ARCADIA: AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
Study Details
Study Description
Brief Summary
Objectives
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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.
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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
Arms and Interventions
Arm | Intervention/Treatment |
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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:
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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:
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Outcome Measures
Primary Outcome Measures
- Incidence of recurrent stroke [7 years]
Recurrent stroke of any type (ischemic, hemorrhagic, or of unclear type)
Secondary Outcome Measures
- Incidence of recurrent ischemic stroke or systemic embolism [Up to 7 years]
Secondary efficacy outcome A
- Incidence of recurrent stroke of any type plus death from any cause [Up to 7 years]
Secondary efficacy outcome B
- Incidence of symptomatic intracranial hemorrhage (including symptomatic hemorrhagic transformation of an ischemic stroke). [Up to 7 years]
Primary safety outcome A
- Incidence of major hemorrhage other than intracranial hemorrhage [Up to 7 years]
Primary safety outcome B
- Incidence of death from any cause [Up to 7 years]
Secondary safety outcome
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age ≥ 45 years.
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Clinical diagnosis of ischemic stroke + brain imaging to rule out hemorrhagic stroke.
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Modified Rankin Scale (MRS) score ≤ 4.
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Ability to be randomized within 3 to 180 days after stroke onset.
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ESUS, defined as all of the following:
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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.
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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.
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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:
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History of atrial fibrillation (AF), AF on 12-lead ECG, or any AF of any duration during heart-rhythm monitoring prior to randomization.
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Clear indication for treatment-dose anticoagulant therapy, such as venous thromboembolism or a mechanical heart valve.
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Need for antiplatelet agent, such as aspirin or clopidogrel
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History of spontaneous intracranial hemorrhage.
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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.
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Active hepatitis or hepatic insufficiency with Child-Pugh score B or C.
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Clinically significant bleeding diathesis.
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Unresolved anemia (hemoglobin <9 g/dL) or thrombocytopenia (<100 x 10E9/L).
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Clinically significant gastrointestinal bleeding within the past year (e.g., not due to external hemorrhoids).
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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.
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Known allergy or intolerance to aspirin or apixaban.
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Concomitant participation in another clinical trial involving a drug or acute stroke intervention.
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Considered by the investigator to have a condition that precludes follow-up or safe participation in the trial.
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Inability of either participant or surrogate to provide written, informed consent for trial participation.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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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
- 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. Review.
- 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. Review.
- 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.
- 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. Review.
- 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.
- AAAR4607
- 1U01NS095869-01A1