StrokePhase 3ARCADIANCT03192215
AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
A Phase 3 study testing Apixaban and Aspirin in people with Stroke, run by Columbia University at 177 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Apixaban and Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,015 participants
- Where
- 177 sitesin 2 countries
- Study dates
- 19 Jan 2018to 17 Apr 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- To be eligible for randomization, consented participants must meet criteria for atrial cardiopathy in addition to the inclusion/exclusion criteria above.
- Atrial cardiopathy is defined as ≥1 of the following:
- PTFV1 >5,000 μV*ms on 12-lead ECG (ECG criterion).
- Serum NT-proBNP >250 pg/mL (NT-proBNP criterion).
- Left atrial diameter index ≥3 cm/m2 on echocardiogram (i.e., severe left atrial enlargement) (ECHO criterion)
Trial locations and contacts
177 sites in 2 countries.
177 sites in 2 countries
United States165 sites
Akron General Medical Center
Akron, Ohio, 44307
Univ. New Mexico
Albuquerque, New Mexico, 87131
Lehigh Valley Hospital
Allentown, Pennsylvania, 18103
UPMC Altoona
Altoona, Pennsylvania, 16601
University of Michigan University Hospital
Ann Arbor, Michigan, 48109
VA Ann Arbor Healthcare System
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30303
Grady Memorial
Atlanta, Georgia, 30303
University of Maryland Medical Center
Baltimore, Maryland, 21201
Eastern Maine Medical Center
Bangor, Maine, 04401
University of Alabama
Birmingham, Alabama, 35233
Boca Raton Regional Hospital
Boca Raton, Florida, 33486
Tufts Medical Center
Boston, Massachusetts, 02111
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Beth Israel Deaconess Medical
Boston, Massachusetts, 02215
Brigham & Womens Hospital
Boston, Massachusetts, 20115
St. Vincent's Medical Center
Bridgeport, Connecticut, 06606
Kings County Hospital
Brooklyn, New York, 11203
New York Presbyterian - Brooklyn Methodist Hospital
Brooklyn, New York, 11215-3609
Maimonides Medical Center
Brooklyn, New York, 11219
NYU Langone Hospital - Brooklyn
Brooklyn, New York, 11220
Mount Sinai Beth Israel Brooklyn
Brooklyn, New York, 11234
Buffalo General Medical Center
Buffalo, New York, 14203
Lahey Hospital & Medical Center
Burlington, Massachusetts, 01805
Cooper University Hospital,
Camden, New Jersey, 08103
Mercy San Juan Medical Center (Dignity Health)
Carmichael, California, 95608
Eden Medical Center
Castro Valley, California, 94546
Chandler Regional Medical Center Chandler, AZ
Chandler, Arizona, 85224
Medical University of South Carolina
Charleston, South Carolina, 29425
UVA Medical Center
Charlottesville, Virginia, 22908
Northwestern Memorial Hospital
Chicago, Illinois, 60611
Rush University
Chicago, Illinois, 60612
University of Illinois
Chicago, Illinois, 60612
University of Chicago Medical Center
Chicago, Illinois, 60637
University of Cincinnati
Cincinnati, Ohio, 45219
Louis Stokes VA Medical Center
Cleveland, Ohio, 44106
UH Cleveland Medical Center
Cleveland, Ohio, 44106
MetroHealth Medical Center
Cleveland, Ohio, 44109
Cleveland Clinic
Cleveland, Ohio, 44195
Prisma Health Richland Hospital (formerly Palmetto Health)
Columbia, South Carolina, 29203
OSU Wexner
Columbus, Ohio, 43210
Ohio Health Riverside - Riverside Methodist Hospital
Columbus, Ohio, 43214
UT Southwestern Medical Center
Dallas, Texas, 75390
Miami Valley Hospita
Dayton, Ohio, 45409
Multi-Specialty - Methodist Plaza/Unity Point
Des Moines, Iowa, 50309
Detroit Receiving Hospital
Detroit, Michigan, 48201
Henry Ford Hospital
Detroit, Michigan, 48202
Rancho Los Amigos National Rehabilitation Center
Downey, California, 90242
Swedish Medical Center
Englewood, Colorado, 80113
Sanford Medical Center Fargo
Fargo, North Dakota, 58122
McLaren Flint
Flint, Michigan, 48532
Fountain Valley Regional Hospital and Medical Center
Fountain Valley, California, 92708
Community Regional Medical Center
Fresno, California, 93721
UF Health Shands
Gainesville, Florida, 32610
St. Mary's Medical Center
Grand Junction, Colorado, 81501
Mercy Health St. Mary's
Grand Rapids, Michigan, 49503
Spectrum Health
Grand Rapids, Michigan, 49503
Moses H. Cone Memorial Hospital
Greensboro, North Carolina, 27405
Prisma Health Greenville Memorial Hospital
