Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence

Cryptogenic Stroke Clinical Trial

— CASPR  

Official title:

Cardiac Abnormalities in Stroke Prevention and Risk of Recurrence (CASPR): A Multi-center Observational Cohort Study

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06398366
• Other study ID #: 22-165
• Status: Enrolling by invitation
• Start date: September 14, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: The Cooper Health System
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2000
• Est. completion date: December 31, 2026
• Est. primary completion date: May 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 90 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

Related Conditions & MeSH terms

• Cryptogenic Stroke
• Ischemic Stroke
• Recurrence
• Stroke

Locations

Country	Name	City	State
United States	Cooper Health System	Camden	New Jersey

Sponsors (26)

Lead Sponsor

Collaborator

The Cooper Health System

Allina Health System, Beth Israel Lahey Health, Boston Medical Center, Christiana Care Health Services, Covenant Health, Dartmouth-Hitchcock Medical Center, Duke University, Emory University, Henry Ford Health System, Mayo Clinic, Medical University of South Carolina, Ohio State University, Rhode Island Hospital, The University of Texas Health Science Center, Houston, Thomas Jefferson University, University of California, Los Angeles, University of Chicago, University of Colorado, Denver, University of Iowa, University of Maryland, Baltimore, University of Pennsylvania, University of Tennessee, Virginia Commonwealth University, West Virginia University, Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of potential embolic sources	Epidemiological estimates of prevalence of various potential embolic sources in the cryptogenic stroke population will be calculated across the cohort	through study completion, an average of 2 years
Primary	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	. This outcome will be evaluated across each subgroup of potential embolic source (e.g., valvular lesions present vs. absent, nonstenotic carotid plaque present or absent). Adjusted estimates of event probability will be calculated between patients treated with various antithrombotic types (or class, e.g. anticoagulant vs. antiplatelet) using propensity score matching according to propensity of antithrombotic use	At any point during follow-up over a minimum of 90 days after stroke (average of 2 years)
Primary	Number of patients treated with antiplatelet, anticoagulant, or combination antithrombotic therapy	Following the index cryptogenic stroke, the outcome of specific antithrombotic treatment will be compared between patient groups (antiplatelet, anticoagulant, combination antithrombotic)	through study completion, an average of 2 years