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

June 6, 2023 updated by: Randolph S. Marshall, MD, Columbia University

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 up to 200 sites in and out of the NINDS StrokeNet consortium. Subjects will be followed for a minimum of 1.5 years and a maximum of 7 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

Interventional

Enrollment (Actual)

1015

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alberta
      • Calgary, Alberta, Canada, T2N2T9
        • University of Calgary - Foothills Medical Centre
      • Edmonton, Alberta, Canada, T6G 2G3
        • University of Alberta Hospital
      • Lethbridge, Alberta, Canada, T1J 0N9
        • Neurologic Research Center
    • British Columbia
      • Kelowna, British Columbia, Canada, V1Y 1T2
        • Kelowna General Hospital
      • Vancouver, British Columbia, Canada, V5Z 1M9
        • Vancouver General Hospital
    • Manitoba
      • Brandon, Manitoba, Canada, R7A 2B3
        • Brandon Regional Health Center
    • Ontario
      • Hamilton, Ontario, Canada, L8L2X2
        • Hamilton General Hospital
      • Kingston, Ontario, Canada, K7L2V7
        • Kingston General Hospital
      • London, Ontario, Canada, N6A 5A5
        • London Health Sciences Center
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Center
    • Quebec
      • Québec, Quebec, Canada, G1J 1Z4-65543
        • Enfant-Jesus Hospital
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N0W8
        • Royal University Hospital
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama
      • Mobile, Alabama, United States, 36604
        • University of South Alabama University Hospital
    • Arizona
      • Chandler, Arizona, United States, 85224
        • Chandler Regional Medical Center Chandler, AZ
      • Phoenix, Arizona, United States, 85013
        • St. Joseph's Hospital and Medical Center
      • Tucson, Arizona, United States, 85724
        • Banner University Medical Center - Tucson
    • California
      • Carmichael, California, United States, 95608
        • Mercy San Juan Medical Center (Dignity Health)
      • Castro Valley, California, United States, 94546
        • Eden Medical Center
      • Downey, California, United States, 90242
        • Rancho Los Amigos National Rehabilitation Center
      • Fountain Valley, California, United States, 92708
        • Fountain Valley Regional Hospital and Medical Center
      • Fresno, California, United States, 93721
        • Community Regional Medical Center
      • La Jolla, California, United States, 92037
        • UCSD Health La Jolla
      • La Mesa, California, United States, 92123
        • Sharp Grossmont Hospital
      • Long Beach, California, United States, 90806
        • Long Beach Memorial Medical Center
      • Los Alamitos, California, United States, 90720
        • Los Alamitos Medical Center
      • Los Angeles, California, United States, 90095
        • Ronald Reagan UCLA Medical Center
      • Los Angeles, California, United States, 90033
        • Keck Hospital of USC
      • Los Angeles, California, United States, 90027
        • Kaiser Permanente
      • Los Angeles, California, United States, 90033
        • Los Angeles County- USC Medical Center
      • Los Angeles, California, United States, 90073
        • VA Greater Los Angeles - West LA VA Medical Center
      • Orange, California, United States, 92868
        • UC Irvine Medical Center
      • Sacramento, California, United States, 95816
        • Sutter Medical Center
      • Salinas, California, United States, 93901
        • Salinas Valley Memorial Hospital
      • San Diego, California, United States, 92123
        • Sharp Memorial Hospital
      • San Diego, California, United States, 91910
        • Scripps Mercy
      • San Diego, California, United States, 92103
        • UCSD Medical Center - Hillcrest Hospital
      • San Diego, California, United States, 92123
        • Kaiser Permanent San Diego Medical Center
      • San Francisco, California, United States, 94143
        • UCSF Medical Center
      • San Francisco, California, United States, 94110
        • San Francisco General
      • San Jose, California, United States, 95124
        • Good Samaritan
      • Stanford, California, United States, 94305
        • Stanford University Medical Center
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Swedish Medical Center
      • Grand Junction, Colorado, United States, 81501
        • St. Mary's Medical Center
    • Connecticut
      • Bridgeport, Connecticut, United States, 06606
        • St. Vincent's Medical Center
      • Hartford, Connecticut, United States, 06102-5037
        • Hartford Hospital
      • New Haven, Connecticut, United States, 06520
        • Yale New Haven Hospital
    • Delaware
      • Newark, Delaware, United States, 19718
        • Christiana Hospital
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • MedStar Washington
      • Washington, District of Columbia, United States, 20007
        • Med-star Georgetown Univ.
    • Florida
      • Boca Raton, Florida, United States, 33486
        • Boca Raton Regional Hospital
      • Gainesville, Florida, United States, 32610
        • UF Health Shands
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
      • Jacksonville, Florida, United States, 32207
        • Baptist Medical Center Jacksonville
      • Miami, Florida, United States, 33176
        • Baptist Hospital of Miami
      • Miami, Florida, United States, 33136
        • Jackson Memorial
      • Miami, Florida, United States, 33136
        • Univ. Miami Hospital
      • Sarasota, Florida, United States, 34239
        • Intercoastal Medical Group - Hyde Park
      • Tampa, Florida, United States, 33606
        • Tampa General
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory University
      • Atlanta, Georgia, United States, 30303
        • Grady Memorial
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • The Queen's Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Chicago, Illinois, United States, 60612
        • University of Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University
      • Peoria, Illinois, United States, 61637
        • OSF St. Francis Medical Center
      • Springfield, Illinois, United States, 62702
        • Southern Illinois University Memorial Medical Center
      • Springfield, Illinois, United States, 62769
        • St. John's Hospital (Prairie Research)
      • Winfield, Illinois, United States, 60190
        • Central DuPage Hospital
    • Iowa
      • Des Moines, Iowa, United States, 50309
        • Multi-Specialty - Methodist Plaza/Unity Point
      • Iowa City, Iowa, United States, 52242
        • University of Iowa
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky
      • Lexington, Kentucky, United States, 40503
        • Baptist Health Lexington
      • Louisville, Kentucky, United States, 40202
        • University of Louisville Hospital
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Medical Center
    • Maine
      • Bangor, Maine, United States, 04401
        • Eastern Maine Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
      • Boston, Massachusetts, United States, 02111
        • Tufts Medical Center
      • Boston, Massachusetts, United States, 02118
        • Boston Medical Center
