AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
- Registration Number
- NCT03192215
- Lead Sponsor
- Columbia University
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1015
-
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.
- 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.
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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Active agent: Apixaban Apixaban Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Apixaban Active control: Aspirin Aspirin Patients with a recent embolic stroke of undetermined source (ESUS) and evidence of atrial cardiopathy will receive Aspirin
- Primary Outcome Measures
Name Time Method Number of Participants With Recurrent Stroke of Any Type 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).
- Secondary Outcome Measures
Name Time Method Number of Participants With Recurrent Ischemic Stroke or Systemic Embolism Up to 5 years of study participation. 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.
Number of Participants With Recurrent Stroke of Any Type or Death From Any Cause Up to 5 years of study participation. 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.
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. 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.
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. This is the number of participants who had major hemorrhage other than intracranial hemorrhage.
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. Secondary safety outcome. This is the number of participants who had all-cause mortality during time of observation.
Trial Locations
- Locations (176)
VA Greater Los Angeles - West LA VA Medical Center
🇺🇸Los Angeles, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Grady Memorial
🇺🇸Atlanta, Georgia, United States
Lahey Hospital & Medical Center
🇺🇸Burlington, Massachusetts, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Fountain Valley Regional Hospital and Medical Center
🇺🇸Fountain Valley, California, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Moses H. Cone Memorial Hospital
🇺🇸Greensboro, North Carolina, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Louis Stokes VA Medical Center
🇺🇸Cleveland, Ohio, United States
OSU Wexner
🇺🇸Columbus, Ohio, United States
UH Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Ohio Health Riverside - Riverside Methodist Hospital
🇺🇸Columbus, Ohio, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Kelowna General Hospital
🇨🇦Kelowna, British Columbia, Canada
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical
🇺🇸Boston, Massachusetts, United States
Brigham & Womens Hospital
🇺🇸Boston, Massachusetts, United States
Jackson Memorial
🇺🇸Miami, Florida, United States
Baptist Hospital of Miami
🇺🇸Miami, Florida, United States
Baylor College College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist Hospital
🇺🇸Houston, Texas, 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
UCSD Medical Center - Hillcrest Hospital
🇺🇸San Diego, California, United States
Kaiser Permanent San Diego Medical Center
🇺🇸San Diego, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of South Alabama University Hospital
🇺🇸Mobile, Alabama, United States
Keck Hospital Of USC
🇺🇸Los Angeles, California, United States
Scripps Mercy
🇺🇸San Diego, California, United States
Los Alamitos Medical Center
🇺🇸Los Alamitos, California, United States
Community Regional Medical Center
🇺🇸Fresno, California, United States
Univ. of Minnesota
🇺🇸Minneapolis, Minnesota, United States
McLaren Northern Michigan
🇺🇸Petoskey, Michigan, United States
Hennepin County
🇺🇸Minneapolis, Minnesota, United States
Univ. New Mexico
🇺🇸Albuquerque, New Mexico, United States
Kings County Hospital
🇺🇸Brooklyn, New York, United States
Cooper University Hospital,
🇺🇸Camden, New Jersey, United States
Methodist University Hospital
🇺🇸Memphis, Tennessee, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
WVU Healthcare Ruby Memorial
🇺🇸Morgantown, West Virginia, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
Valley Bapist
🇺🇸Harlingen, Texas, United States
Memorial Hermann The Woodlands Hospital
🇺🇸The Woodlands, Texas, United States
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Prisma Health Greenville Memorial Hospital
🇺🇸Greenville, South Carolina, United States
UPMC Presbyterian
🇺🇸Pittsburgh, Pennsylvania, United States
Scott & White Memorial Hospital - Temple
🇺🇸Temple, Texas, United States
Providence St. Peter Hospital
🇺🇸Olympia, Washington, United States
University of Calgary - Foothills Medical Centre
🇨🇦Calgary, Alberta, Canada
London Health Sciences Center
🇨🇦London, Ontario, Canada
Royal University Hospital
🇨🇦Saskatoon, Saskatchewan, Canada
Enfant-Jesus Hospital
🇨🇦Québec, Quebec, Canada
Univ of Texas Health Science Center San Antonio
🇺🇸San Antonio, Texas, United States
San Francisco General
🇺🇸San Francisco, California, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States
Univ of Utah
🇺🇸Salt Lake City, Utah, United States
George E Whalen VA
🇺🇸Salt Lake City, Utah, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
OU Medical Center Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel
🇺🇸Portland, Oregon, United States
Oregon Health and Sciences
🇺🇸Portland, Oregon, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
Tampa General
🇺🇸Tampa, Florida, United States
University of Nebraska
🇺🇸Omaha, Nebraska, United States
Froedtert Hospital
🇺🇸Milwaukee, Wisconsin, United States
Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Mercy San Juan Medical Center (Dignity Health)
🇺🇸Carmichael, California, United States
UCSD Health La Jolla
🇺🇸La Jolla, California, United States
Sharp Grossmont Hospital
🇺🇸La Mesa, California, United States
Los Angeles County- USC Medical Center
🇺🇸Los Angeles, California, United States
Kaiser Permanente
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Swedish Medical Center
🇺🇸Englewood, Colorado, United States
St. Mary's Medical Center
🇺🇸Grand Junction, Colorado, United States
St. Vincent's Medical Center
🇺🇸Bridgeport, Connecticut, United States
Christiana Hospital
🇺🇸Newark, Delaware, United States
Med-star Georgetown Univ.
