ComputeD tomogrAphy angiographY for Left atrIal appendaGe tHrombus Detection in Acute Ischemic sTroke (DAYLIGHT) Trial

Study Overview
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Brief Summary
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Embolic strokes of undetermined source (ESUS) represent a subset of cryptogenic strokes that are suspected to have an occult embolic source. The risk of stroke recurrence in patients with ESUS varies between 1.9%/year and 19.0%/year depending on the prevalence of vascular risk factors. Part of the elevated recurrence rate is due to the inability to identify high-risk treatable causes such as cardiac thrombi as those found in the LAA.The most frequently used diagnostic method in clinical practice to detect an LAA thrombus is transesophageal echocardiography (TEE). However, the relatively low availability, higher cost, and invasive nature of TEE limit its large-scale usability. In most stroke centers, patients presenting with an acute ischemic stroke or TIA undergo a tomography (CT) angiography (CTA) of the neck and intracranial vessels. This standard of care CTA (sCTA) classically includes the aortic arch, the higher portion of the ascending/descending aorta, and the rostral portion of the cardiac chambers, but does not involve the LAA. A recent study performed among 300 patients with an acute ischemic stroke showed an overall LAA thrombus detection of 6.6% and 15% in patients with AF by extending the CTA 3 cm below the carina.This is an extraordinarily high prevalence of LAA compared to 0.5% to 4.8% of intracardiac thrombi identified on TEE in most previous studies. The major limitation of previous CTA and TEE studies is their observational design, so the differing prevalence of LAA thrombi could be explained by dissimilar population characteristics. Based on the methodological limitation of prior studies and the promising role of extended CTAs (eCTA), a randomized controlled trial comparing eCTA + standard of care stroke workup vs. sCTA + standard of care stroke workup is needed.

Detailed Description
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Between 16% and 25% of patients with ischemic strokes do not have an identifiable cause after a full stroke workup, and their strokes are classified as cryptogenic. Embolic strokes of undetermined source (ESUS) represent a subset of cryptogenic strokes that are suspected to have an occult embolic source. The risk of stroke recurrence in patients with ESUS varies between 1.9%/year and 19.0%/year depending on the prevalence of vascular risk factors. Part of the elevated recurrence rate is due to the inability to identify high-risk treatable causes such as cardiac thrombi as those found in the LAA.The most frequently used diagnostic method in clinical practice to detect an LAA thrombus is transesophageal echocardiography (TEE). However, the relatively low availability, higher cost, and invasive nature of TEE limit its large-scale usability. In most stroke centers, patients presenting with an acute ischemic stroke or TIA undergo a tomography (CT) angiography (CTA) of the neck and intracranial vessels. This standard of care CTA (sCTA) classically includes the aortic arch, the higher portion of the ascending/descending aorta, and the rostral portion of the cardiac chambers, but does not involve the LAA. A recent study performed among 300 patients with an acute ischemic stroke showed an overall LAA thrombus detection of 6.6% and 15% in patients with AF by extending the CTA 3 cm below the carina.This is an extraordinarily high prevalence of LAA compared to 0.5% to 4.8% of intracardiac thrombi identified on TEE in most previous studies. The major limitation of previous CTA and TEE studies is their observational design, so the differing prevalence of LAA thrombi could be explained by dissimilar population characteristics. Based on the methodological limitation of prior studies and the promising role of extended CTAs (eCTA), a randomized controlled trial comparing eCTA + standard of care stroke workup vs. sCTA + standard of care stroke workup is needed. Demonstrating that performing an eCTA can significantly increase the detection of LAA thrombi compared to sCTA has three important implications with the potential to improve clinical practice, patients' outcomes, and clinical guidelines. First, proving that eCTA increases de detection of LAA thrombi in stroke patients in a randomized controlled trial (highest level of evidence) may result in guidelines recommending this novel approach and stroke sites adopting this technique globally. Second, the higher detection of LAA thrombi may increase the use of oral anticoagulants, which have proven efficacy for the prevention of recurrent strokes in patients with cardiac thrombi, ultimately resulting in fewer stroke recurrences. However, proving the latter concept would require a larger randomized clinical trial with stroke recurrence as the primary efficacy endpoint. Third, the LAA is the most frequent source of thromboembolism in patients with AF and LAA thrombi are associated with increased detection of AF on cardiac rhythm monitoring, implying that finding an LAA thrombus may help improve the selection of patients who could benefit from prolonged cardiac monitoring after stroke.

Official Title
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ComputeD tomogrAphy angiographY for Left atrIal appendaGe tHrombus Detection in Acute Ischemic sTroke (DAYLIGHT) Trial

Conditions
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Acute Ischemic Stroke, Transient Ischemic Attack, Left Atrial Appendage Thrombosis

Intervention / Treatment
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* Diagnostic Test: extended CTA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients with a suspected cerebrovascular event who are evaluated in the Emergency Department or the Urgent Stroke Prevention Clinic at University Hospital, London Health Sciences Centre, London, Ontario, Canada. A confirmed diagnosis of stroke or TIA is not mandatory. Exclusion Criteria: Allergy to iodinated contrast agents Pregnancy Lack of a peripheral vein access for intravenous contrast administration Any contraindication for the clinical use of a CTA for hyperacute stroke care (e.g., end-stage renal disease that contraindicates a CTA), and active or past cancer of the head, neck, or chest)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: standard CTA<br>Standard CTA performed as standard of care for Stroke Workup | |
| Experimental: extended CTA<br>The standard CTA will be extended 3 cm below the carina with the aim of increase the LAA thrombus detection | Diagnostic Test: extended CTA<br>* Extending the standard CTA 3 cm below the carina.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome: newly diagnosed LAA thrombus | The proportion of participants with newly diagnosed LAA thrombus at 120 post-stroke and no history of atrial fibrillation. The reason for choosing 120 days of follow-up is that most follow-up visits after the stroke workup is completed are done at 90 days but there may be some delays in some cases. We aim to ensure the largest proportion possible of patients with a complete workup at the time of the study follow-up visit. | 120 days after the qualifying stroke or TIA. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Efficacy Outcome: patients anticoagulated after the CVA event | The proportion of patients receiving oral anticoagulation at 120 days after the qualifying stroke or TIA. | 120 days after the qualifying stroke or TIA. |