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical
      • Boston, Massachusetts, United States, 20115
        • Brigham & Womens Hospital
      • Burlington, Massachusetts, United States, 01805
        • Lahey Hospital & Medical Center
      • Worcester, Massachusetts, United States, 01655
        • U Mass Memorial Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan University Hospital
      • Ann Arbor, Michigan, United States, 48109
        • VA Ann Arbor Healthcare System
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Detroit, Michigan, United States, 48201
        • Detroit Receiving Hospital
      • Flint, Michigan, United States, 48532
        • McLaren Flint
      • Grand Rapids, Michigan, United States, 49503
        • Spectrum Health
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health St. Mary's
      • Mount Clemens, Michigan, United States, 48043
        • McLaren Macomb, Mount Clemens, MI
      • Petoskey, Michigan, United States, 49770
        • McLaren Northern Michigan
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Abbott Northwestern Hospital
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County
      • Minneapolis, Minnesota, United States, 55455
        • Univ. of Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Saint Paul, Minnesota, United States, 55101
        • Regions Hospital, St. Paul
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • University of Mississippi Medical Center
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Luke's Hospital of Kansas City
      • Saint Louis, Missouri, United States, 63110
        • Barnes Jewish Hospital
      • Saint Louis, Missouri, United States, 63104
        • St. Louis University Hospital
      • Springfield, Missouri, United States, 65807
        • Cox Medical Center South
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska
      • Omaha, Nebraska, United States, 68124
        • CHI Health Immanuel
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Cooper University Hospital,
      • New Brunswick, New Jersey, United States, 08901
        • Robert Wood Johnson
      • Pennington, New Jersey, United States, 08534
        • Capital Health Medical Center Hopewell
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131
        • Univ. New Mexico
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
      • Brooklyn, New York, United States, 11219
        • Maimonides Medical Center
      • Brooklyn, New York, United States, 11203
        • Kings County Hospital
      • Brooklyn, New York, United States, 11220
        • NYU Langone Hospital - Brooklyn
      • Brooklyn, New York, United States, 11215-3609
        • New York Presbyterian - Brooklyn Methodist Hospital
      • Brooklyn, New York, United States, 11234
        • Mount Sinai Beth Israel Brooklyn
      • Buffalo, New York, United States, 14203
        • Buffalo General Medical Center
      • Manhasset, New York, United States, 11042
        • North Shore University Hospital
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Weill Cornell Medicine
      • New York, New York, United States, 10019
        • Mount Sinai West
      • New York, New York, United States, 10075
        • Lenox Hill Hospital
      • New York, New York, United States, 10003
        • NYU Langone
      • Rochester, New York, United States, 14642
        • Strong Memorial Hospital
    • North Carolina
      • Greensboro, North Carolina, United States, 27405
        • Moses H. Cone Memorial Hospital
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Medical Center
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • Sanford Medical Center Fargo
    • Ohio
      • Akron, Ohio, United States, 44307
        • Akron General Medical Center
      • Cincinnati, Ohio, United States, 45219
        • University of Cincinnati
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44106
        • UH Cleveland Medical Center
      • Cleveland, Ohio, United States, 44106
        • Louis Stokes VA Medical Center
      • Columbus, Ohio, United States, 43210
        • OSU Wexner
      • Columbus, Ohio, United States, 43214
        • Ohio Health Riverside - Riverside Methodist Hospital
      • Dayton, Ohio, United States, 45409
        • Miami Valley Hospita
      • Toledo, Ohio, United States, 43608
        • Mercy St Vincent Medical Center
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • OU Medical Center Oklahoma
    • Oregon
      • Portland, Oregon, United States, 97227
        • Legacy Emanuel
      • Portland, Oregon, United States, 97239
        • Oregon Health and Sciences
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18103
        • LeHigh Valley Hospital
      • Altoona, Pennsylvania, United States, 16601
        • UPMC Altoona
      • Lancaster, Pennsylvania, United States, 17602
        • Lancaster General Hospital
      • Philadelphia, Pennsylvania, United States, 19104
        • Hospital of the University of Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
      • Philadelphia, Pennsylvania, United States, 19140
        • Temple University
      • Pittsburgh, Pennsylvania, United States, 15212
        • Allegheny General Hospital
      • Pittsburgh, Pennsylvania, United States, 15213
        • UPMC Presbyterian
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
      • Columbia, South Carolina, United States, 29203
        • Prisma Health Richland Hospital (formerly Palmetto Health)
      • Greenville, South Carolina, United States, 29605
        • Prisma Health Greenville Memorial Hospital
    • Tennessee
      • Memphis, Tennessee, United States, 38104
        • Methodist University Hospital
      • Nashville, Tennessee, United States, 37212
        • Vanderbilt
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center
      • Harlingen, Texas, United States, 78550
        • Valley Bapist
      • Houston, Texas, United States, 77030
        • Houston Methodist Hospital
      • Houston, Texas, United States, 77030
        • Memorial Hermann Texas Medical Center
      • Houston, Texas, United States, 77030
        • Baylor College College of Medicine
      • San Antonio, Texas, United States, 78229
        • Univ of Texas Health Science Center San Antonio
      • Temple, Texas, United States, 76508
        • Scott & White Memorial Hospital - Temple
      • The Woodlands, Texas, United States, 77380
        • Memorial Hermann The Woodlands Hospital
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Provo, Utah, United States, 84604
        • Utah Valley Regional Medical Center
      • Salt Lake City, Utah, United States, 84132
        • Univ of Utah
      • Salt Lake City, Utah, United States, 84148
        • George E Whalen VA
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • UVA Medical Center
      • Richmond, Virginia, United States, 23226
        • Bon Secours St. Mary's Hospital
    • Washington
      • Olympia, Washington, United States, 98506
        • Providence St. Peter Hospital
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center
      • Seattle, Washington, United States, 98108
        • Puget Sound VA
      • Seattle, Washington, United States, 98122
        • Swedish Medical Center - Cherry Hill Campus
    • West Virginia
      • Morgantown, West Virginia, United States, 26506-9180
        • WVU Healthcare Ruby Memorial
    • Wisconsin
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

