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

Eligibility

Eligible Ages
Over 45 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 3
Study Type
Interventional
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.
Primary Purpose
Prevention
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.

Arm Groups

ArmDescriptionAssigned Intervention
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 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
  • Drug: Aspirin
    Aspirin 81 mg by mouth once daily.
    Other names:
    • Aspirin Tablet

Recruiting Locations

University of Alabama
Birmingham, Alabama 35233
Contact:
Tammy Davis
trdavis@uabmc.edu

University of South Alabama University Hospital
Mobile, Alabama 36604
Contact:
Rebecca Sugg, MD
rsugg@health.southalabama.edu

St. Joseph's Hospital and Medical Center
Phoenix, Arizona 85013
Contact:
Supreet Kaur, MD
Supreet.Kaur@DignityHealth.org

Banner University Medical Center - Tucson
Tucson, Arizona 85724
Contact:
Eddie Soto
esoto@neurology.arizona.edu

UAMS Medical Center
Little Rock, Arkansas 72205
Contact:
Amanda Harwell
aharwell@uams.edu

Eden Medical Center
Castro Valley, California 94546
Contact:
Leah Galvez
510-727-8267
galvezls@sutterhealth.org

UCSD Health La Jolla
La Jolla, California 92037
Contact:
Theresa McQuaid
tmcquaid@ucsd.edu

Sharp Grossmont Hospital
La Mesa, California 92123
Contact:
Cary Murphy
Cary.murphy@sharp.com

Long Beach Memorial Medical Center
Long Beach, California 90806
Contact:
Nima Ramezan-Arab, MD
nramezan-arab@memorialcare.org

Los Alamitos Medical Center
Los Alamitos, California 90720
Contact:
Margaret Villa, RN
Margaret.Villa@tenethealth.com

Kaiser Permanente
Los Angeles, California 90027
Contact:
Zahra Ajani, MD
Zahra.A.Ajani@kp.org

Keck Hospital Of USC
Los Angeles, California 90033
Contact:
Nerses Sanossian, MD
nsanossi@usc.edu

VA Greater Los Angeles - West LA VA Medical Center
Los Angeles, California 90073
Contact:
Roi A Wallis, MD
RoiAnn.Wallis@med.va.gov

Ronald Reagan UCLA Medical Center
Los Angeles, California 90095
Contact:
Jeffrey Saver, MD
JSaver@mednet.ucla.edu

UC Irvine Medical Center
Orange, California 92868
Contact:
Julia Fong
juliakf@hs.uci.edu

Salinas Valley Memorial Hospital
Salinas, California 93901
Contact:
Juan Morales
jmorales3@svmh.com

UCSD Medical Center - Hillcrest Hospital
San Diego, California 92103
Contact:
Theresa McQuaid
tmcquaid@ucsd.edu

San Francisco General
San Francisco, California 94110
Contact:
Claude Hemphill, MD
Claude.hemphill@ucsf.edu

UCSF Medical Center
San Francisco, California 94143
Contact:
Karl Meisel, MD
karl.meisel@ucsf.edu

Stanford University Medical Center
Stanford, California 94305
Contact:
Nirali Vora, MD
nirali@stanford.edu

Swedish Medical Center
Englewood, Colorado 80113
Contact:
Alicia Bennett, MD
abennett@carepointhc.com

St. Mary's Medical Center
Grand Junction, Colorado 81501
Contact:
Logan McDaneld, MD
logan.mcdaneld@sclhealth.org

Hartford Hospital
Hartford, Connecticut 06102-5037
Contact:
Amre Nouh, MD
amre.nouh@hhchealth.org

Yale New Haven Hospital
New Haven, Connecticut 06520
Contact:
Reshma Narula, MD
reshma.narula@yale.edu

Med-star Georgetown Univ.
Washington, District of Columbia 20007
Contact:
Andrew Stemer, MD
Andrew.b.stemer@medstar.net

Medstar Washington
Washington, District of Columbia 20010
Contact:
Amie P. Hsia, MD
Amie.Hsia@medstar.net

UF Health Shands
Gainesville, Florida 32610
Contact:
Christina S. Wilson, MD
Christina.Wilson@neurology.ufl.edu

Mayo Clinic
Jacksonville, Florida 32224
Contact:
Jaya Vijayan
Vijayan.Jaya@mayo.edu

Jackson Memorial
Miami, Florida 33136
Contact:
Erika Marulanda-Londono, MD
etm42@med.miami.edu

Univ. Miami Hospital
Miami, Florida 33136
Contact:
Erika T Marulanda-Londono, MD
etm42@med.miami.edu

Baptist Hospital of Miami
Miami, Florida 33176
Contact:
Felipe De Los Rios, MD
FelipeDL@baptisthealth.net

Intercoastal Medical Group - Hyde Park
Sarasota, Florida 34239
Contact:
Mauricio Concha, MD
mconcha@intercoastalmedical.com

Tampa General
Tampa, Florida 33606
Contact:
William S. Burgin, MD
wburgin@health.usf.edu

Emory University
Atlanta, Georgia 30303
Contact:
Fadi Nahab, MD
fnahab@emory.edu

Grady Memorial
Atlanta, Georgia 30303
Contact:
Nicolas Bianchi, MD
nicolas.a.bianchi@emory.edu

Northwestern Memorial Hospital
Chicago, Illinois 60611
Contact:
Fan Caprio, MD
fan-zhang@northwestern.edu

Rush University
Chicago, Illinois 60612
Contact:
Laurel Cherian (Smith), MD
laurel_j_smit@rush.edu

University of Illinois
Chicago, Illinois 60612
Contact:
Fernando Testai, MD
testai@uic.edu

University of Chicago Medical Center
Chicago, Illinois 60637
Contact:
James Brorson, MD
jbrorson@neurology.bsd.uchicago.edu

OSF St. Francis Medical Center
Peoria, Illinois 61637
Contact:
Mandi L Arnold
Mandi.L.Arnold@osfhealthcare.org

St. John's Hospital (Prairie Research)
Springfield, Illinois 62769
Contact:
Lauren Bainter
lbainter@prairieresearch.com

Central DuPage Hospital
Winfield, Illinois 60190
Contact:
Dhruvil PANDYA, MD
dhruvil.pandya2@nm.org

University of Iowa
Iowa City, Iowa 52242
Contact:
Enrique Leira, MD
enrique-leira@uiowa.edu

University of Kansas
Kansas City, Kansas 66160
Contact:
Aparna Pendurthi., MD
apendurthi2@kumc.edu

University of Kentucky
Lexington, Kentucky 40536
Contact:
L. Creed Pettigrew, MD, MPH
cpetti@email.uky.edu

University of Louisville Hospital
Louisville, Kentucky 40202
Contact:
Tracy Ander, MD
aljerd01@exchange.louisville.edu

Ochsner Medical Center
New Orleans, Louisiana 70121
Contact:
Richard Zweifler, MD
richard.zweifler@ochsner.org

Eastern Maine Medical Center
Bangor, Maine 04401
Contact:
Roople UNIA, MD
runia@northernlight.org

University of Maryland Medical Center
Baltimore, Maryland 21201
Contact:
Kweku Mills-Robertson
KMills-Robertson@som.umaryland.edu

Tufts Medical Center
Boston, Massachusetts 02111
Contact:
Emiliya Melkumova, MD
EMelkumova@tuftsmedicalcenter.org

Mass General Hospital
Boston, Massachusetts 02114
Contact:
Aneesh B. Singhal, MD
asinghal@partners.org

Beth Israel Deaconess Medical
Boston, Massachusetts 02215
Contact:
Sandeep Kumar, MD
skumar@bidmc.harvard.edu

Brigham & Womens Hospital
Boston, Massachusetts 20115
Contact:
Steve Feske, MD
sfeske@partners.org

U Mass Memorial Medical Center
Worcester, Massachusetts 01655
Contact:
Richard Goddeau, MD
Richard.Goddeau@umassmemorial.org

University of Michigan University Hospital
Ann Arbor, Michigan 48109
Contact:
Joseph Carrera, MD
josephfc@med.umich.edu

Detroit Receiving Hospital
Detroit, Michigan 48201
Contact:
Raymond Yost, MD
RYost@dmc.org

Henry Ford Hospital
Detroit, Michigan 48202
Contact:
Angelos Katramados, MD
akatram1@hfhs.org

McLaren Flint
Flint, Michigan 48532
Contact:
Aniel Majjhoo, MD
aniel.majjhoo@mclaren.org

Mercy Health St. Mary's
Grand Rapids, Michigan 49503
Contact:
Christopher Goshgarian, MD
Christopher.goshgarian@mercyhealth.com

McLaren Macomb, Mount Clemens, MI
Mount Clemens, Michigan 48043
Contact:
Valentyna Onishchuk
Valentyna.onishchuk@mclaren.org

