NCT03192215

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,015

participants targeted

Target at P75+ for phase_3 stroke

Timeline
Completed

Started Jan 2018

Typical duration for phase_3 stroke

Geographic Reach
2 countries

177 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 16, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 20, 2017

Completed
7 months until next milestone

Study Start

First participant enrolled

January 19, 2018

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 31, 2023

Completed
17 days until next milestone

Study Completion

Last participant's last visit for all outcomes

April 17, 2023

Completed
2 years until next milestone

Results Posted

Study results publicly available

April 9, 2025

Completed
Last Updated

April 9, 2025

Status Verified

April 1, 2025

Enrollment Period

5.2 years

First QC Date

June 16, 2017

Results QC Date

April 16, 2024

Last Update Submit

April 8, 2025

Conditions

Keywords

Atrial CardiopathyCryptogenic strokeIschemic strokeApixabanAspirin

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Recurrent Stroke of Any Type

    Participants were monitored for up to 5 years of study participation. This is the number of participants who had recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type).

    Up to 5 years of study participation.

Secondary Outcomes (5)

  • Number of Participants With Recurrent Ischemic Stroke or Systemic Embolism

    Up to 5 years of study participation.

  • Number of Participants With Recurrent Stroke of Any Type or Death From Any Cause

    Up to 5 years of study participation.

  • Number of Participants With Symptomatic Intracranial Hemorrhage (Including Symptomatic Hemorrhagic Transformation of an Ischemic Stroke)

    Through 30 days after permanent discontinuation of the study drug, a duration of up to 5 years for each participant.

  • Number of Participants With Major Hemorrhage Other Than Intracranial Hemorrhage.

    Through 30 days after permanent discontinuation of the study drug, a duration of up to 5 years for each participant.

  • Number of Participant Deaths From Any Cause Number of Participants With All-cause Mortality.

    Through 30 days after permanent discontinuation of the study drug, a duration of up to 5 years for each participant.

Study Arms (2)

Active agent: Apixaban

EXPERIMENTAL

Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban

Drug: Apixaban

Active control: Aspirin

ACTIVE COMPARATOR

Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin

Drug: Aspirin

Interventions

5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).

Also known as: Eliquis
Active agent: Apixaban

Aspirin 81 mg by mouth once daily.

Also known as: Aspirin Tablet
Active control: Aspirin

Eligibility Criteria

Age45 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 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.

You may not qualify if:

  • 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.
  • 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.
  • Atrial cardiopathy is defined as ≥1 of the following:
  • PTFV1 \>5,000 μV\*ms on 12-lead ECG (ECG criterion).
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (177)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

University of South Alabama University Hospital

Mobile, Alabama, 36604, United States

Location

Chandler Regional Medical Center Chandler, AZ

Chandler, Arizona, 85224, United States

Location

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

Banner University Medical Center - Tucson

Tucson, Arizona, 85724, United States

Location

Mercy San Juan Medical Center (Dignity Health)

Carmichael, California, 95608, United States

Location

Eden Medical Center

Castro Valley, California, 94546, United States

Location

Rancho Los Amigos National Rehabilitation Center

Downey, California, 90242, United States

Location

Fountain Valley Regional Hospital and Medical Center

Fountain Valley, California, 92708, United States

Location

Community Regional Medical Center

Fresno, California, 93721, United States

Location

UCSD Health La Jolla

La Jolla, California, 92037, United States

Location

Sharp Grossmont Hospital

La Mesa, California, 92123, United States

Location

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

Los Alamitos Medical Center

Los Alamitos, California, 90720, United States

Location

Kaiser Permanente

Los Angeles, California, 90027, United States

Location

Keck Hospital Of USC

Los Angeles, California, 90033, United States

Location

Los Angeles County- USC Medical Center

Los Angeles, California, 90033, United States

Location

VA Greater Los Angeles - West LA VA Medical Center

Los Angeles, California, 90073, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Sutter Medical Center

