A Comparison of Apixaban Versus Aspirin for Preventing Stroke in Patients With Pacemakers
Overview[ - collapse ][ - ]
| Purpose | This study aims to determine if treatment with apixaban, compared with aspirin, will reduce the risk of ischemic stroke and systemic embolism in pacemaker patients with sub-clinical atrial fibrillation and additional risk factors for stroke. |
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| Condition | Pacemaker, Artificial Defibrillators, Implantable Atrial Fibrillation Stroke |
| Intervention | Drug: Apixaban Drug: aspirin |
| Phase | Phase 4 |
| Sponsor | Population Health Research Institute |
| Responsible Party | Population Health Research Institute |
| ClinicalTrials.gov Identifier | NCT01938248 |
| First Received | September 4, 2013 |
| Last Updated | September 10, 2013 |
| Last verified | September 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 4, 2013 |
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| Last Updated Date | September 10, 2013 |
| Start Date | December 2013 |
| Estimated Primary Completion Date | May 2018 |
| Current Primary Outcome Measures | Composite of ischemic stroke and systemic embolism [Time Frame: event driven duration - mean follow-up time anticipated: 3 years] [Designated as safety issue: No] |
| Current Secondary Outcome Measures | Major bleeding [Time Frame: event driven duration - mean follow-up time anticipated: 3 years] [Designated as safety issue: Yes]Major bleeding defined as: bleeding into a critical organ, requiring surgery, associated with at least a 2 g/dL drop in hemoglobin or requiring the transfusion of at least 2 units of packed red blood cells. |
Descriptive Information[ + expand ][ + ]
| Brief Title | A Comparison of Apixaban Versus Aspirin for Preventing Stroke in Patients With Pacemakers |
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| Official Title | Apixaban for the Reduction of Thrombo-Embolism Due to Sub-Clinical Atrial Fibrillation |
| Brief Summary | This study aims to determine if treatment with apixaban, compared with aspirin, will reduce the risk of ischemic stroke and systemic embolism in pacemaker patients with sub-clinical atrial fibrillation and additional risk factors for stroke. |
| Detailed Description | There are over sixty thousand Canadians with pacemakers or implanted defibrillators. More than 40% of these patients will develop sub-clinical atrial fibrillation (SCAF), which is a short-lasting, typically asymptomatic arrhythmia that would not be detected by means other than a modern, dual-chamber pacemaker. Only 15% of patients with SCAF also have clinical atrial fibrillation (AF) and until recently, the significance of isolated SCAF was debated. However; our group published the ASSERT trial, which demonstrated that in patients with hypertension, but without clinical AF, SCAF ≥ 6 minutes in duration was associated with a 2.5-fold increased risk of stroke; which among patients with CHA2DS2-VASC score > 3 was associated with a stroke risk of 2.75% per year. However; the optimal approach to stroke prevention for patients with SCAF is controversial and oral anticoagulation (OAC) is usually not employed. As OAC can prevent 60-80% of ischemic strokes in patients with clinical AF, it is critical that we determine its roll in patients with SCAF. Many patients with pacemakers and implanted defibrillators are followed semi-annually by cardiologists and nurses in device clinics and many of them have a CHA2DS2-VASC score > 3. They represent a large, high-risk and easily identifiable group of patients who are highly compliant with follow-up. ARTESiA will enroll 3,719 patients with a pacemaker or implanted defibrillator, a CHA2DS2-VASC score > 3 and at least one episode of SCAF ≥ 6 minutes who do not have a history of clinical AF and who do not have a contra-indication to oral anticoagulation. Patients will be randomized to receive either the oral anticoagulant apixaban or aspirin, in a double-blind, double-dummy fashion and will be followed for the primary outcome of ischemic stroke or systemic embolism. ARTESiA will help define the role of OAC in patients with pacemakers and defibrillations who have SCAF; providing clinicians with important guidance for this common problem. However; the implications of ARTESiA go beyond the pacemaker population. New cardiac rhythm monitoring technologies are increasingly being used in clinical practice and suggest a high prevalence of SCAF among older individuals without pacemakers, but with cardiovascular risk factors. The results of ARTESiA will give insights for this much larger and rapidly growing group of patients. |
| Study Type | Interventional |
| Study Phase | Phase 4 |
| Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention |
| Condition |
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| Intervention | Drug: Apixaban apixaban at a dose of 5 mg twice daily (2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum creatinine ≥ 133 mmol/L) Other Names: EliquisDrug: aspirin aspirin 80 - 100 mg once daily Other Names:
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Recruitment Information[ + expand ][ + ]
| Recruitment Status | Not yet recruiting |
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| Estimated Enrollment | 4000 |
| Estimated Completion Date | May 2018 |
| Estimated Primary Completion Date | December 2017 |
| Eligibility Criteria | Inclusion Criteria: Patients with a dual-chamber pacemaker or implantable defibrillator with: - At least one SCAF (subclinical atrial fibrillation) ≥ 6 minutes in duration - CHA2DS2-VASc score of > 3 - Not current receiving chronic therapy with an oral anticoagulant Exclusion Criteria: - Clinical AF documented by 12 lead ECG, or by continuous ECG monitoring, with or without clinical symptoms; OR SCAF (pacemaker/ICD-detected) of > 24 hours continuous curation - Mechanical valve prosthesis, deep vein thrombosis or pulmonary embolism or other ongoing indication for oral anticoagulation - eGFR < 25 mL/min - Use of strong inhibitors of CYP-3A4 or P-gp (i.e., clarithromycin, etc.) - Contra-indication to oral anticoagulants or ASA: - Prior intracranial hemorrhage - Platelet count < 50,000 - Ongoing need for combination therapy with aspirin and clopidogrel (or other combination of two platelet inhibitors) - Allergy to ASA - Unwilling to attend study follow-up |
| Gender | Both |
| Ages | N/A |
| Accepts Healthy Volunteers | No |
| Contacts | Contact: Heather Beresh, M.Sc 905-527-4322 heather.beresh@phri.ca |
| Location Countries | Not Provided |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01938248 |
|---|---|
| Other Study ID Numbers | ARTESiA |
| Has Data Monitoring Committee | No |
| Information Provided By | Population Health Research Institute |
| Study Sponsor | Population Health Research Institute |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Jeff Healey, M.D. Population Health Research InstitutePrincipal Investigator: Stuart Connolly, M.D. Population Health Research InstitutePrincipal Investigator: Marco Alings, M.D. Working Group Cardiovascular Research Netherlands |
| Verification Date | September 2013 |