Greenville, South Carolina, 29605
Valley Bapist
Harlingen, Texas, 78550
Hartford Hospital
Hartford, Connecticut, 06102-5037
The Queen's Medical Center
Honolulu, Hawaii, 96813
Baylor College College of Medicine
Houston, Texas, 77030
Houston Methodist Hospital
Houston, Texas, 77030
Memorial Hermann Texas Medical Center
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Baptist Medical Center Jacksonville
Jacksonville, Florida, 32207
Mayo Clinic
Jacksonville, Florida, 32224
University of Kansas
Kansas City, Kansas, 66160
Saint Luke's Hospital of Kansas City
Kansas City, Missouri, 64111
UCSD Health La Jolla
La Jolla, California, 92037
Sharp Grossmont Hospital
La Mesa, California, 92123
Lancaster General Hospital
Lancaster, Pennsylvania, 17602
Baptist Health Lexington
Lexington, Kentucky, 40503
University of Kentucky
Lexington, Kentucky, 40536
Long Beach Memorial Medical Center
Long Beach, California, 90806
Los Alamitos Medical Center
Los Alamitos, California, 90720
Kaiser Permanente
Los Angeles, California, 90027
Keck Hospital Of USC
Los Angeles, California, 90033
Los Angeles County- USC Medical Center
Los Angeles, California, 90033
VA Greater Los Angeles - West LA VA Medical Center
Los Angeles, California, 90073
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095
University of Louisville Hospital
Louisville, Kentucky, 40202
University of Wisconsin
Madison, Wisconsin, 53792
North Shore University Hospital
Manhasset, New York, 11042
Methodist University Hospital
Memphis, Tennessee, 38104
Jackson Memorial
Miami, Florida, 33136
Univ. Miami Hospital
Miami, Florida, 33136
Baptist Hospital of Miami
Miami, Florida, 33176
Froedtert Hospital
Milwaukee, Wisconsin, 53226
Abbott Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County
Minneapolis, Minnesota, 55415
Univ. of Minnesota
Minneapolis, Minnesota, 55455
University of South Alabama University Hospital
Mobile, Alabama, 36604
WVU Healthcare Ruby Memorial
Morgantown, West Virginia, 26506-9180
McLaren Macomb, Mount Clemens, MI
Mount Clemens, Michigan, 48043
Intermountain Medical Center
Murray, Utah, 84107
Vanderbilt
Nashville, Tennessee, 37212
Robert Wood Johnson
New Brunswick, New Jersey, 08901
Yale New Haven Hospital
New Haven, Connecticut, 06520
Ochsner Medical Center
New Orleans, Louisiana, 70121
NYU Langone
New York, New York, 10003
Mount Sinai West
New York, New York, 10019
Columbia University Medical Center
New York, New York, 10032
Weill Cornell Medicine
New York, New York, 10065
Lenox Hill Hospital
New York, New York, 10075
Christiana Hospital
Newark, Delaware, 19718
OU Medical Center Oklahoma
Oklahoma City, Oklahoma, 73104
Providence St. Peter Hospital
Olympia, Washington, 98506
CHI Health Immanuel
Omaha, Nebraska, 68124
University of Nebraska
Omaha, Nebraska, 68198
UC Irvine Medical Center
Orange, California, 92868
Capital Health Medical Center Hopewell
Pennington, New Jersey, 08534
OSF St. Francis Medical Center
Peoria, Illinois, 61637
McLaren Northern Michigan
Petoskey, Michigan, 49770
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Temple University
Philadelphia, Pennsylvania, 19140
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
UPMC Presbyterian
Pittsburgh, Pennsylvania, 15213
Legacy Emanuel
Portland, Oregon, 97227
Oregon Health and Sciences
Portland, Oregon, 97239
Rhode Island Hospital
Providence, Rhode Island, 02903
Utah Valley Regional Medical Center
Provo, Utah, 84604
Bon Secours St. Mary's Hospital
Richmond, Virginia, 23226
Mayo Clinic
Rochester, Minnesota, 55905
Strong Memorial Hospital
Rochester, New York, 14642
Sutter Medical Center
Sacramento, California, 95816
Regions Hospital, St. Paul
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Salinas Valley Memorial Hospital
Salinas, California, 93901
Univ of Utah
Salt Lake City, Utah, 84132
George E Whalen VA
Salt Lake City, Utah, 84148
Univ of Texas Health Science Center San Antonio
San Antonio, Texas, 78229
Scripps Mercy
San Diego, California, 91910
UCSD Medical Center - Hillcrest Hospital
San Diego, California, 92103
Kaiser Permanent San Diego Medical Center
San Diego, California, 92123
Sharp Memorial Hospital
San Diego, California, 92123
San Francisco General
San Francisco, California, 94110
UCSF Medical Center
San Francisco, California, 94143
