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

Study Overview
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Brief Summary
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The purposes of this study are: To evaluate the long-term safety of dabigatran etexilate To assess the effect of a knowledge translation intervention on patient outcomes

Official Title
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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

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: dabigatran dose 1
* Drug: dabigatran dose 2


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participation in RE-LY, requires long term anticoagulation, provides written informed consent Exclusion criteria: Permanent discontinuation of dabigatran during RE-LY

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dabigatran dose 1<br>dabigatran high dose twice daily | Drug: dabigatran dose 1<br>* dabigatran high dose twice daily<br>|
| Experimental: dabigatran dose 2<br>dabigatran low dose twice daily | Drug: dabigatran dose 2<br>* dabigatran low dose twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Bleeding, Annualized Rate of Subjects With Major Bleeds | 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 | up to 43 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stroke, Annualized Rate of Subjects With Stroke | 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 | up to 43 months | 
| Non CNS Systemic Embolism (SEE), Annualized Rate of Subjects With Non-CNS SEE | 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. | up to 43 months | 
| Pulmonary Embolism (PE), Annualized Rate of Subjects With PE | 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: an intraluminal filling defect in segmental or more proximal branches on spiral CT scan 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 a perfusion defect of at least 75% of a segment with a local normal ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS) inconclusive spiral CT, pulmonary angiography or lung scintigraphy with demonstration of DVT in the lower extremities by compression ultrasound or venography. | up to 43 months | 
| Acute Myocardial Infarction (MI), Annualized Rate of Subjects With MI | 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. | up to 43 months | 
| Deep Vein Thrombosis, Annualized Rate of Subjects With DVT | 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: abnormal compression ultrasound (CUS), an intraluminal filling defect on venography. | up to 43 months | 
| Death, Annualized Rate of Subject Death | 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. | up to 43 months | 
| Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) | 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. | up to 43 months | 
| Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE) and All Cause Death | 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. | up to 43 months | 
| Annualized Rate of Subjects With Composite Incidence of Stroke, Non CNS Systemic Embolism (SEE), Pulmonary Embolism (PE), Myocardial Infarction, Vascular Death | 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. | up to 43 months | 
| 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 | 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. | up to 43 months | 
| Annualized Rate of Subjects With Minor Bleeds | 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. | up to 43 months | 
| Annualized Rate of Subjects With Any Bleeds (Major Plus Minor) | 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. | up to 43 months | 
| Annualized Rate of Subjects With Intra-Cranial Hemorrhage (ICH) | 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. | up to 43 months |