Extended CTA for Ischemic Stroke Detection

(DAYLIGHT Trial)

Overseen By Diana Ayan, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Disqualifiers: Allergy to contrast, Pregnancy, Renal disease, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 1 year

830 Participants Needed

Trial Summary

What is the purpose of this trial?

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 left atrial appendage (LAA), left atrium (LA), left ventricle (LV), valves, or aortic arch. The most frequently used diagnostic method in clinical practice to detect cardioaortic thrombi 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, LV, or cardiac valves. 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 6 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 or selection bias. 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment extended CTA for ischemic stroke detection?

Research suggests that using advanced CT techniques like CTA can help identify areas of the brain that might still be saved after a stroke, which can lead to better treatment decisions and outcomes compared to using standard CT scans alone. ^{1 2 3 4 5}

Is extended CTA generally safe for humans?

Research indicates that using contrast-enhanced CT for evaluating acute ischemic stroke does not increase the risk of kidney problems from the contrast dye. However, there are known risks like radiation exposure and potential adverse effects from the contrast dye used in CTA. ^{6 7 8 9 10}

How does the extended CTA treatment differ from other treatments for ischemic stroke?

Extended CTA (computed tomography angiography) is unique because it provides a detailed view of blood vessels in the brain, helping to assess the extent of collateral circulation, which is crucial for determining the best treatment approach for acute ischemic stroke. This method is non-invasive and can improve patient management by identifying those who may benefit from reperfusion therapies, potentially leading to better outcomes. ^{3 11 12 13 14}

Research Team

Rodrigo Bagur, MD

Principal Investigator

London Health Sciences Center, Western University

Luciano Sposato, MD

Principal Investigator

London Health Sciences Center, Western University

Eligibility Criteria

The DAYLIGHT trial is for adults who come to the emergency department or stroke clinic with a suspected stroke or mini-stroke. They don't need a confirmed diagnosis to join. However, pregnant individuals, those with severe kidney disease, past or active cancers of the head, neck, or chest; allergies to iodine-based contrast agents; or without vein access for IV contrast are excluded.

Inclusion Criteria

I may not have had a stroke or TIA to join, but need one confirmed for certain study parts.

I am an adult being checked for a stroke at University Hospital in London, Ontario.

Exclusion Criteria

I don't have conditions that prevent me from having a CTA scan for stroke.

Allergy to iodinated contrast agents

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either standard CTA or extended CTA as part of the stroke workup

1 year

Regular visits as per standard of care

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Optional extended monitoring for participants with detected cardioaortic thrombi

Long-term

Treatment Details

Interventions

• extended CTA

Trial Overview This study tests if an extended CT angiography (eCTA) can better detect blood clots in the heart's left atrial appendage compared to standard CT angiography (sCTA). Both groups will receive usual care for stroke evaluation but one group will have additional imaging extending below the carina.

Participant Groups

Group I: extended CTA Experimental Treatment 1 Intervention

The standard CTA will be extended 6 cm below the carina

Group II: standard CTA Active Control 1 Intervention

Standard CTA performed as standard of care for Stroke Workup

Who Is Running the Clinical Trial?

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

In a study of 50 patients treated with thrombolytic therapy for hyperacute stroke, advanced imaging techniques like CT, CTA, and perfusion CT were found to be more effective in identifying ischemic areas and salvageable brain tissue compared to routine non-contrast CT.

The use of advanced CT imaging allowed for better patient triage for thrombolysis, leading to clinical improvement in 58% of patients, with a low complication rate of only 4% experiencing subsequent bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging impact of CTA/perfusion CT on acute stroke thrombolysis in a community hospital. Brant-Zawadzki, MN., Brown, DM., Whitaker, LA., et al.[2019]

In a study of 54 patients with acute neurological deficits, combining CT angiography (CTA) results with the NIH Stroke Scale improved the specificity for predicting clinical outcomes, especially in cases with no arterial occlusion.

Knowledge of CTA results sometimes led to more conservative treatment decisions for thrombolysis, indicating that while CTA can enhance decision-making, it may also result in less aggressive interventions in certain cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of CT angiography in acute ischemic stroke. Verro, P., Tanenbaum, LN., Borden, N., et al.[2016]

Cardiac and large artery sources are major contributors to acute ischemic stroke, highlighting the need for effective evaluation methods.

