808067

  Show 567 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: NCT00808067     History of Changes
Other Study ID Numbers: 1160.71, 2008-005248-17
Study First Received: December 12, 2008
Results First Received: December 20, 2013
Last Updated: June 3, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Austria: Medicines and Medical Devices Agency
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: Food and Drug Administration
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: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM), Kurt-Georg-Kiesinger-Allee 3, D-53175 Bonn
Great Britain: MHRA
Greece: National Organization fo Medicines (EOF) National Ethics Committe
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy (OGYI), H-1051 Budapest
India: Drug Control General of India
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Korea, Republic of: Korea Food and Drug Administration (KFDA)
Malaysia: Drug Control Authority
Netherlands: Central Committee on Research Involving Human Subjects (CCMO)
Norway: Norwegian Medicines Agency (Statens Legemiddelverk)
Philippines: Bureau of Food and Drug
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: INFARMED I.P.
Romania: National Medicines Agency, Bucharest
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
Slovakia: SUKL (state institute for drug control), SK-825 08 Bratislava 26
Sweden: Medical Products Agency Regional Ethics Committee of Uppsala
Switzerland: Swissmedic
Taiwan: Department of Health, Executive Yuan, Taiwan
Thailand: Thai Food & Drug Administration
United States: Food and Drug Administration

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Dabigatran
Antithrombins
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 16, 2014