Good Samaritan
San Jose, California, 95124
Intercoastal Medical Group - Hyde Park
Sarasota, Florida, 34239
Harborview Medical Center
Seattle, Washington, 98104
Puget Sound VA
Seattle, Washington, 98108
Swedish Medical Center - Cherry Hill Campus
Seattle, Washington, 98122
Southern Illinois University Memorial Medical Center
Springfield, Illinois, 62702
St. John's Hospital (Prairie Research)
Springfield, Illinois, 62769
Cox Medical Center South
Springfield, Missouri, 65807
St. Louis University Hospital
St Louis, Missouri, 63104
Barnes Jewish Hospital
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305
Tampa General
Tampa, Florida, 33606
Scott & White Memorial Hospital - Temple
Temple, Texas, 76508
Montefiore Medical Center
The Bronx, New York, 10467
Memorial Hermann The Woodlands Hospital
The Woodlands, Texas, 77380
Mercy St Vincent Medical Center
Toledo, Ohio, 43608
Banner University Medical Center - Tucson
Tucson, Arizona, 85724
Med-star Georgetown Univ.
Washington D.C., District of Columbia, 20007
Medstar Washington
Washington D.C., District of Columbia, 20010
Central DuPage Hospital
Winfield, Illinois, 60190
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
U Mass Memorial Medical Center
Worcester, Massachusetts, 01655
Canada12 sites
Brandon Regional Health Center
Brandon, Manitoba, R7A 2B3
University of Calgary - Foothills Medical Centre
Calgary, Alberta, T2N2T9
University of Alberta Hospital
Edmonton, Alberta, T6G 2G3
Hamilton General Hospital
Hamilton, Ontario, L8L2X2
Kelowna General Hospital
Kelowna, British Columbia, V1Y 1T2
Kingston General Hospital
Kingston, Ontario, K7L2V7
Neurologic Research Center
Lethbridge, Alberta, T1J 0N9
London Health Sciences Center
London, Ontario, N6A 5A5
Enfant-Jesus Hospital
Québec, Quebec, G1J 1Z4-65543
Royal University Hospital
Saskatoon, Saskatchewan, S7N0W8
Sunnybrook Health Sciences Center
Toronto, Ontario, M4N 3M5
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
About this study
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.
Read the 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.
- Conditions
- Stroke
- Keywords
- Atrial Cardiopathy, Cryptogenic stroke, Ischemic stroke, Apixaban, Aspirin
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
AspirinDrug
Also called Aspirin Tablet
Aspirin 81 mg by mouth once daily.
| Study group | Role | What they receive |
|---|---|---|
| Active agent: Apixaban | Experimental | Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban Receives: 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 Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 5 years of study participation.
Secondary outcomes (5)
Number of Participants With Recurrent Ischemic Stroke or Systemic Embolism
Secondary efficacy outcome A. Participants were monitored for up to 5 years. This is the number of participants who had recurrent ischemic stroke or systemic embolism during the time of observation.
Measured: Up to 5 years of study participation.
Number of Participants With Recurrent Stroke of Any Type or Death From Any Cause
Secondary efficacy outcome B. Participants were monitored for up to 5 years. This is the number of participants who had recurrent stroke of any type or death from any cause during the observation time.
Measured: Up to 5 years of study participation.
Number of Participants With Symptomatic Intracranial Hemorrhage (Including Symptomatic Hemorrhagic Transformation of an Ischemic Stroke)
Primary safety outcome A. This is the number of participants who had symptomatic intracranial hemorrhage from any cause during the time of observation. Symptomatic intracranial hemorrhage includes symptomatic hemorrhagic transformation of ischemic stroke, which required new symptoms or signs adjudicated as being due to the hemorrhagic transformation or a patient whose initial imaging was judged to include hemorrhagic transformation of an ischemic stroke.
Measured: 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.
This is the number of participants who had major hemorrhage other than intracranial hemorrhage.
Measured: 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.
Secondary safety outcome. This is the number of participants who had all-cause mortality during time of observation.
