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

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ClinicalTrials.gov Identifier: NCT03192215
Recruitment Status : Recruiting
First Posted : June 20, 2017
Last Update Posted : March 19, 2019
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
Medical University of South Carolina
Bristol-Myers Squibb
Pfizer
Roche Pharma AG
Weill Medical College of Cornell University
University of Washington
Information provided by (Responsible Party):
Mitchell S Elkind, Columbia University

Tracking Information
First Submitted Date  ICMJE June 16, 2017
First Posted Date  ICMJE June 20, 2017
Last Update Posted Date March 19, 2019
Actual Study Start Date  ICMJE January 19, 2018
Estimated Primary Completion Date January 18, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
Incidence of recurrent stroke [ Time Frame: 4 years ]
Recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03192215 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2017)
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
Official Title  ICMJE AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
Brief Summary

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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE Stroke
Intervention  ICMJE
  • Drug: Apixaban
    5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
    Other Name: Eliquis
  • Drug: Aspirin
    Aspirin 81 mg by mouth once daily.
    Other Name: Aspirin Tablet
Study Arms  ICMJE
  • Experimental: Active agent: Apixaban
    Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban
    Intervention: Drug: Apixaban
  • Active Comparator: Active control: Aspirin
    Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin
    Intervention: Drug: Aspirin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 16, 2017)
1100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2022
Estimated Primary Completion Date January 18, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 following:

    • 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, such as aspirin or clopidogrel
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Mitchell SV Elkind, MD 212 305-1710 mse13@cumc.columbia.edu
Contact: Daniel A Velez, BA 212 305-7755 dav2125@cumc.columbia.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03192215
Other Study ID Numbers  ICMJE AAAR4607
1U01NS095869-01A1 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Mitchell S Elkind, Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE
  • National Institute of Neurological Disorders and Stroke (NINDS)
  • University of Cincinnati
  • Medical University of South Carolina
  • Bristol-Myers Squibb
  • Pfizer
  • Roche Pharma AG
  • Weill Medical College of Cornell University
  • University of Washington
Investigators  ICMJE
Principal Investigator: Mitchell SV Elkind, MD Columbia University
PRS Account Columbia University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP