ARCADIA: AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke

Sponsor
Columbia University (Other)
Overall Status
Recruiting
CT.gov ID
NCT03192215
Collaborator
National Institute of Neurological Disorders and Stroke (NINDS) (NIH), University of Cincinnati (Other), Medical University of South Carolina (Other), Bristol-Myers Squibb (Industry), Pfizer (Industry), Roche Pharma AG (Industry), Weill Medical College of Cornell University (Other), University of Washington (Other)
1,100
182
2
76.4
6
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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

Study Type:
Interventional
Anticipated Enrollment :
1100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Active treatment will be either apixaban 5 mg or aspirin 81 mg. An adjusted dose of apixaban 2.5 mg will be used for subjects with at least two of the following: age greater than or equal to 80 years, body weight less than or equal to 60 kg, or known serum creatinine greater than or equal to 1.5 mg/dL. There will be six possible study tablets: apixaban 5 mg (regular dose), apixaban 2.5 mg (adjusted dose), apixaban 5 mg placebo, apixaban 2.5 mg placebo, aspirin 81 mg, and aspirin placebo. All subjects will be randomized to receive active treatment with either active apixaban or active aspirin. Study treatments will be supplied in a double-dummy fashion as apixaban 5 mg (2.5 mg for the adjusted dose) or matching placebo, and aspirin 81 mg or matching placebo.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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Eligible patients will be allocated in a 1:1 ratio to apixaban or aspirin using the minimal sufficient balance randomization method to prevent serious treatment imbalances by study site.
Primary Purpose:
Prevention
Official Title:
AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
Actual Study Start Date :
Jan 19, 2018
Anticipated Primary Completion Date :
Jun 1, 2024
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Active agent: Apixaban

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

Drug: Apixaban
5 mg by mouth twice daily (2.5 mg for subjects meeting standard criteria for an adjusted dose).
Other Names:
  • Eliquis
  • Active Comparator: Active control: Aspirin

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

    Drug: Aspirin
    Aspirin 81 mg by mouth once daily.
    Other Names:
  • Aspirin Tablet
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of recurrent stroke [7 years]

      Recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type)

    Secondary Outcome Measures

    1. Incidence of recurrent ischemic stroke or systemic embolism [Up to 7 years]

      Secondary efficacy outcome A

    2. Incidence of recurrent stroke of any type plus death from any cause [Up to 7 years]

      Secondary efficacy outcome B

    3. Incidence of symptomatic intracranial hemorrhage (including symptomatic hemorrhagic transformation of an ischemic stroke). [Up to 7 years]

      Primary safety outcome A

    4. Incidence of major hemorrhage other than intracranial hemorrhage [Up to 7 years]

      Primary safety outcome B

    5. Incidence of death from any cause [Up to 7 years]

      Secondary safety outcome

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    45 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age ≥ 45 years.

    • Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.

    • Modified Rankin Scale (MRS) score ≤ 4.

    • Ability to be randomized within 3 to 180 days after stroke onset.

    • ESUS, defined as all of the following:

    • Stroke detected by CT or MRI that is not lacunar. Lacunar is defined as a subcortical (this includes pons and midbrain) infarct in the distribution of the small, penetrating cerebral arteries whose largest dimension is ≤1.5 cm on CT or ≤2.0 cm on MRI diffusion images/<1.5 cm on T2 weighted MR images. The following are not considered lacunes: multiple simultaneous small deep infarcts, lateral medullary infarcts, and cerebellar infarcts. Patients with a clinical lacunar stroke syndrome and no infarct on imaging are excluded.

    • Absence of extracranial or intracranial atherosclerosis causing ≥50 percent luminal stenosis of the artery supplying the area of ischemia. Patients must undergo vascular imaging of the extracranial and intracranial vessels using either catheter angiography, CT angiogram (CTA), MR angiogram (MRA), or ultrasound, as considered appropriate by the treating physician and local principal investigator.

