drugset / Trial / NCT03192215
AtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke
Phase 3
Terminated
1015 enrolled
Columbia University
Bristol-Myers Squibb · collabMedical University of South Carolina · collabNational Institute of Neurological Disorders and Stroke (NINDS) · collabPfizer · collabRoche Pharma AG · collabUniversity of Cincinnati · collabUniversity of Washington · collabWeill Medical College of Cornell University · collab
RandomizedParallel-groupQuadruple-blindPrevention
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.
Timeline
- Start
- 2018-01-19
- Primary completion
- 2023-03-31
- Completion
- 2023-04-17
Outcome
Missed primary endpoint
Stopped: “The DSMB halted the trial prematurely due to futility without any safety concerns.”
registry p = 0.99; Hazard Ratio (HR) 1.0 (95% CI 0.64 to 1.55) NCT03192215 ↗
paper In patients with cryptogenic stroke and evidence of atrial cardiopathy without atrial fibrillation, apixaban did not significantly reduce recurrent stroke risk compared with aspirin. PMID 38324415 ↗
Publications
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Background 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.
- Ridha 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.
- Boursiquot BC, Elias A, Kamel H, Kronmal R, Marcus GM, Di Tullio MR, Tirschwell D, Elkind MSV, Longstreth WT, Soliman EZ; ARCADIA Trial Investigators. Prolonged QT interval and risk of recurrent stroke in the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial. Heart. 2026 Feb 20:heartjnl-2025-327253. doi: 10.1136/heartjnl-2025-327253. Online ahead of print.
- Lazar 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.
- Elias 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.
- Navi 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.
- Lansberg 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.
- Navi 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.
- Navi 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.
- Kamel 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Apixaban | Small molecule | 2.5 mg | Oral |
| Subject | Apixaban | Small molecule | 5 mg | Oral |
| Comparator | Aspirin | Small molecule | 81 mg | Oral |