AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke

Stroke Clinical Trial

— ARCADIA  

Official title:

AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03192215
• Other study ID #: AAAR4607
• Secondary ID: 1U01NS095869-01A
• Status: Terminated
• Phase: Phase 3
• Start date: January 19, 2018
• Est. completion date: April 17, 2023

Study information

• Verified date: June 2023
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

• Secondary: To test the hypothesis that the relative efficacy of apixaban over aspirin increases with the severity of atrial cardiopathy.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1015
• Est. completion date: April 17, 2023
• Est. primary completion date: March 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Diseases
• Ischemic Stroke
• Stroke

Intervention

Drug:
• Apixaban
5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
• Aspirin
Aspirin 81 mg by mouth once daily.

Locations

Country	Name	City	State
Canada	Brandon Regional Health Center	Brandon	Manitoba
Canada	University of Calgary - Foothills Medical Centre	Calgary	Alberta
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Kelowna General Hospital	Kelowna	British Columbia
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Neurologic Research Center	Lethbridge	Alberta
Canada	London Health Sciences Center	London	Ontario
Canada	Enfant-Jesus Hospital	Québec	Quebec
Canada	Royal University Hospital	Saskatoon	Saskatchewan
Canada	Sunnybrook Health Sciences Center	Toronto	Ontario
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	Akron General Medical Center	Akron	Ohio
United States	Univ. New Mexico	Albuquerque	New Mexico
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	UPMC Altoona	Altoona	Pennsylvania
United States	University of Michigan University Hospital	Ann Arbor	Michigan
United States	VA Ann Arbor Healthcare System	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Grady Memorial	Atlanta	Georgia
United States	University of Maryland Medical Center	Baltimore	Maryland
United States	Eastern Maine Medical Center	Bangor	Maine
United States	University of Alabama	Birmingham	Alabama
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	Beth Israel Deaconess Medical	Boston	Massachusetts
United States	Boston Medical Center	Boston	Massachusetts
United States	Brigham & Womens Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	St. Vincent's Medical Center	Bridgeport	Connecticut
United States	Montefiore Medical Center	Bronx	New York
United States	Kings County Hospital	Brooklyn	New York
United States	Maimonides Medical Center	Brooklyn	New York
United States	Mount Sinai Beth Israel Brooklyn	Brooklyn	New York
United States	New York Presbyterian - Brooklyn Methodist Hospital	Brooklyn	New York
United States	NYU Langone Hospital - Brooklyn	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	Cooper University Hospital,	Camden	New Jersey
United States	Mercy San Juan Medical Center (Dignity Health)	Carmichael	California
United States	Eden Medical Center	Castro Valley	California
United States	Chandler Regional Medical Center Chandler, AZ	Chandler	Arizona
United States	Medical University of South Carolina	Charleston	South Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	Rush University	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	Louis Stokes VA Medical Center	Cleveland	Ohio
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	UH Cleveland Medical Center	Cleveland	Ohio
United States	Prisma Health Richland Hospital (formerly Palmetto Health)	Columbia	South Carolina
United States	Ohio Health Riverside - Riverside Methodist Hospital	Columbus	Ohio
United States	OSU Wexner	Columbus	Ohio
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Miami Valley Hospita	Dayton	Ohio
United States	Multi-Specialty - Methodist Plaza/Unity Point	Des Moines	Iowa
United States	Detroit Receiving Hospital	Detroit	Michigan
United States	Henry Ford Hospital	Detroit	Michigan
United States	Rancho Los Amigos National Rehabilitation Center	Downey	California
United States	Swedish Medical Center	Englewood	Colorado
United States	Sanford Medical Center Fargo	Fargo	North Dakota
United States	McLaren Flint	Flint	Michigan
United States	Fountain Valley Regional Hospital and Medical Center	Fountain Valley	California
United States	Community Regional Medical Center	Fresno	California
United States	UF Health Shands	Gainesville	Florida
United States	St. Mary's Medical Center	Grand Junction	Colorado
United States	Mercy Health St. Mary's	Grand Rapids	Michigan
United States	Spectrum Health	Grand Rapids	Michigan
United States	Moses H. Cone Memorial Hospital	Greensboro	North Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Valley Bapist	Harlingen	Texas
United States	Hartford Hospital	Hartford	Connecticut
United States	The Queen's Medical Center	Honolulu	Hawaii
United States	Baylor College College of Medicine	Houston	Texas
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Baptist Medical Center Jacksonville	Jacksonville	Florida
United States	Mayo Clinic	Jacksonville	Florida
United States	Saint Luke's Hospital of Kansas City	Kansas City	Missouri
United States	University of Kansas	Kansas City	Kansas
United States	UCSD Health La Jolla	La Jolla	California
United States	Sharp Grossmont Hospital	La Mesa	California