🇺🇸Washington, District of Columbia, United States
Medstar Washington
🇺🇸Washington, District of Columbia, United States
Baptist Medical Center Jacksonville
🇺🇸Jacksonville, Florida, United States
Univ. Miami Hospital
🇺🇸Miami, Florida, United States
Rush University
🇺🇸Chicago, Illinois, United States
Southern Illinois University Memorial Medical Center
🇺🇸Springfield, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
St. John's Hospital (Prairie Research)
🇺🇸Springfield, Illinois, United States
Multi-Specialty - Methodist Plaza/Unity Point
🇺🇸Des Moines, Iowa, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Central DuPage Hospital
🇺🇸Winfield, Illinois, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
Eastern Maine Medical Center
🇺🇸Bangor, Maine, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
U Mass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
McLaren Flint
🇺🇸Flint, Michigan, United States
McLaren Macomb, Mount Clemens, MI
🇺🇸Mount Clemens, Michigan, United States
Mercy Health St. Mary's
🇺🇸Grand Rapids, Michigan, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Regions Hospital, St. Paul
🇺🇸Saint Paul, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Barnes Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
St. Louis University Hospital
🇺🇸Saint Louis, Missouri, United States
Cox Medical Center South
🇺🇸Springfield, Missouri, United States
Capital Health Medical Center Hopewell
🇺🇸Pennington, New Jersey, United States
Robert Wood Johnson
🇺🇸New Brunswick, New Jersey, United States
NYU Langone Hospital - Brooklyn
🇺🇸Brooklyn, New York, United States
New York Presbyterian - Brooklyn Methodist Hospital
🇺🇸Brooklyn, New York, United States
Maimonides Medical Center
🇺🇸Brooklyn, New York, United States
Mount Sinai Beth Israel Brooklyn
🇺🇸Brooklyn, New York, United States
NYU Langone
🇺🇸New York, New York, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Lenox Hill Hospital
🇺🇸New York, New York, United States
Strong Memorial Hospital
🇺🇸Rochester, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Mount Sinai West
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Miami Valley Hospita
🇺🇸Dayton, Ohio, United States
Mercy St Vincent Medical Center
🇺🇸Toledo, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
UPMC Altoona
🇺🇸Altoona, Pennsylvania, United States
UVA Medical Center
🇺🇸Charlottesville, Virginia, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Rancho Los Amigos National Rehabilitation Center
🇺🇸Downey, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Intercoastal Medical Group - Hyde Park
🇺🇸Sarasota, Florida, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
University of Kansas
🇺🇸Kansas City, Kansas, United States
Akron General Medical Center
🇺🇸Akron, Ohio, United States
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Neurologic Research Center
🇨🇦Lethbridge, Alberta, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Brandon Regional Health Center
🇨🇦Brandon, Manitoba, Canada
Hamilton General Hospital
🇨🇦Hamilton, Ontario, Canada
Chandler Regional Medical Center Chandler, AZ
🇺🇸Chandler, Arizona, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
Banner University Medical Center - Tucson
🇺🇸Tucson, Arizona, United States
Eden Medical Center
🇺🇸Castro Valley, California, United States
UC Irvine Medical Center
🇺🇸Orange, California, United States
Salinas Valley Memorial Hospital
🇺🇸Salinas, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
Good Samaritan
🇺🇸San Jose, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Sanford Medical Center Fargo
🇺🇸Fargo, North Dakota, United States
CHI Health Immanuel
🇺🇸Omaha, Nebraska, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
Prisma Health Richland Hospital (formerly Palmetto Health)
🇺🇸Columbia, South Carolina, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
The Queen's Medical Center
🇺🇸Honolulu, Hawaii, United States
Sutter Medical Center
🇺🇸Sacramento, California, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
UF Health Shands
🇺🇸Gainesville, Florida, United States
University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
Ochsner Medical Center
🇺🇸New Orleans, Louisiana, United States
Wake Forest Baptist Medical Center
🇺🇸Winston-Salem, North Carolina, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of Michigan University Hospital
🇺🇸Ann Arbor, Michigan, United States
VA Ann Arbor Healthcare System
🇺🇸Ann Arbor, Michigan, United States
Saint Luke's Hospital of Kansas City
🇺🇸Kansas City, Missouri, United States
Bon Secours St. Mary's Hospital
🇺🇸Richmond, Virginia, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States