Digital Angiography-Derived Fractional Flow Assessment for Intracranial Stenosis

NCT ID: NCT07309705

Last Updated: 2025-12-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 400 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-12-01
• Study Completion Date: 2028-01-01

Brief Summary

The goal of this observational study is to learn whether a digital angiography derived fractional flow reserve (DPR) measurement can improve the prediction of stroke risk in adults with symptomatic intracranial atherosclerotic stenosis, defined as 50 to 99 percent narrowing.

The main questions it aims to answer are:

Does DPR identify patients who are at higher risk of recurrent stroke despite receiving standard medical treatment? Is DPR more accurate than traditional angiographic stenosis measurements for assessing the functional severity of intracranial arterial disease?

Participants will undergo routine digital subtraction angiography as part of their clinical evaluation. Their angiographic images will be analyzed using a computational method to estimate blood flow impairment, and they will be followed for up to 12 months to monitor stroke related outcomes.

Detailed Description

Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, representing ~15% of cases in Western populations and up to 46.6% in Asia. Even with intensive medical therapy, annual stroke recurrence remains high (7.2-20%), prompting exploration of additional treatment strategies. Early trials such as SAMMPRIS and VISSIT suggested worse outcomes with stenting compared with aggressive medical therapy, largely due to concerns over operator experience, patient selection, and timing. Subsequent analyses showed that patients with hemodynamic compromise-such as watershed infarction and poor collaterals-have recurrence rates up to 37%, underscoring the central role of impaired cerebral perfusion.

Although more recent studies (CASSISS, BASIS) demonstrated that endovascular therapy may be safe and effective in carefully selected patients, current ICAS assessment relies primarily on stenosis severity, which correlates only weakly with true hemodynamic impairment and is insufficient for accurate risk stratification. Because symptoms arise principally from reduced perfusion, physiologic evaluation is essential.

Fractional flow reserve (FFR) is the gold standard for assessing coronary lesion significance and guiding intervention through translesional pressure gradients. Attempts to translate this approach to ICAS using invasive pressure wires have shown feasibility but remain limited by anatomical differences, lack of dedicated devices, procedural risks, and unclear outcome thresholds.

Our prior work demonstrated that intracranial translesional pressure gradients correlate strongly with cerebral blood flow in both animal models and clinical settings, validating hemodynamic relevance. To overcome the limitations of invasive measurements, the present study seeks to develop and evaluate a noninvasive, angiography-derived pressure ratio (DPR) using routine digital subtraction angiography. This method allows physiologic assessment without pressure wires and may reduce procedural risk.

The objectives of this project are to establish a computational DPR technique, determine its association with clinical outcomes, identify a hemodynamic threshold for stroke-risk stratification, and validate its performance in a prospective multicenter cohort. By enabling early identification of high-risk ICAS patients who may respond poorly to medical therapy, DPR has the potential to improve treatment selection and outcomes, ultimately advancing strategies for stroke prevention.

Conditions

Intracranial Atherosclerosis ICAS; Hemodynamic; Stroke

Keywords

Intracranial Atherosclerotic Stenosis; Recurrent Stroke Risk; Hemodynamic Impairment; Fractional Flow Reserve; Precision Risk Stratification

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

CASSISS-DPR

Standardized medical therapy targeting vascular risk factors and stroke prevention

Intervention Type: DRUG

Dual antiplatelet treatment and management of vascular risk factors, in accordance with AHA/ASA guidelines

Interventions

Standardized medical therapy targeting vascular risk factors and stroke prevention

Dual antiplatelet treatment and management of vascular risk factors, in accordance with AHA/ASA guidelines

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with intracranial atherosclerotic stenosis (ICAS) of the anterior circulation.

2. History of an ischemic cerebrovascular event related to the target artery within the past 12 months, including ischemic stroke involving less than one-half of the middle cerebral artery territory or transient ischemic attack.

3. Age between 18 and 80 years.

4. Stenosis severity of 50% to 99% identified by transcranial Doppler ultrasound, CT angiography, or MR angiography, and confirmed as 50% to 99% stenosis on digital subtraction angiography.

5. Good compliance, willingness to sign written informed consent, and ability to complete follow-up.

Exclusion Criteria

1. Non-atherosclerotic intracranial stenosis such as moyamoya disease, vasculitis, or arterial dissection.

2. Coexisting ipsilateral arterial stenosis greater than 50% other than the target lesion.

3. Large territorial infarction on MRI DWI involving at least one-half of the MCA territory with a modified Rankin Scale score greater than 3.

4. Contraindications to the use of antiplatelet agents or statins.

5. Inability to undergo DSA because of severe iodinated contrast allergy, severe hyperthyroidism, severe coagulation abnormalities with high bleeding risk, or severe cardiac, hepatic, or renal insufficiency.

6. Pregnant or breastfeeding women.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Suining Hospital of Traditional Chinese Medicine

UNKNOWN

Sponsor Role: collaborator

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital of Zhengzhou University

OTHER

Sponsor Role: collaborator

Xuanwu Jinan Hospital

UNKNOWN

Sponsor Role: collaborator

The First Affiliated Hospital of University of Science and Technology of China

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

Jiangmen Central Hospital

OTHER

Sponsor Role: collaborator

Hebi People's Hospital

UNKNOWN

Sponsor Role: collaborator

Shanghai Sixth People's Hospital Anhui Branch

UNKNOWN

Sponsor Role: collaborator

Xuanwu Hospital, Beijing

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Neurosurgery, Xuanwu hospital

Beijing, Xicheng District, China

Countries

China

Other Identifiers

WKZX2025CZ0401

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CASSISS-DPR

Identifier Type: -

Identifier Source: org_study_id