43 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 180 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, moderate or severe 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 atrial fibrillation (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.For Canadian sites only, estimated creatinine clearance (eCrCl) <15 mL/min is also an exclusion criterion.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Active agent: Apixaban
Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban
5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
Other Names:
  • Eliquis
Active Comparator: Active control: Aspirin
Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin
Aspirin 81 mg by mouth once daily.
Other Names:
  • Aspirin Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of recurrent stroke
Time Frame: 7 years
Recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type)
7 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of recurrent ischemic stroke or systemic embolism
Time Frame: Up to 7 years
Secondary efficacy outcome A
Up to 7 years
Incidence of recurrent stroke of any type plus death from any cause
Time Frame: Up to 7 years
Secondary efficacy outcome B
Up to 7 years
Incidence of symptomatic intracranial hemorrhage (including symptomatic hemorrhagic transformation of an ischemic stroke).
Time Frame: Up to 7 years
Primary safety outcome A
Up to 7 years
Incidence of major hemorrhage other than intracranial hemorrhage
Time Frame: Up to 7 years
Primary safety outcome B
Up to 7 years
Incidence of death from any cause
Time Frame: Up to 7 years
Secondary safety outcome
Up to 7 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 19, 2018

Primary Completion (Actual)

March 31, 2023

Study Completion (Actual)

April 17, 2023

Study Registration Dates

First Submitted

June 16, 2017

First Submitted That Met QC Criteria

June 16, 2017

First Posted (Actual)

June 20, 2017

Study Record Updates

Last Update Posted (Actual)

June 7, 2023

Last Update Submitted That Met QC Criteria

June 6, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

To share individual participant data (IPD) of baseline characteristics, follow up, outcomes, etc. based on NIH/NINDS requirements.

IPD Sharing Time Frame

As per NIH/NINDS requirements.

IPD Sharing Access Criteria

All items required by NIH/NINDS will be publicly shared.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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