Using advanced CT angiography (CTA) for early assessment of these patients can enhance management and outcomes while potentially reducing healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of cardiac and extracranial vascular CT in the evaluation/management of cerebral ischemia and stroke. Kamalian, S., Kamalian, S., Pomerantz, SR., et al.[2021]

In a study of 85 stroke patients, performing CT angiography (CTA) before perfusion CT (PCT) did not significantly affect the quantitative perfusion parameters, indicating that the order of these tests may not impact the diagnostic quality.

However, conducting CTA before PCT resulted in significantly shorter examination times, which is crucial for timely treatment in stroke patients, while also avoiding issues with venous contrast enhancement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal sequence timing of CT angiography and perfusion CT in patients with stroke. Morhard, D., Wirth, CD., Reiser, MF., et al.[2019]

A systematic review of 12 studies involving 17,481 patients found that computed tomography angiography (CTA) did not significantly improve outcomes such as recurrent stroke, mortality, or disability compared to other imaging methods in ischemic stroke and transient ischemic attacks (TIAs).

The quality of evidence regarding the effectiveness of CTA was rated as low to very low, indicating a need for more high-quality research to determine its true impact on patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient Outcomes With Use of Computed Tomography Angiography in Acute Ischemic Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis. Li, SS., Trajkovski, A., Siarkowski, M., et al.[2020]

In a study of 56 patients with primary intracerebral hemorrhage (ICH), active contrast extravasation observed on CT scans was found to independently predict both increased mortality and hematoma growth.

The presence of contrast extravasation was significant in multivariate analyses, indicating that it is a reliable predictor of poor outcomes in ICH patients, alongside factors like initial hematoma size and clinical scores.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast extravasation on CT predicts mortality in primary intracerebral hemorrhage. Kim, J., Smith, A., Hemphill, JC., et al.[2022]

In a study of 918 patients with acute ischemic stroke, those who received iodinated contrast agents during CT imaging had a lower incidence of acute nephropathy (AN) at 5% compared to 10% in those who did not receive contrast, suggesting that contrast use may not be as risky as previously thought.

Patients who underwent conventional angiography after contrast-enhanced CT did not show a higher risk of acute nephropathy compared to those who only had the CT imaging, indicating that the use of contrast in these procedures is safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy. Lima, FO., Lev, MH., Levy, RA., et al.[2021]

In a study of 120 patients with CT-confirmed or suspected intracranial hemorrhage, cerebral computed tomography angiography (CTA) revealed abnormalities in 42% of cases, including aneurysms in 27% and arteriovenous malformations (AVM) in 8%.

Despite its diagnostic value, over half (58%) of the patients had normal CTA results or findings unrelated to the hemorrhage, highlighting the need for careful clinical judgment to weigh the risks of radiation exposure and intravenous contrast against the potential benefits of the CTA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of computed tomography angiogram in intracranial hemorrhage. Do the benefits justify the known risks in everyday practice? Alshumrani, G., Al Abo Nasser, B., Alzawani, A., et al.[2021]

In a study of 1097 patients undergoing non-coronary cardiac CT angiography (CTA), the most common reason for the procedure was to evaluate pulmonary vein anatomy, highlighting its importance in cardiac assessments.

The procedure demonstrated a very low complication rate of 1.5% and provided new clinical diagnostic information in 3.2% of cases, indicating its safety and potential to uncover important health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic report on non-coronary cardiac CTA in 1097 patients from the German cardiac CT registry. Gitsioudis, G., Marwan, M., Schneider, S., et al.[2021]

A systematic review and meta-analysis of 4 studies indicated that contrast extravasation on CT angiography is strongly associated with a higher risk of hematoma expansion in traumatic brain injury, with a relative risk of 5.75.

