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AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke (ARCADIA)

This study is not yet open for participant recruitment.
Verified June 2017 by Mitchell S Elkind, Columbia University
Sponsor:
ClinicalTrials.gov Identifier:
NCT03192215
First Posted: June 20, 2017
Last Update Posted: June 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
Medical University of South Carolina
Bristol-Myers Squibb
Pfizer
Roche Pharma AG
Information provided by (Responsible Party):
Mitchell S Elkind, Columbia University
  Purpose

Objectives

  • Primary: To test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in patients with cryptogenic ischemic stroke and atrial cardiopathy.
  • Secondary: To test the hypothesis that the relative efficacy of apixaban over aspirin increases with the severity of atrial cardiopathy.

Condition Intervention Phase
Stroke Drug: Apixaban Drug: Aspirin Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Active treatment will be either apixaban 5 mg or aspirin 81 mg. An adjusted dose of apixaban 2.5 mg will be used for subjects with at least two of the following: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or known serum creatinine greater than or equal to 1.5 mg/dL. There will be six possible study tablets: apixaban 5 mg (regular dose), apixaban 2.5 mg (adjusted dose), apixaban 5 mg placebo, apixaban 2.5 mg placebo, aspirin 81 mg, and aspirin placebo.

All subjects will be randomized to receive active treatment with either active apixaban or active aspirin. Study treatments will be supplied in a double-dummy fashion as apixaban 5 mg (2.5 mg for the adjusted dose) or matching placebo, and aspirin 81 mg or matching placebo.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Eligible patients will be allocated in a 1:1 ratio to apixaban or aspirin using the minimal sufficient balance randomization method to prevent serious treatment imbalances by study site.
Primary Purpose: Prevention
Official Title: AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke

Resource links provided by NLM:


Further study details as provided by Mitchell S Elkind, Columbia University:

Primary Outcome Measures:
  • Incidence of recurrent stroke [ Time Frame: 4 years ]
    Recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type)


Secondary Outcome Measures:
  • Incidence of recurrent ischemic stroke or systemic embolism [ Time Frame: Up to 4 years ]
    Secondary efficacy outcome A

  • Incidence of recurrent stroke of any type plus death from any cause [ Time Frame: Up to 4 years ]
    Secondary efficacy outcome B

  • Incidence of symptomatic intracranial hemorrhage (including symptomatic hemorrhagic transformation of an ischemic stroke). [ Time Frame: Up to 4 years ]
    Primary safety outcome A

  • Incidence of major hemorrhage other than intracranial hemorrhage [ Time Frame: Up to 4 years ]
    Primary safety outcome B

  • Incidence of death from any cause [ Time Frame: Up to 4 years ]
    Secondary safety outcome


Estimated Enrollment: 1100
Anticipated Study Start Date: September 1, 2017
Estimated Study Completion Date: April 30, 2022
Estimated Primary Completion Date: October 31, 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active agent: Apixaban
Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban
Drug: Apixaban
5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
Other Name: Eliquis
Active Comparator: Active control: Aspirin
Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin
Drug: Aspirin
Aspirin 81 mg by mouth once daily.
Other Name: Aspirin Tablet

Detailed Description:
ARCADIA is a multicenter, biomarker-driven, randomized, double-blind, active-control, phase 3 clinical trial of apixaban versus aspirin in patients who have evidence of atrial cardiopathy and a recent stroke of unknown cause. Eleven hundred subjects will be recruited over 2.5 years at 120 sites in the NINDS StrokeNet consortium. Subjects will be followed for a minimum of 1.5 years and a maximum of 4 years for the primary efficacy outcome of recurrent stroke and the primary safety outcomes of symptomatic intracranial hemorrhage and major hemorrhage other than intracranial hemorrhage.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   45 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 45 years.
  • Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
  • Modified Rankin Scale (MRS) score ≤ 4.
  • Ability to be randomized within 3 to 120 days after stroke onset.
  • ESUS, defined as all of the following2:

    • Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a subcortical (this includes pons and midbrain) infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or ≤2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following are not considered lacunes: multiple simultaneous small deep infarcts, lateral medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar stroke syndrome and no infarct on imaging are excluded.
    • Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator.
    • No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion. All patients must undergo electrocardiogram, transthoracic or transesophageal echocardiography (TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or cardiac CT will be performed at the discretion of the local treating physician and principal investigator. Additional cardiac rhythm monitoring, such as monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor, will be at the discretion of the treating physician and local principal investigator.
    • No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as toxicological screens, serological testing for syphilis, and tests for hypercoagulability, will be performed at the discretion of the treating physician and local principal investigator.

Exclusion Criteria:

  • History of AF, AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization.
  • Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.
  • Need for antiplatelet agent other than aspirin, such as clopidogrel after implantation of a coronary artery stent. Open-label therapy with aspirin up to 244 mg/day is allowed.
  • History of spontaneous intracranial hemorrhage.
  • Chronic kidney disease with serum creatinine ≥2.5 mg/dL.
  • Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.
  • Clinically significant bleeding diathesis.
  • Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).
  • Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).
  • At risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control, which includes an oral contraceptive, two methods of barrier birth control such as condom with or without spermicidal lubricant + diaphragm, or abstinence.
  • Known allergy or intolerance to aspirin or apixaban.
  • Concomitant participation in another clinical trial involving a drug or acute stroke intervention.
  • Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.
  • Inability of either participant or surrogate to provide written, informed consent for trial participation.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03192215


Contacts
Contact: Mitchell SV Elkind, MD 212 305-1710 mse13@cumc.columbia.edu
Contact: Linda V Busacca, BA 212 305-4582 lb103@cumc.columbia.edu

  Show 78 Study Locations
Sponsors and Collaborators
Columbia University
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
Medical University of South Carolina
Bristol-Myers Squibb
Pfizer
Roche Pharma AG
Investigators
Principal Investigator: Mitchell SV Elkind, MD Columbia University
  More Information

Additional Information:
Publications:
Responsible Party: Mitchell S Elkind, Professor of Neurology and Epidemiology in the Gertrude H. Serg, Department of Neurology Stroke, Columbia University
ClinicalTrials.gov Identifier: NCT03192215     History of Changes
Other Study ID Numbers: AAAR4607
1U01NS095869-01A1 ( U.S. NIH Grant/Contract )
First Submitted: June 16, 2017
First Posted: June 20, 2017
Last Update Posted: June 20, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Mitchell S Elkind, Columbia University:
Atrial Cardiopathy
Cryptogenic stroke
Ischemic stroke
Apixaban
Aspirin

Additional relevant MeSH terms:
Stroke
Heart Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Aspirin
Apixaban
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants