A Comparison of Apixaban Versus Aspirin for Preventing Stroke in Patients With Pacemakers (ARTESiA)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified September 2013 by Population Health Research Institute
Sponsor:
Information provided by (Responsible Party):
Jeff Healey, Population Health Research Institute
ClinicalTrials.gov Identifier:
NCT01938248
First received: September 4, 2013
Last updated: September 10, 2013
Last verified: September 2013
  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.


Condition Intervention Phase
Pacemaker, Artificial
Defibrillators, Implantable
Atrial Fibrillation
Stroke
Drug: Apixaban
Drug: aspirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Apixaban for the Reduction of Thrombo-Embolism Due to Sub-Clinical Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Population Health Research Institute:

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 ]

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.


Estimated Enrollment: 4000
Study Start Date: December 2013
Estimated Study Completion Date: May 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Control
Aspirin 80-100 mg once daily
Drug: aspirin
aspirin 80 - 100 mg once daily
Other Names:
  • ASA
  • acetylsalicylic acid
Experimental: Intervention
Apixaban, 5 mg twice daily (or 2.5 mg twice daily if 2 or more of: age > 80, weight ≤ 60 kg or serum creatinine ≥ 133 mmol/L)
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 Name: Eliquis

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01938248

Contacts
Contact: Heather Beresh, M.Sc 905-527-4322 ext 40351 heather.beresh@phri.ca
Contact: Ellison Themeles, M.Sc 905-527-4322 ext 40488 ellison.themeles@phri.ca

Sponsors and Collaborators
Population Health Research Institute
Investigators
Principal Investigator: Jeff Healey, M.D. Population Health Research Institute
Principal Investigator: Stuart Connolly, M.D. Population Health Research Institute
Principal Investigator: Marco Alings, M.D. Working Group Cardiovascular Research Netherlands
  More Information

No publications provided

Responsible Party: Jeff Healey, Co-Principal Investigator, Population Health Research Institute
ClinicalTrials.gov Identifier: NCT01938248     History of Changes
Other Study ID Numbers: ARTESiA
Study First Received: September 4, 2013
Last Updated: September 10, 2013
Health Authority: Canada: Canadian Institutes of Health Research
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Population Health Research Institute:
Pacemaker, Artificial
Defibrillators, Implantable
Atrial Fibrillation
Stroke Risk

Additional relevant MeSH terms:
Atrial Fibrillation
Stroke
Cerebral Infarction
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Brain Infarction
Brain Ischemia
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents

ClinicalTrials.gov processed this record on July 22, 2014