Sacramento, California, 95816, United States

Location

Salinas Valley Memorial Hospital

Salinas, California, 93901, United States

Location

Scripps Mercy

San Diego, California, 91910, United States

Location

UCSD Medical Center - Hillcrest Hospital

San Diego, California, 92103, United States

Location

Kaiser Permanent San Diego Medical Center

San Diego, California, 92123, United States

Location

Sharp Memorial Hospital

San Diego, California, 92123, United States

Location

San Francisco General

San Francisco, California, 94110, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Good Samaritan

San Jose, California, 95124, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Swedish Medical Center

Englewood, Colorado, 80113, United States

Location

St. Mary's Medical Center

Grand Junction, Colorado, 81501, United States

Location

St. Vincent's Medical Center

Bridgeport, Connecticut, 06606, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102-5037, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06520, United States

Location

Christiana Hospital

Newark, Delaware, 19718, United States

Location

Med-star Georgetown Univ.

Washington D.C., District of Columbia, 20007, United States

Location

Medstar Washington

Washington D.C., District of Columbia, 20010, United States

Location

Boca Raton Regional Hospital

Boca Raton, Florida, 33486, United States

Location

UF Health Shands

Gainesville, Florida, 32610, United States

Location

Baptist Medical Center Jacksonville

Jacksonville, Florida, 32207, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Jackson Memorial

Miami, Florida, 33136, United States

Location

Univ. Miami Hospital

Miami, Florida, 33136, United States

Location

Baptist Hospital of Miami

Miami, Florida, 33176, United States

Location

Intercoastal Medical Group - Hyde Park

Sarasota, Florida, 34239, United States

Location

Tampa General

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Grady Memorial

Atlanta, Georgia, 30303, United States

Location

The Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Southern Illinois University Memorial Medical Center

Springfield, Illinois, 62702, United States

Location

St. John's Hospital (Prairie Research)

Springfield, Illinois, 62769, United States

Location

Central DuPage Hospital

Winfield, Illinois, 60190, United States

Location

Multi-Specialty - Methodist Plaza/Unity Point

Des Moines, Iowa, 50309, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Kansas City, Kansas, 66160, United States

Location

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical

Boston, Massachusetts, 02215, United States

Location

Brigham & Womens Hospital

Boston, Massachusetts, 20115, United States

Location

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

Location

U Mass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

University of Michigan University Hospital

Ann Arbor, Michigan, 48109, United States

Location

VA Ann Arbor Healthcare System

Ann Arbor, Michigan, 48109, United States

Location

Detroit Receiving Hospital

Detroit, Michigan, 48201, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

McLaren Flint

Flint, Michigan, 48532, United States

Location

Mercy Health St. Mary's

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49503, United States

Location

McLaren Macomb, Mount Clemens, MI

Mount Clemens, Michigan, 48043, United States

Location

McLaren Northern Michigan

Petoskey, Michigan, 49770, United States

Location

Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

Location

Hennepin County

Minneapolis, Minnesota, 55415, United States

Location

Univ. of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Regions Hospital, St. Paul

Saint Paul, Minnesota, 55101, United States

Location

United Hospital

Saint Paul, Minnesota, 55102, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Saint Luke's Hospital of Kansas City

Kansas City, Missouri, 64111, United States

Location

Cox Medical Center South

Springfield, Missouri, 65807, United States

Location

St. Louis University Hospital

St Louis, Missouri, 63104, United States

Location

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

CHI Health Immanuel

Omaha, Nebraska, 68124, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Cooper University Hospital,

Camden, New Jersey, 08103, United States

Location

Robert Wood Johnson

New Brunswick, New Jersey, 08901, United States

Location

Capital Health Medical Center Hopewell

Pennington, New Jersey, 08534, United States

Location

Univ. New Mexico

Albuquerque, New Mexico, 87131, United States

Location

Kings County Hospital

Brooklyn, New York, 11203, United States

Location

New York Presbyterian - Brooklyn Methodist Hospital

Brooklyn, New York, 11215-3609, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