Measured: Through 30 days after permanent discontinuation of the study drug, a duration of up to 5 years for each participant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2017
- Study start19 Jan 2018
- Primary completion31 Mar 2023
- Study completion17 Apr 2023
Why it stopped: The DSMB halted the trial prematurely due to futility without any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (13)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,015 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Randolph S. Marshall, MD, Columbia University
- Investigators
- Randolph S Marshall, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03192215
- Sponsor's protocol ID
- AAAR4607
- Other IDs
- 1U01NS095869-01A1
- Acronym
- ARCADIA
- Status last verified
- Apr 2025
- First submitted
- 16 Jun 2017
- Last updated
- 9 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: To share individual participant data (IPD) of baseline characteristics, follow up, outcomes, etc. based on NIH/NINDS requirements.
Publications
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.
PubMed 26786114Yaghi 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.
PubMed 26187229Kamel 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.
PubMed 26021638Yaghi 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.
PubMed 25908460Longstreth 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.
PubMed 23339958Ridha M, Hailat R, Stanton R, Merkler AE, Elkind MSV, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Hannawi Y, Kamel H, Burke J, Woo D. Hypertension With High-Risk Features in Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Clinical Trial. JAMA Neurol. 2026 Jun 1;83(6):573-581. doi: 10.1001/jamaneurol.2026.0855.
PubMed 42008258Lazar 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.
PubMed 40847528Elias 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.
PubMed 40294164Navi 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.
PubMed 40265582Lansberg 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.
PubMed 39869342Navi 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.
PubMed 39481070Navi 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.
PubMed 39133474Kamel 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.
PubMed 38324415
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
- ClinicalTrials.gov ID
- NCT03192215
- Acronym / sponsor ID
- ARCADIA / AAAR4607
- Conditions
- Stroke
- Keywords
- Atrial Cardiopathy, Cryptogenic stroke, Ischemic stroke, Apixaban, Aspirin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The DSMB halted the trial prematurely due to futility without any safety concerns.
- Enrolment
- 1,015 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- 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
- Study start
- 19 Jan 2018 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 17 Apr 2023 (actual)
- First posted
- 20 Jun 2017 (actual)
- Results
- Posted 9 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active agent: Apixaban | Experimental | Drug: ApixabanPatients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban |
| Active control: Aspirin | Active comparator | Drug: AspirinPatients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: Eliquis5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose). | Drug | Active agent: Apixaban |
| AspirinAlso: Aspirin TabletAspirin 81 mg by mouth once daily. | Drug | Active control: Aspirin |
Primary outcome
Number of Participants With Recurrent Stroke of Any Type
Time frame: Up to 5 years of study participation.
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).
5 secondary outcomes
Number of Participants With Recurrent Ischemic Stroke or Systemic Embolism
Time frame: Up to 5 years of study participation.
Number of Participants With Recurrent Stroke of Any Type or Death From Any Cause
Time frame: Up to 5 years of study participation.
Number of Participants With Symptomatic Intracranial Hemorrhage (Including Symptomatic Hemorrhagic Transformation of an Ischemic Stroke)
Time frame: 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.
Time frame: 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.
Time frame: Through 30 days after permanent discontinuation of the study drug, a duration of up to 5 years for each participant.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 26786114Kamel 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.
- Background: PubMed 26187229Yaghi 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.
- Background: PubMed 26021638Kamel 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.
- Background: PubMed 25908460Yaghi 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.
- Background: PubMed 23339958Longstreth 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.
- Derived from this study: PubMed 42008258Ridha M, Hailat R, Stanton R, Merkler AE, Elkind MSV, Longstreth WT Jr, Tirschwell DL, Kronmal RA, Hannawi Y, Kamel H, Burke J, Woo D. Hypertension With High-Risk Features in Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Clinical Trial. JAMA Neurol. 2026 Jun 1;83(6):573-581. doi: 10.1001/jamaneurol.2026.0855.
- Derived from this study: PubMed 40847528Lazar 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.
- Derived from this study: PubMed 40294164Elias 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.
- Derived from this study: PubMed 40265582Navi 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.
- Derived from this study: PubMed 39869342Lansberg 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.
- Derived from this study: PubMed 39481070Navi 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.
- Derived from this study: PubMed 39133474Navi 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.
- NIH/NINDS StrokeNet Prevention trials websiteLink provided by the sponsor.
- ARCADIA Trial VideoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. To share individual participant data (IPD) of baseline characteristics, follow up, outcomes, etc. based on NIH/NINDS requirements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randolph S Marshall, MD principal investigator
Columbia University
177 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban and Aspirin in people with Stroke, run by Columbia University at 177 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 177 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Recurrent Stroke of Any Type (time frame: Up to 5 years of study participation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03192215, which also lists 13 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.