Abbot Northwestern Hospital
Minneapolis, Minnesota 55407
Contact:
Mark Young, MD
myoung@noranclinic.com

Mayo Clinic
Rochester, Minnesota 55905
Contact:
Alejandro Rabinstein, MD
rabinstein.alejandro@mayo.edu

United Hospital
Saint Paul, Minnesota 55102
Contact:
Ganesh Asaithambi, MD
Ganesh.asaithambi@allina.com

University of Mississippi Medical Center
Jackson, Mississippi 39216
Contact:
Jacquelyn Collins
jcollins3@umc.edu

St. Louis University Hospital
Saint Louis, Missouri 63104
Contact:
Andre Guthrie
andre.guthrie@health.slu.edu

Barnes Jewish Hospital
Saint Louis, Missouri 63110
Contact:
Andria Ford, MD
forda@neuro.wustl.edu

Cox Medical Center South
Springfield, Missouri 65807
Contact:
Sam Atkinson
uriah.atkinson@coxhealth.com

University of Nebraska
Omaha, Nebraska 68198
Contact:
Pierre Fayad, MD
pfayad@unmc.edu

Capital Health Medical Center Hopewell
Pennington, New Jersey 08534
Contact:
Cynthia Diaz
cdiaz@capitalhealth.org

Univ. New Mexico
Albuquerque, New Mexico 87131
Contact:
Atif Zafar, MD
azafr@salud.unm.edu

Montefiore Medical Center
Bronx, New York 10467
Contact:
Kathryn Kirchoff-Torres, MD
kkirchof@montefiore.org

Kings County Hospital
Brooklyn, New York 11203
Contact:
Susan W. Law, DO
susan.law@nychhc.org

New York Presbyterian - Brooklyn Methodist Hospital
Brooklyn, New York 11215-3609
Contact:
Ji Chong, MD
jic9002@med.cornell.edu

Maimonides Medical Center
Brooklyn, New York 11219
Contact:
Sanskriti Mishra, MD
SAmishra@maimonidesmed.org

NYU Langone Hospital - Brooklyn
Brooklyn, New York 11220
Contact:
Erica Scher
Erica.scher@nyulangone.org

Mount Sinai Beth Israel Brooklyn
Brooklyn, New York 11234
Contact:
Holly Morhaim
Holly.morhaim@mountsinai.org

Buffalo General Medical Center
Buffalo, New York 14203
Contact:
Robert N Sawyer, MD
Robertsa@buffalo.edu

North Shore University Hospital
Manhasset, New York 11042
Contact:
Prathusan SUBRAMANIAM
psubramaniam@northwell.edu

NYU Langone
New York, New York 10003
Contact:
Jose Torres, MD
jose.torres2@nyumc.org

Mount Sinai West
New York, New York 10019
Contact:
Carolyn Brockington, MD
cbrockin@chpnet.org

Columbia University Medical Center
New York, New York 10032
Contact:
Michell SV Elkind, MD
212-305-1710
mse13@cumc.columbia.edu

Weill Cornell Medicine
New York, New York 10065
Contact:
Hooman Kamel, MD
hok9010@med.cornell.edu

Lenox Hill Hospital
New York, New York 10075
Contact:
Martha Karran
mkarran@northwell.edu

Strong Memorial Hospital
Rochester, New York 14642
Contact:
Emily Prentiss
Emily_Prentiss@urmc.rochester.edu

Moses H. Cone Memorial Hospital
Greensboro, North Carolina 27405
Contact:
Rizwan Sabir
rizwan.sabir@gnr.clinic

Wake Forest Baptist Medical Center
Winston-Salem, North Carolina 27157
Contact:
Krystal Schmidt
kschmidt@wakehealth.edu

Akron General Medical Center
Akron, Ohio 44307
Contact:
James Gebel, MD
GebelJ2@ccf.org

University of Cincinnati
Cincinnati, Ohio 45219
Contact:
Pooja Khatri, MD
khatrip@ucmail.uc.edu

Louis Stokes VA Medical Center
Cleveland, Ohio 44106
Contact:
Svetlana Pundik, MD
877-838-8262
sxp19@case.edu

UH Cleveland Medical Center
Cleveland, Ohio 44106
Contact:
Sophia Sundararajan, MD
Sophia.Sundararajan@UHhospitals.org

Cleveland Clinic
Cleveland, Ohio 44195
Contact:
Dolora Wisco, MD
WISCOD@ccf.org

OSU Wexner
Columbus, Ohio 43210
Contact:
Shraddha Mainali, MD
Shraddha.Mainali@osumc.edu

Miami Valley Hospita
Dayton, Ohio 45409
Contact:
Linda Clark
lclark@premierhealth.com

Mercy Health St Vincent
Toledo, Ohio 43608
Contact:
Osama Zaidat, MD
OZaidat@mercy.com

OU Medical Center Oklahoma
Oklahoma City, Oklahoma 73104
Contact:
Evgeny Sidorov, MD
evgeny-sidorov@ouhsc.edu

Oregon Health and Sciences
Portland, Oregon 97239
Contact:
Hormozd Bozorgchami, MD
bozorgch@ohsu.edu

Lehigh Valley Hospital
Allentown, Pennsylvania 18103
Contact:
Hussam A Yacoub, MD
Hussam_A.Yacoub@lvhn.org

Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania 19104
Contact:
Scott Kasner, MD
kasner@mail.med.upenn.edu

UPMC Presbyterian
Pittsburgh, Pennsylvania 15213
Contact:
Matthew Starr, MD
starrmt2@upmc.edu

Rhode Island Hospital
Providence, Rhode Island 02903
Contact:
Scott Moody
Scott.Moody@Lifespan.org

Medical University of South Carolina
Charleston, South Carolina 29425
Contact:
Christine Holmsted, MD
holmsted@musc.edu

Prisma Health Richland Hospital (formerly Palmetto Health)
Columbia, South Carolina 29203
Contact:
Sen Souvik, MD
Souvik.Sen@uscmed.sc.edu

Greenville Hospital System
Greenville, South Carolina 29605
Contact:
Victoria Holt
Tory.Holt@prismahealth.org

Methodist University Hospital
Memphis, Tennessee 38104
Contact:
Balaji KRISHNAIAH, MD
bkrishn4@uthsc.edu

Vanderbilt
Nashville, Tennessee 37212
Contact:
Michael Froehler, MD
m.froehler@vanderbilt.edu

UT Southwestern Medical Center
Dallas, Texas 75390
Contact:
Ty Shang, MD
Ty.Shang@UTSouthwestern.edu

DHR Health
Edinburg, Texas 78539
Contact:
Wady Aude, MD
wady.aude@UTRGV.edu

Valley Bapist
Harlingen, Texas 78550
Contact:
Ameer Hassan, MD
Ameer.hassan@valleybaptist.net

Baylor College College of Medicine
Houston, Texas 77030
Contact:
Rahul Damani, MD
Rahul.Damani@bcm.edu

Houston Methodist Hospital
Houston, Texas 77030
Contact:
Vivek Misra, MD
vmisra@houstonmethodist.org

Memorial Hermann Texas Medical Center
Houston, Texas 77030
Contact:
Anjail Z. Sharrief, MD
Anjail.Z.Sharrief@uth.tmc.edu

Univ of Texas Health Science Center San Antonio
San Antonio, Texas 78229
Contact:
Reza Behrouz, MD
Behrouz@uthscsa.edu

Univ of Utah
Salt Lake City, Utah 84132
Contact:
Peter M. Hannon, MD
Peter.Hannon@hsc.utah.edu

George E Whalen VA
Salt Lake City, Utah 84148
Contact:
Jana Wold, MD
Jana.Wold@hsc.utah.edu

UVA Medical Center
Charlottesville, Virginia 22908
Contact:
Andrew Southerland, MD
as5ef@virginia.edu

Bon Secours St. Mary's Hospital
Richmond, Virginia 23226
Contact:
Kelly Patterson
Kelly_Patterson@bshsi.org

Harborview Medical Center
Seattle, Washington 98104
Contact:
David Tirschwell, MD
tirsch@uw.edu

Swedish Medical Center - Cherry Hill Campus
Seattle, Washington 98122
Contact:
Emily Ho, MD
emily.ho@swedish.org

WVU Healthcare Ruby Memorial
Morgantown, West Virginia 26506-9180
Contact:
Alvi Muhammad, MD
muhammad.alvi@hsc.wvu.edu

Froedtert Hospital
Milwaukee, Wisconsin 53226
Contact:
Tiffany Morse
tmorse@mcw.edu

More Details

NCT ID
NCT03192215
Status
Recruiting
Sponsor
Columbia University

Study Contact

Mitchell SV Elkind, MD
212 305-1710
mse13@cumc.columbia.edu

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 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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.