    • No major-risk cardioembolic source of embolism, including intracardiac thrombus, mechanical prosthetic cardiac valve, atrial myxoma or other cardiac tumors, moderate or severe mitral stenosis, myocardial infarction within the last 4 weeks, left ventricular ejection fraction <30 percent, valvular vegetations, or infective endocarditis). Patent foramen ovale is not an exclusion. All patients must undergo electrocardiogram, transthoracic or transesophageal echocardiography (TTE or TEE) and at least 24 hours of cardiac rhythm monitoring (Holter monitor or telemetry or equivalent). Additional cardiac imaging, such as cardiac MRI, or cardiac CT will be performed at the discretion of the local treating physician and principal investigator. Additional cardiac rhythm monitoring, such as monitored cardiac outpatient telemetry (MCOT) or an implanted cardiac monitor, will be at the discretion of the treating physician and local principal investigator.

    • No other specific cause of stroke identified, such as arteritis, dissection, migraine, vasospasm, drug abuse, or hypercoagulability. Special testing, such as toxicological screens, serological testing for syphilis, and tests for hypercoagulability, will be performed at the discretion of the treating physician and local principal investigator.

    Exclusion Criteria:
    • History of atrial fibrillation (AF), AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization.

    • Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.

    • Need for antiplatelet agent, such as aspirin or clopidogrel

    • History of spontaneous intracranial hemorrhage.

    • Chronic kidney disease with serum creatinine ≥2.5 mg/dL.For Canadian sites only, estimated creatinine clearance (eCrCl) <15 mL/min is also an exclusion criterion.

    • Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.

    • Clinically significant bleeding diathesis.

    • Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).

    • Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).

    • At risk for pregnancy: premenopausal or postmenopausal woman within 12 months of last menses without a negative pregnancy test or not committing to adequate birth control, which includes an oral contraceptive, two methods of barrier birth control such as condom with or without spermicidal lubricant + diaphragm, or abstinence.

    • Known allergy or intolerance to aspirin or apixaban.

    • Concomitant participation in another clinical trial involving a drug or acute stroke intervention.

    • Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.

