Clinical trial NCT06398366: Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence
Official title: Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence (CASPR): a Multi-center Observational Cohort Study
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Cryptogenic Stroke
Keywords: carotid atherosclerosis
heart failure
cardiomyopathy
embolic stroke
Lead sponsor: The Cooper Health System
Sponsor class: OTHER
Collaborators: name: Duke University
name: Covenant Health, Canada
name: University of Colorado, Denver
name: Medical University of South Carolina
name: University of Maryland, Baltimore
name: University of Pennsylvania
name: Emory University
name: University of Chicago
name: University of Tennessee
name: Ohio State University
name: West Virginia University
name: Mayo Clinic
name: Boston Medical Center
name: Rhode Island Hospital
name: Beth Israel Lahey Health
name: Christiana Care Health Services
name: Henry Ford Health System
name: Thomas Jefferson University
name: University of Iowa
name: University of California, Los Angeles
name: Allina Health System
name: Yale University
name: The University of Texas Health Science Center, Houston
name: Dartmouth-Hitchcock Medical Center
name: Virginia Commonwealth University
First posted: 2024-05-03
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Consecutive adult patients (18 yrs of age or older) diagnosed with cryptogenic stroke despite complete neurodiagnostic workup. Patients admitted between 1/1/2016 and 6/30/2022 with acute ischemic stroke will be screened for inclusion.

Brief summary: This is a multi-center retrospective analysis of consecutive adult patients with cryptogenic stroke patients following a comprehensive workup for the underlying stroke etiology. Patients will be eligible for inclusion if the index stroke event occurred between 1/1/2016 and 06/30/2022.

Detailed description: This is an exploratory observational cohort study of existing registry-based clinical, laboratory, and radiographic data. There are multiple pre-specified hypotheses that will be tested using this data set, which include the entire cohort as well as planned subgroup analyses. The analyses center around patients with cryptogenic stroke (no clear stroke mechanism) but who are characterized by "potential embolic sources". These include but are not limited to: left atrial enlargement or dysfunction, left ventricular dysfunction /heart failure with reduced ejection fraction (HFrEF), patent foramen ovale (PFO), paroxysmal atrial fibrillation (pAF), lambl's excrescence, valvular lesions, carotid web, and nonstenotic cervical arterial plaque. A brief summary of several planned hypothesis is itemized below:

1. To evaluate treatment practices in patients with potential embolic sources.
2. To estimate the risk of recurrent stroke, major bleeding, and/or death following an incident stroke event across various potential embolic sources.
3. To compare rates of recurrent stroke, major bleeding, and/or death across various potential embolic sources, when stratified by antithrombotic treatment type.
4. To evaluate type, frequency, and findings of long-term outpatient cardiac event monitoring (for paroxysmal atrial fibrillation). And furthermore, to determine antithrombotic treatment changes following abnormalities detected with such monitoring.
5. To develop and validate a risk prediction model for later atrial fibrillation in cryptogenic stroke by integrating a machine-learning algorithm or convolutional neural network analysis of 12-lead electrocardiographic data with clinical, laboratory, and radiographic parameters.
6. To develop and validate a risk prediction model for later atrial fibrillation, atrial fibrillation burden, and recurrent stroke and/or death using a machine-learning and/or convolutional neural network and/or validated electrophysiologic biomarkers (e.g., p-wave morphology) abstracted from outpatient telemetry, when added to clinical and radiological patient profiles.
7. To compare the sensitivity of various outpatient cardiac telemetry devices for identifying atrial fibrillation.
8. To evaluate real-world treatment practices of patent foramen ovale closure, antithrombotic therapy in patent foramen ovale, and risk of stroke recurrence.
9. To evaluate real-world secondary stroke prevention strategies in patients with heart failure, with and without left ventricular dysfunction.

Eligibility criteria: Inclusion Criteria:

1. Consecutive adult patients (18 yrs of age or older) diagnosed with cryptogenic stroke despite complete neurodiagnostic workup, including the following:

   A. Transthoracic echocardiogram B. EKG and 24h minimum cardiac telemetry C. Cervical and intracranial vessel imaging D. No known and established source of cerebral embolism after completion of the aforementioned testing E. CT or MRI evidence of acute cerebral infarction F. Onset of stroke or last known well within 2 weeks of hospitalization or study inclusion start date (unless time last known well is unknown)
2. Left ventricular ejection fraction greater than or equal to 20%

Exclusion Criteria:

1. Patients with an established stroke mechanism that is diagnosed prior to or at the time of the index stroke event. Examples include but are not limited to:

   A. New diagnosis of atrial fibrillation during index stroke admission, or history of prior atrial fibrillation B. Cervical or intracranial atherosclerosis in a vessel supplying the infarcted brain region, with 50% luminal stenosis by NASCET criteria C. Cervical or intracranial arterial dissection D. Inflammatory vasculopathy (e.g., giant cell arteritis, primary central nervous system angiitis) E. Acute myocardial infarction or cardiac arrest at the time of stroke F. Intracardiac thrombus (e.g., left ventricular, left atrial, left atrial appendage thrombus), irrespective of cardiac function G. Small vessel disease (defined by the presence of a single, subcortical infarction less than 1.5cm in diameter on computed tomography, less than 2.0cm in diameter on diffusion-weighted imaging, or without radiographic evidence of infarction BUT with symptoms consistent with a subcortical syndrome-e.g., pure motor hemiparesis, pure hemisensory impairment, mixed motor-sensory syndrome, ataxic hemiparesis, or dysarthria-clumsy hand syndrome)
2. Patients without follow-up information at 30 days (although patients who expired within 90 days of stroke are still eligible for inclusion)
3. Patients enrolled in a randomized clinical trial in which antithrombotic group is blinded to the investigator
4. Transient ischemic attack
5. Primary intracerebral hemorrhage

Primary outcomes:
measure: Prevalence of potential embolic sources
timeFrame: through study completion, an average of 2 years
measure: The odds of recurrent stroke, major bleeding (according to the International Society of Thrombosis and Hemostasis), and/or death will be estimated across the cohort, with annualized event rates also calculated
timeFrame: At any point during follow-up over a minimum of 90 days after stroke (average of 2 years)
measure: Number of patients treated with antiplatelet, anticoagulant, or combination antithrombotic therapy
timeFrame: through study completion, an average of 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: Camden
country: United States
facility: Cooper Health System
state: New Jersey
Study officials:
affiliation: Cooper Health System
name: Jesse Thon
role: PRINCIPAL_INVESTIGATOR
References: