In one-third of ischemic strokes, a specific cause cannot be identified. Many of these cryptogenic strokes appear to arise from a distant embolic source. Recent evidence suggests that some cryptogenic strokes arise from left atrial thromboembolism that goes unrecognized because it is not associated with atrial fibrillation/flutter (AF). Under the prevailing clinical paradigm, it is thought that AF is required for blood clots to form in the left atrium. Therefore, unless AF is apparent, patients do not receive anticoagulant therapy to prevent atrial thromboembolism. However, recent research indicates that embolization from the left atrium can occur when there are abnormal changes to atrial tissue and function even before there is AF. Such an “atrial cardiopathy” may explain many of the strokes that are currently of unknown cause. Since anticoagulant drugs such as apixaban have already proven more effective than standard aspirin therapy for preventing stroke from AF, the parallels between AF and atrial cardiopathy suggest that apixaban may also be more effective than aspirin for stroke prevention in patients with atrial cardiopathy and no AF.
ARCADIA is a randomized trial of apixaban versus aspirin specifically in patients with cryptogenic stroke who have evidence of atrial cardiopathy. This trial will address several important knowledge gaps. First, it will advance our understanding of stroke pathophysiology by assessing whether atrial cardiopathy is a valid therapeutic target, which may set the stage for a primary prevention trial. Second, this trial will advance our understanding of optimal secondary stroke prevention therapy.
Trial Design Summary:
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. Atrial cardiopathy will be defined as one or more of the following biomarkers: P-wave terminal force in electrocardiogram lead V1 >5,000 mV*ms, left atrial size index ≥3.0 cm/m2 on echocardiogram, and serum NT-proBNP >250 pg/mL. The primary aim is to test the hypothesis that apixaban is superior to aspirin for the prevention of recurrent stroke in subjects with cryptogenic ischemic stroke and atrial cardiopathy.
ARCADIA will recruit 1,100 subjects over 2.5 years at 120 sites in the NINDS StrokeNet consortium. Subjects will be followed for a minimum of 1.5 years and a maximum of 4 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.
ARCADIA Payment Schedule
ARCADIA trial methods paper Int J Stroke 2018
Sponsors and Collaborators:
Sponsor: Columbia University/Mitchell S.V. Elkind, MD, MS for the ARCADIA PIs
National Institute of Neurological Disorders and Stroke (NINDS)
Also supported by: BMS-Pfizer Partnership and Roche Diagnostics
Investigator Meetings: Principal Investigators:
ARCADIA Investigator Meeting November 17, 2017
Mitchell S.V. Elkind, MD, MS, Columbia University
Hooman Kamel, MD, Cornell University
W.T. Longstreth Jr, MD, MPH, University of Washington
David L. Tirschwell, MD, MSC, University of Washington
FDA, CDRH: IDE: # G130221
- ARCADIA Website: Pending
- ClinicalTrials.gov Identifier: NCT03192215
- Trial WebSite Link: Pending