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

• ClinicalTrials.gov Identifier: NCT00808067
• Recruitment Status: Completed
• First Posted: December 15, 2008
• Results First Posted: April 8, 2014
• Last Update Posted: June 9, 2014
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Tracking Information

• First Submitted Date: December 12, 2008
• First Posted Date: December 15, 2008
• Results First Submitted Date: December 20, 2013
• Results First Posted Date: April 8, 2014
• Last Update Posted Date: June 9, 2014
• Study Start Date: November 2008
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 3, 2014)

Major Bleeding, Annualized Rate of Subjects With Major Bleeds [ Time Frame: up to 43 months ]

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

• Original Primary Outcome Measures (submitted: December 12, 2008): Since the objective of this trial is safety, there are no primary efficacy endpoints. Safety will primarily be determined by the occurence of major bleeding. [ Time Frame: up to 28 months ]

Current Secondary Outcome Measures (submitted: March 3, 2014)

• Stroke, Annualized Rate of Subjects With Stroke [ Time Frame: up to 43 months ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

• Original Secondary Outcome Measures (submitted: December 12, 2008): The secondary endpoint is the individual and composite incidence of stroke, non CNS systemic embolism, pulmonary embolism, acute myocardial infarction, deep vein thrombosis and all deaths. [ Time Frame: up to 28 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Atrial Fibrillation

Intervention

• Drug: dabigatran dose 1
  dabigatran high dose twice daily
• Drug: dabigatran dose 2
  dabigatran low dose twice daily

Study Arms

• Experimental: dabigatran dose 1
  dabigatran high dose twice daily
  Intervention: Drug: dabigatran dose 1
• Experimental: dabigatran dose 2
  dabigatran low dose twice daily
  Intervention: Drug: dabigatran dose 2

• Publications *: Connolly SJ, Wallentin L, Ezekowitz MD, Eikelboom J, Oldgren J, Reilly PA, Brueckmann M, Pogue J, Alings M, Amerena JV, Avezum A, Baumgartner I, Budaj AJ, Chen JH, Dans AL, Darius H, Di Pasquale G, Ferreira J, Flaker GC, Flather MD, Franzosi MG, Golitsyn SP, Halon DA, Heidbuchel H, Hohnloser SH, Huber K, Jansky P, Kamensky G, Keltai M, Kim SS, Lau CP, Le Heuzey JY, Lewis BS, Liu L, Nanas J, Omar R, Pais P, Pedersen KE, Piegas LS, Raev D, Smith PJ, Talajic M, Tan RS, Tanomsup S, Toivonen L, Vinereanu D, Xavier D, Zhu J, Wang SQ, Duffy CO, Themeles E, Yusuf S. The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study. Circulation. 2013 Jul 16;128(3):237-43. doi: 10.1161/CIRCULATIONAHA.112.001139. Epub 2013 Jun 14.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 3, 2014): 5897
• Original Estimated Enrollment (submitted: December 12, 2008): 8000
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criteria:

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

Exclusion criteria:

Permanent discontinuation of dabigatran during RE-LY

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Israel, Italy, Korea, Republic of, Malaysia, Netherlands, Norway, Philippines, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, Sweden, Switzerland, Taiwan, Thailand, United Kingdom, United States
• Removed Location Countries: Ukraine

Administrative Information

• NCT Number: NCT00808067
• Other Study ID Numbers: 1160.71; 2008-005248-17 ( EudraCT Number: EudraCT )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Boehringer Ingelheim
• Original Responsible Party: Boehringer Ingelheim, Study Chair, Boehringer Ingelheim
• Current Study Sponsor: Boehringer Ingelheim
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

• PRS Account: Boehringer Ingelheim
• Verification Date: March 2014