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky	Lexington	Kentucky
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Los Alamitos Medical Center	Los Alamitos	California
United States	Kaiser Permanente	Los Angeles	California
United States	Keck Hospital Of USC	Los Angeles	California
United States	Los Angeles County- USC Medical Center	Los Angeles	California
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California
United States	VA Greater Los Angeles - West LA VA Medical Center	Los Angeles	California
United States	University of Louisville Hospital	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	North Shore University Hospital	Manhasset	New York
United States	Methodist University Hospital	Memphis	Tennessee
United States	Baptist Hospital of Miami	Miami	Florida
United States	Jackson Memorial	Miami	Florida
United States	Univ. Miami Hospital	Miami	Florida
United States	Froedtert Hospital	Milwaukee	Wisconsin
United States	Abbott Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County	Minneapolis	Minnesota
United States	Univ. of Minnesota	Minneapolis	Minnesota
United States	University of South Alabama University Hospital	Mobile	Alabama
United States	WVU Healthcare Ruby Memorial	Morgantown	West Virginia
United States	McLaren Macomb, Mount Clemens, MI	Mount Clemens	Michigan
United States	Intermountain Medical Center	Murray	Utah
United States	Vanderbilt	Nashville	Tennessee
United States	Robert Wood Johnson	New Brunswick	New Jersey
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Ochsner Medical Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Lenox Hill Hospital	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYU Langone	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	OU Medical Center Oklahoma	Oklahoma City	Oklahoma
United States	Providence St. Peter Hospital	Olympia	Washington
United States	CHI Health Immanuel	Omaha	Nebraska
United States	University of Nebraska	Omaha	Nebraska
United States	UC Irvine Medical Center	Orange	California
United States	Capital Health Medical Center Hopewell	Pennington	New Jersey
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	McLaren Northern Michigan	Petoskey	Michigan
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University	Philadelphia	Pennsylvania
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Allegheny General Hospital	Pittsburgh	Pennsylvania
United States	UPMC Presbyterian	Pittsburgh	Pennsylvania
United States	Legacy Emanuel	Portland	Oregon
United States	Oregon Health and Sciences	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Utah Valley Regional Medical Center	Provo	Utah
United States	Bon Secours St. Mary's Hospital	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	Strong Memorial Hospital	Rochester	New York
United States	Sutter Medical Center	Sacramento	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	St. Louis University Hospital	Saint Louis	Missouri
United States	Regions Hospital, St. Paul	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Salinas Valley Memorial Hospital	Salinas	California
United States	George E Whalen VA	Salt Lake City	Utah
United States	Univ of Utah	Salt Lake City	Utah
United States	Univ of Texas Health Science Center San Antonio	San Antonio	Texas
United States	Kaiser Permanent San Diego Medical Center	San Diego	California
United States	Scripps Mercy	San Diego	California
United States	Sharp Memorial Hospital	San Diego	California
United States	UCSD Medical Center - Hillcrest Hospital	San Diego	California
United States	San Francisco General	San Francisco	California
United States	UCSF Medical Center	San Francisco	California
United States	Good Samaritan	San Jose	California
United States	Intercoastal Medical Group - Hyde Park	Sarasota	Florida
United States	Harborview Medical Center	Seattle	Washington
United States	Puget Sound VA	Seattle	Washington
United States	Swedish Medical Center - Cherry Hill Campus	Seattle	Washington
United States	Cox Medical Center South	Springfield	Missouri
United States	Southern Illinois University Memorial Medical Center	Springfield	Illinois
United States	St. John's Hospital (Prairie Research)	Springfield	Illinois
United States	Stanford University Medical Center	Stanford	California
United States	Tampa General	Tampa	Florida
United States	Scott & White Memorial Hospital - Temple	Temple	Texas
United States	Memorial Hermann The Woodlands Hospital	The Woodlands	Texas
United States	Mercy St Vincent Medical Center	Toledo	Ohio
United States	Banner University Medical Center - Tucson	Tucson	Arizona
United States	Med-star Georgetown Univ.	Washington	District of Columbia
United States	Medstar Washington	Washington	District of Columbia
United States	Central DuPage Hospital	Winfield	Illinois
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina
United States	U Mass Memorial Medical Center	Worcester	Massachusetts

Sponsors (9)

Lead Sponsor	Collaborator
Columbia University	Bristol-Myers Squibb, Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), Pfizer, Roche Pharma AG, University of Cincinnati, University of Washington, Weill Medical College of Cornell University

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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

External Links

•   ARCADIA Trial Video
•   NIH/NINDS StrokeNet Prevention trials website