NYU Langone Hospital - Brooklyn

Brooklyn, New York, 11220, United States

Location

Mount Sinai Beth Israel Brooklyn

Brooklyn, New York, 11234, United States

Location

Buffalo General Medical Center

Buffalo, New York, 14203, United States

Location

North Shore University Hospital

Manhasset, New York, 11042, United States

Location

NYU Langone

New York, New York, 10003, United States

Location

Mount Sinai West

New York, New York, 10019, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

Strong Memorial Hospital

Rochester, New York, 14642, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Moses H. Cone Memorial Hospital

Greensboro, North Carolina, 27405, United States

Location

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Sanford Medical Center Fargo

Fargo, North Dakota, 58122, United States

Location

Akron General Medical Center

Akron, Ohio, 44307, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Louis Stokes VA Medical Center

Cleveland, Ohio, 44106, United States

Location

UH Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

OSU Wexner

Columbus, Ohio, 43210, United States

Location

Ohio Health Riverside - Riverside Methodist Hospital

Columbus, Ohio, 43214, United States

Location

Miami Valley Hospita

Dayton, Ohio, 45409, United States

Location

Mercy St Vincent Medical Center

Toledo, Ohio, 43608, United States

Location

OU Medical Center Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel

Portland, Oregon, 97227, United States

Location

Oregon Health and Sciences

Portland, Oregon, 97239, United States

Location

Lehigh Valley Hospital

Allentown, Pennsylvania, 18103, United States

Location

UPMC Altoona

Altoona, Pennsylvania, 16601, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17602, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health Richland Hospital (formerly Palmetto Health)

Columbia, South Carolina, 29203, United States

Location

Prisma Health Greenville Memorial Hospital

Greenville, South Carolina, 29605, United States

Location

Methodist University Hospital

Memphis, Tennessee, 38104, United States

Location

Vanderbilt

Nashville, Tennessee, 37212, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Valley Bapist

Harlingen, Texas, 78550, United States

Location

Baylor College College of Medicine

Houston, Texas, 77030, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

Location

Univ of Texas Health Science Center San Antonio

San Antonio, Texas, 78229, United States

Location

Scott & White Memorial Hospital - Temple

Temple, Texas, 76508, United States

Location

Memorial Hermann The Woodlands Hospital

The Woodlands, Texas, 77380, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

Utah Valley Regional Medical Center

Provo, Utah, 84604, United States

Location

Univ of Utah

Salt Lake City, Utah, 84132, United States

Location

George E Whalen VA

Salt Lake City, Utah, 84148, United States

Location

UVA Medical Center

Charlottesville, Virginia, 22908, United States

Location

Bon Secours St. Mary's Hospital

Richmond, Virginia, 23226, United States

Location

Providence St. Peter Hospital

Olympia, Washington, 98506, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Puget Sound VA

Seattle, Washington, 98108, United States

Location

Swedish Medical Center - Cherry Hill Campus

Seattle, Washington, 98122, United States

Location

WVU Healthcare Ruby Memorial

Morgantown, West Virginia, 26506-9180, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

University of Calgary - Foothills Medical Centre

Calgary, Alberta, T2N2T9, Canada

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2G3, Canada

Location

Neurologic Research Center

Lethbridge, Alberta, T1J 0N9, Canada

Location

Kelowna General Hospital

Kelowna, British Columbia, V1Y 1T2, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Brandon Regional Health Center

Brandon, Manitoba, R7A 2B3, Canada

Location

Hamilton General Hospital

Hamilton, Ontario, L8L2X2, Canada

Location

Kingston General Hospital

Kingston, Ontario, K7L2V7, Canada

Location

London Health Sciences Center

London, Ontario, N6A 5A5, Canada

Location

Sunnybrook Health Sciences Center

Toronto, Ontario, M4N 3M5, Canada

Location

Enfant-Jesus Hospital

Québec, Quebec, G1J 1Z4-65543, Canada

Location

Royal University Hospital

Saskatoon, Saskatchewan, S7N0W8, Canada

Location

Related Publications (13)

  • Kamel H, Okin PM, Elkind MS, Iadecola C. Atrial Fibrillation and Mechanisms of Stroke: Time for a New Model. Stroke. 2016 Mar;47(3):895-900. doi: 10.1161/STROKEAHA.115.012004. Epub 2016 Jan 19. No abstract available.