    • Inability of either participant or surrogate to provide written, informed consent for trial participation.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Birmingham Alabama United States 35233
    2 University of South Alabama University Hospital Mobile Alabama United States 36604
    3 Chandler Regional Medical Center Chandler, AZ Chandler Arizona United States 85224
    4 St. Joseph's Hospital and Medical Center Phoenix Arizona United States 85013
    5 Banner University Medical Center - Tucson Tucson Arizona United States 85724
    6 UAMS Medical Center Little Rock Arkansas United States 72205
    7 Mercy San Juan Medical Center (Dignity Health) Carmichael California United States 95608
    8 Eden Medical Center Castro Valley California United States 94546
    9 Rancho Los Amigos National Rehabilitation Center Downey California United States 90242
    10 Community Regional Medical Center Fresno California United States 93721
    11 UCSD Health La Jolla La Jolla California United States 92037
    12 Sharp Grossmont Hospital La Mesa California United States 92123
    13 Long Beach Memorial Medical Center Long Beach California United States 90806
    14 Los Alamitos Medical Center Los Alamitos California United States 90720
    15 Kaiser Permanente Los Angeles California United States 90027
    16 Keck Hospital Of USC Los Angeles California United States 90033
    17 Los Angeles County- USC Medical Center Los Angeles California United States 90033
    18 VA Greater Los Angeles - West LA VA Medical Center Los Angeles California United States 90073
    19 Ronald Reagan UCLA Medical Center Los Angeles California United States 90095
    20 UC Irvine Medical Center Orange California United States 92868
    21 Desert Regional Medical Center Palm Springs California United States 92262
    22 Sutter Medical Center Sacramento California United States 95816
    23 Salinas Valley Memorial Hospital Salinas California United States 93901
    24 Scripps Mercy San Diego California United States 91910
    25 UCSD Medical Center - Hillcrest Hospital San Diego California United States 92103
    26 Kaiser Permanent San Diego Medical Center San Diego California United States 92123
    27 Sharp Memorial Hospital San Diego California United States 92123
    28 San Francisco General San Francisco California United States 94110
    29 UCSF Medical Center San Francisco California United States 94143
    30 Regional Medical Center San Jose California United States 95116
    31 Good Samaritan San Jose California United States 95124
    32 Stanford University Medical Center Stanford California United States 94305
    33 Los Robles Hospital Thousand Oaks California United States 91360
    34 Swedish Medical Center Englewood Colorado United States 80113
    35 St. Mary's Medical Center Grand Junction Colorado United States 81501
    36 Hartford Hospital Hartford Connecticut United States 06102-5037
    37 Yale New Haven Hospital New Haven Connecticut United States 06520
    38 Christiana Hospital Newark Delaware United States 19718
    39 Med-star Georgetown Univ. Washington District of Columbia United States 20007
    40 Medstar Washington Washington District of Columbia United States 20010
    41 Boca Raton Regional Hospital Boca Raton Florida United States 33486
    42 UF Health Shands Gainesville Florida United States 32610
    43 Baptist Medical Center Jacksonville Jacksonville Florida United States 32207
    44 Mayo Clinic Jacksonville Florida United States 32224
    45 Jackson Memorial Miami Florida United States 33136
    46 Univ. Miami Hospital Miami Florida United States 33136
    47 Baptist Hospital of Miami Miami Florida United States 33176
    48 Bruce W. Carter VA Miami Florida United States 33176
    49 Intercoastal Medical Group - Hyde Park Sarasota Florida United States 34239
    50 Tampa General Tampa Florida United States 33606
    51 Emory University Atlanta Georgia United States 30303
    52 Grady Memorial Atlanta Georgia United States 30303
    53 The Queen's Medical Center Honolulu Hawaii United States 96813
    54 Northwestern Memorial Hospital Chicago Illinois United States 60611
    55 Rush University Chicago Illinois United States 60612
    56 University of Illinois Chicago Illinois United States 60612
    57 University of Chicago Medical Center Chicago Illinois United States 60637
    58 OSF St. Francis Medical Center Peoria Illinois United States 61637
    59 Southern Illinois University Memorial Medical Center Springfield Illinois United States 62702
    60 St. John's Hospital (Prairie Research) Springfield Illinois United States 62769
    61 Central DuPage Hospital Winfield Illinois United States 60190
    62 Mercy Medical Center Cedar Rapids Iowa United States 52403
    63 Genesis Medical Center West Davenport Iowa United States 52803