Contrast extravasation was also linked to worse neurological outcomes and increased mortality, with relative risks of 3.25 and 2.77, respectively, highlighting its importance as a predictive imaging sign in TBI cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The extravasation of contrast as a predictor of cerebral hemorrhagic contusion expansion, poor neurological outcome and mortality after traumatic brain injury: A systematic review and meta-analysis. Baldon, IV., Amorim, AC., Santana, LM., et al.[2020]

Modern multi-slice computed tomography (MSCT) is now the preferred method for quickly evaluating neurological emergencies due to its rapid examination times and broad availability.

MSCT angiography is increasingly replacing traditional diagnostic digital subtraction angiography (DSA) for assessing conditions like intracranial aneurysms and acute strokes, enhancing detection rates and potentially improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Neurologic emergencies and multislice computed tomography]. Eftimov, L., Morhard, D., Reiser, M., et al.[2021]

The cerebral collateral circulation is crucial for preserving brain tissue at risk during an ischemic stroke, and its assessment through computed tomography angiography (CTA) can guide treatment decisions.

Multi-phase CTA (mCTA) is found to be superior to single-phase CTA (sCTA) in evaluating collateral circulation, making it a promising tool for identifying patients with acute ischemic stroke who may benefit from reperfusion therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pivotal role of multiphase computed tomography angiography for collateral assessment in patients with acute ischemic stroke. Busto, G., Morotti, A., Carlesi, E., et al.[2023]

In a study of 27 patients with acute subarachnoid hemorrhage, combining perfusion CT (PCT) with CT angiography (CTA) proved to be a highly accurate method for diagnosing vasospasm, achieving an accuracy of 93% when using mean transit time (MTT) thresholds.

PCT demonstrated a higher positive predictive value (89.9%) for identifying vasospasm compared to transcranial Doppler (TCD) ultrasonography (62.9%), suggesting that PCT may be a more reliable tool for guiding treatment decisions in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vasospasm after subarachnoid hemorrhage: utility of perfusion CT and CT angiography on diagnosis and management. Wintermark, M., Ko, NU., Smith, WS., et al.[2022]

In a study of 266 patients with embolic stroke of undetermined source (ESUS), cardiac computed tomography angiography (CCTA) detected intra-cardiac thrombi in 17% of those who underwent the procedure, which could significantly influence treatment decisions.

CCTA identified 22 patients (8.2% of the entire ESUS cohort) with thrombi that were otherwise missed by standard echocardiography, suggesting that incorporating CCTA into routine ESUS workup can enhance secondary prevention strategies for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac CT for intra-cardiac thrombus detection in embolic stroke of undetermined source (ESUS). Barnea, R., Agmon, IN., Shafir, G., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Emerging impact of CTA/perfusion CT on acute stroke thrombolysis in a community hospital. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical application of CT angiography in acute ischemic stroke. [2016]

3. United States pubmed.ncbi.nlm.nih.gov

Role of cardiac and extracranial vascular CT in the evaluation/management of cerebral ischemia and stroke. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Optimal sequence timing of CT angiography and perfusion CT in patients with stroke. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Patient Outcomes With Use of Computed Tomography Angiography in Acute Ischemic Stroke and Transient Ischemic Attack: A Systematic Review and Meta-Analysis. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Contrast extravasation on CT predicts mortality in primary intracerebral hemorrhage. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The role of computed tomography angiogram in intracranial hemorrhage. Do the benefits justify the known risks in everyday practice? [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

A systematic report on non-coronary cardiac CTA in 1097 patients from the German cardiac CT registry. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

The extravasation of contrast as a predictor of cerebral hemorrhagic contusion expansion, poor neurological outcome and mortality after traumatic brain injury: A systematic review and meta-analysis. [2020]

11. Germany pubmed.ncbi.nlm.nih.gov

[Neurologic emergencies and multislice computed tomography]. [2021]

12. Italy pubmed.ncbi.nlm.nih.gov

Pivotal role of multiphase computed tomography angiography for collateral assessment in patients with acute ischemic stroke. [2023]

13. United States pubmed.ncbi.nlm.nih.gov

Vasospasm after subarachnoid hemorrhage: utility of perfusion CT and CT angiography on diagnosis and management. [2022]

14. England pubmed.ncbi.nlm.nih.gov

Cardiac CT for intra-cardiac thrombus detection in embolic stroke of undetermined source (ESUS). [2022]