    PMID: 26786114BACKGROUND
  • Yaghi S, Kamel H, Elkind MS. Potential new uses of non-vitamin K antagonist oral anticoagulants to treat and prevent stroke. Neurology. 2015 Sep 22;85(12):1078-84. doi: 10.1212/WNL.0000000000001817. Epub 2015 Jul 17.

    PMID: 26187229BACKGROUND
  • Kamel H, Okin PM, Longstreth WT Jr, Elkind MS, Soliman EZ. Atrial cardiopathy: a broadened concept of left atrial thromboembolism beyond atrial fibrillation. Future Cardiol. 2015 May;11(3):323-31. doi: 10.2217/fca.15.22.

    PMID: 26021638BACKGROUND
  • Yaghi S, Moon YP, Mora-McLaughlin C, Willey JZ, Cheung K, Di Tullio MR, Homma S, Kamel H, Sacco RL, Elkind MS. Left atrial enlargement and stroke recurrence: the Northern Manhattan Stroke Study. Stroke. 2015 Jun;46(6):1488-93. doi: 10.1161/STROKEAHA.115.008711. Epub 2015 Apr 23.

    PMID: 25908460BACKGROUND
  • Longstreth WT Jr, Kronmal RA, Thompson JL, Christenson RH, Levine SR, Gross R, Brey RL, Buchsbaum R, Elkind MS, Tirschwell DL, Seliger SL, Mohr JP, deFilippi CR. Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke. 2013 Mar;44(3):714-9. doi: 10.1161/STROKEAHA.112.675942. Epub 2013 Jan 22.

    PMID: 23339958BACKGROUND
  • Marshall RS, Lal BK, Edwards LJ, Huston J, Meschia JF, Brott TG, Howard G, Mena-Hurtado CI, Heck D, Sangha N, Lanzino G, Kashyap VS, Aronow HD, Sharafuddin M, Rai P, Jumani S, Voeks JH, Zhang Y, Slane KJ, Lazar RM, Liebeskind DS; CREST-H investigators. Relationship Between of Degree of Stenosis and Time-To-Peak Delay in High Grade Asymptomatic Carotid Artery Disease. Stroke. 2026 Jan 29. doi: 10.1161/STROKEAHA.125.054149. Online ahead of print.

  • Lazar RM, Howard G, Brewer MT, Cassarly C, Pauls Q, Kemp S, Tirschwell DL, Sheth KN, Wintermark M, Kamel H, Longstreth WT Jr, Elkind MSV, Broderick JP, Lansberg MG. Apixaban Versus Aspirin to Reduce Cognitive Decline After Cryptogenic Stroke and Atrial Cardiopathy: ARCADIA-Cognition Study. J Am Heart Assoc. 2025 Sep 16;14(18):e042147. doi: 10.1161/JAHA.125.042147. Epub 2025 Aug 22.

  • Elias A, Teraoka JT, Soliman EZ, Elkind MSV, Kamel H, Kronmal RA, Longstreth WT Jr, Tirschwell DL, Di Tullio MR, Marcus GM. Premature Atrial Contractions as a Marker of Atrial Cardiopathy: A Revised Analysis of the ARCADIA Randomized Trial. J Cardiovasc Electrophysiol. 2025 Jul;36(7):1487-1493. doi: 10.1111/jce.16629. Epub 2025 Apr 28.