    64 Genesis Medical Center Davenport Iowa United States 52804
    65 University of Iowa Iowa City Iowa United States 52242
    66 University of Kansas Kansas City Kansas United States 66160
    67 University of Kentucky Lexington Kentucky United States 40536
    68 University of Louisville Hospital Louisville Kentucky United States 40202
    69 Ochsner Medical Center New Orleans Louisiana United States 70121
    70 Eastern Maine Medical Center Bangor Maine United States 04401
    71 University of Maryland Medical Center Baltimore Maryland United States 21201
    72 Tufts Medical Center Boston Massachusetts United States 02111
    73 Massachusetts General Hospital Boston Massachusetts United States 02114
    74 Boston Medical Center Boston Massachusetts United States 02118
    75 Beth Israel Deaconess Medical Boston Massachusetts United States 02215
    76 Brigham & Womens Hospital Boston Massachusetts United States 20115
    77 Lahey Hospital & Medical Center Burlington Massachusetts United States 01805
    78 U Mass Memorial Medical Center Worcester Massachusetts United States 01655
    79 University of Michigan University Hospital Ann Arbor Michigan United States 48109
    80 VA Ann Arbor Healthcare System Ann Arbor Michigan United States 48109
    81 Detroit Receiving Hospital Detroit Michigan United States 48201
    82 Henry Ford Hospital Detroit Michigan United States 48202
    83 McLaren Flint Flint Michigan United States 48532
    84 Mercy Health St. Mary's Grand Rapids Michigan United States 49503
    85 Spectrum Health Grand Rapids Michigan United States 49503
    86 McLaren Macomb, Mount Clemens, MI Mount Clemens Michigan United States 48043
    87 Abbott Northwestern Hospital Minneapolis Minnesota United States 55407
    88 Hennepin County Minneapolis Minnesota United States 55415
    89 Univ. of Minnesota Minneapolis Minnesota United States 55455
    90 Mayo Clinic Rochester Minnesota United States 55905
    91 Regions Hospital, St. Paul Saint Paul Minnesota United States 55101
    92 United Hospital Saint Paul Minnesota United States 55102
    93 University of Mississippi Medical Center Jackson Mississippi United States 39216
    94 Saint Luke's Hospital of Kansas City Kansas City Missouri United States 64111
    95 St. Louis University Hospital Saint Louis Missouri United States 63104
    96 Barnes Jewish Hospital Saint Louis Missouri United States 63110
    97 Cox Medical Center South Springfield Missouri United States 65807
    98 University of Nebraska Omaha Nebraska United States 68198
    99 Cooper University Hospital, Camden New Jersey United States 08103
    100 Robert Wood Johnson New Brunswick New Jersey United States 08901
    101 St. Josephs Regional Paterson New Jersey United States 07503-2621
    102 Capital Health Medical Center Hopewell Pennington New Jersey United States 08534
    103 Univ. New Mexico Albuquerque New Mexico United States 87131
    104 Montefiore Medical Center Bronx New York United States 10467
    105 Kings County Hospital Brooklyn New York United States 11203
    106 New York Presbyterian - Brooklyn Methodist Hospital Brooklyn New York United States 11215-3609
    107 Maimonides Medical Center Brooklyn New York United States 11219
    108 NYU Langone Hospital - Brooklyn Brooklyn New York United States 11220
    109 Mount Sinai Beth Israel Brooklyn Brooklyn New York United States 11234
    110 Buffalo General Medical Center Buffalo New York United States 14203
    111 North Shore University Hospital Manhasset New York United States 11042
    112 NYU Langone New York New York United States 10003
    113 Mount Sinai West New York New York United States 10019
    114 Columbia University Medical Center New York New York United States 10032
    115 Weill Cornell Medicine New York New York United States 10065
    116 Lenox Hill Hospital New York New York United States 10075
    117 Strong Memorial Hospital Rochester New York United States 14642
    118 Moses H. Cone Memorial Hospital Greensboro North Carolina United States 27405
    119 Wake Forest Baptist Medical Center Winston-Salem North Carolina United States 27157
    120 Sanford Medical Center Fargo Fargo North Dakota United States 58122
    121 Akron General Medical Center Akron Ohio United States 44307
    122 University of Cincinnati Cincinnati Ohio United States 45219
    123 Louis Stokes VA Medical Center Cleveland Ohio United States 44106
    124 UH Cleveland Medical Center Cleveland Ohio United States 44106
    125 MetroHealth Medical Center Cleveland Ohio United States 44109
    126 Cleveland Clinic Cleveland Ohio United States 44195
    127 OSU Wexner Columbus Ohio United States 43210
    128 Ohio Health Riverside - Riverside Methodist Hospital Columbus Ohio United States 43214
    129 Miami Valley Hospita Dayton Ohio United States 45409
    130 Mercy St Vincent Medical Center Toledo Ohio United States 43608
    131 OU Medical Center Oklahoma Oklahoma City Oklahoma United States 73104
    132 St. John Medical Center Tulsa Oklahoma United States 74104
    133 Legacy Emanuel Portland Oregon United States 97227
    134 Oregon Health and Sciences Portland Oregon United States 97239
    135 Lehigh Valley Hospital Allentown Pennsylvania United States 18103
    136 UPMC Altoona Altoona Pennsylvania United States 16601
    137 Hospital of the University of Pennsylvania Philadelphia Pennsylvania United States 19104
    138 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    139 Temple University Philadelphia Pennsylvania United States 19140
    140 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    141 UPMC Presbyterian Pittsburgh Pennsylvania United States 15213
    142 Rhode Island Hospital Providence Rhode Island United States 02903
    143 Medical University of South Carolina Charleston South Carolina United States 29425
    144 Prisma Health Richland Hospital (formerly Palmetto Health) Columbia South Carolina United States 29203
    145 Prisma Health Greenville Memorial Hospital Greenville South Carolina United States 29605
    146 Fort Sanders Regional Medical Center Knoxville Tennessee United States 37916
    147 Methodist University Hospital Memphis Tennessee United States 38104
    148 Vanderbilt Nashville Tennessee United States 37212
    149 UT Southwestern Medical Center Dallas Texas United States 75390
    150 DHR Health Edinburg Texas United States 78539
    151 Valley Bapist Harlingen Texas United States 78550
    152 Baylor College College of Medicine Houston Texas United States 77030
    153 Houston Methodist Hospital Houston Texas United States 77030
    154 Memorial Hermann Texas Medical Center Houston Texas United States 77030
    155 Univ of Texas Health Science Center San Antonio San Antonio Texas United States 78229
    156 Scott & White Memorial Hospital - Temple Temple Texas United States 76508
    157 Memorial Hermann The Woodlands Hospital The Woodlands Texas United States 77380
    158 Intermountain Medical Center Murray Utah United States 84107
    159 Utah Valley Regional Medical Center Provo Utah United States 84604
    160 Univ of Utah Salt Lake City Utah United States 84132
    161 George E Whalen VA Salt Lake City Utah United States 84148
    162 UVA Medical Center Charlottesville Virginia United States 22908
    163 Bon Secours St. Mary's Hospital Richmond Virginia United States 23226
    164 Providence St. Peter Hospital Olympia Washington United States 98506
    165 Harborview Medical Center Seattle Washington United States 98104
    166 Puget Sound VA Seattle Washington United States 98108
    167 Swedish Medical Center - Cherry Hill Campus Seattle Washington United States 98122
    168 WVU Healthcare Ruby Memorial Morgantown West Virginia United States 26506-9180
    169 University of Wisconsin Madison Wisconsin United States 53792
    170 Aurora St. Luke's Medical Center Milwaukee Wisconsin United States 53215
    171 Froedtert Hospital Milwaukee Wisconsin United States 53226
    172 University of Calgary - Foothills Medical Centre Calgary Alberta Canada T2N2T9
    173 University of Alberta Hospital Edmonton Alberta Canada T6G 2G3
    174 Neurologic Research Center Lethbridge Alberta Canada T1J 0N9
    175 Kelowna General Hospital Kelowna British Columbia Canada V1Y 1T2
    176 Vancouver General Hospital Vancouver British Columbia Canada V5Z 1M9
    177 Brandon Regional Health Center Brandon Manitoba Canada R7A 2B3
    178 Hamilton General Hospital Hamilton Ontario Canada L8L2X2
    179 Kingston General Hospital Kingston Ontario Canada K7L2V7
    180 London Health Sciences Center London Ontario Canada N6A 5A5
    181 Stroke Prevention & Atherosclerosis Research Centre (SPARC) London Ontario Canada N6G 2V4
    182 Sunnybrook Health Sciences Center Toronto Ontario Canada M4N 3M5

    Sponsors and Collaborators

    • Columbia University
    • 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

    Investigators

    • Principal Investigator: Mitchell SV Elkind, MD, Columbia University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Mitchell S Elkind, Professor of Neurology and Epidemiology in the Gertrude H. Serg, Department of Neurology Stroke, Columbia University
    ClinicalTrials.gov Identifier:
    NCT03192215
    Other Study ID Numbers:
    • AAAR4607
    • 1U01NS095869-01A1
    First Posted:
    Jun 20, 2017
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Mitchell S Elkind, Professor of Neurology and Epidemiology in the Gertrude H. Serg, Department of Neurology Stroke, Columbia University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Apr 6, 2022