  • Navi BB, Elkind MSV, Zhang C, Tirschwell DL, Kronmal RA, Elm J, Broderick JP, Gladstone DJ, Beyeler M, Kamel H, Longstreth WT Jr. History of Cancer and Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Clinical Trial. J Am Heart Assoc. 2025 May 6;14(9):e040543. doi: 10.1161/JAHA.124.040543. Epub 2025 Apr 23.

  • Lansberg MG, Wintermark M, Chen H, Howard G, Cassarly C, Pauls Q, Kemp S, Harris TL, Krishnaiah B, Stanton RJ, Lyerly MJ, Miller BR, Smith EE, Tirschwell DL, Sheth KN, Kamel H, Longstreth WT Jr, Elkind MSV, Broderick JP, Lazar RM. Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy: A Secondary Analysis of the ARCADIA Randomized Clinical Trial. JAMA Neurol. 2025 Mar 1;82(3):220-227. doi: 10.1001/jamaneurol.2024.4838.

  • Navi BB, Zhang C, Miller BR, Pawar A, Cushman M, Kasner SE, Tirschwell D, Longstreth WT, Kronmal R, Elm J, Zweifler RM, Tarsia J, Broderick JP, Gladstone DJ, Beyeler M, Kamel H, Elkind MSV, Streib C. Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial. Neurology. 2024 Nov 26;103(10):e210027. doi: 10.1212/WNL.0000000000210027. Epub 2024 Oct 31.

  • Navi BB, Zhang C, Miller B, Cushman M, Kasner SE, Elkind MSV, Tirschwell DL, Longstreth WT Jr, Kronmal RA, Beyeler M, Elm J, Zweifler RM, Tarsia J, Cereda CW, Bianco G, Costamagna G, Michel P, Broderick JP, Gladstone DJ, Kamel H, Streib C. Apixaban vs Aspirin in Patients With Cancer and Cryptogenic Stroke: A Post Hoc Analysis of the ARCADIA Randomized Clinical Trial. JAMA Neurol. 2024 Sep 1;81(9):958-965. doi: 10.1001/jamaneurol.2024.2404.

  • Kamel H, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Marshall RS, Broderick JP, Aragon Garcia R, Plummer P, Sabagha N, Pauls Q, Cassarly C, Dillon CR, Di Tullio MR, Hod EA, Soliman EZ, Gladstone DJ, Healey JS, Sharma M, Chaturvedi S, Janis LS, Krishnaiah B, Nahab F, Kasner SE, Stanton RJ, Kleindorfer DO, Starr M, Winder TR, Clark WM, Miller BR, Elkind MSV; ARCADIA Investigators. Apixaban to Prevent Recurrence After Cryptogenic Stroke in Patients With Atrial Cardiopathy: The ARCADIA Randomized Clinical Trial. JAMA. 2024 Feb 20;331(7):573-581. doi: 10.1001/jama.2023.27188.

Related Links

MeSH Terms

Conditions

StrokeIschemic Stroke

Interventions

apixabanAspirin

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

SalicylatesHydroxybenzoatesPhenolsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic Chemicals

Results Point of Contact

Title
Mitchell S.V. Elkind, MD, MS, FAHA/ Randolph S. Marshall, MD, MS (trial investigators)
Organization
Columbia University

Study Officials

  • Randolph S Marshall, MD

    Columbia University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
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.
Purpose
PREVENTION
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Elisabeth K Harris Professor of Neurology Chief, Stroke Division

Study Record Dates

First Submitted

June 16, 2017

First Posted

June 20, 2017

Study Start

January 19, 2018

Primary Completion

March 31, 2023

Study Completion

April 17, 2023

Last Updated

April 9, 2025

Results First Posted

April 9, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will share

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

Shared Documents
STUDY PROTOCOL
Time Frame
As per NIH/NINDS requirements.
Access Criteria
All items required by NIH/NINDS will be publicly shared.

Locations