IntraCranial Angiography-derived Fraction Flow-guided Percutaneous Transluminal Angioplasty and Stenting Versus Medical Therapy (ICAS-MT)

A multicenter, open-label, blinded-endpoint, prospective, randomized controlled clinical trial with an "all comers" design.

Study Overview

• Status: Not yet recruiting
• Conditions: ICAS - Intracranial Atherosclerosis
• Intervention / Treatment: Combination product: Stenting plus medical therapy; Drug: Medical therapy alone

Detailed Description

The main objective of this study is to investigate the impact of angiography-derived fractional flow (Angio-FF) on diagnostic and therapeutic decision-making in patients with symptomatic intracranial atherosclerotic stenosis (sICAS). The study aims to evaluate whether stenting plus medical therapy, compared to medical therapy alone, can benefit patients selected through Angio-FF screening.

For Group A, patients with significant stenosis and hemodynamic impairment identified through Angio-FF (≤0.7) screening are expected to have a higher risk. The patients will be enrolled in RCT trial, with a planned enrollment of 336 subjects.

For Group B, patients with significant stenosis but without hemodynamic impairment identified through Angio-FF (>0.7) screening will be included in the registry cohort, with a planned enrollment of 200 subjects.

• Study Type: Interventional
• Enrollment (Estimated): 536
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pengfei Yang, M.D.; Phone Number: 86-21-31161784; Email: 15921196312@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥30 and ≤80 years old.
2. Symptomatic intracranial atherosclerotic stenosis: Transient ischemic attack (TIA) or stroke related to 70%-99% stenosis in the major intracranial arteries (intracranial segment of the internal carotid artery, M1 segment of the middle cerebral artery, V4 segment of the vertebral artery, and basilar artery) within the past 3 months.
3. Only one target vessel with 70-99% stenosis confirmed by angiography for enrollment in the trial (WASID criteria).
4. Patients with ischemic stroke should be performed with stenting beyond a duration of 2 weeks from the latest ischemic symptom onset, patients with TIA have no time restriction.
5. Pre-enrollment modified Rankin Scale (mRS) score ≤2.
6. Target vessel reference diameter must be measured to be 2 mm to 4.5 mm, target area of stenosis is less than or equal to 14mm in length.
7. Patients required to meet at least with one atherosclerotic risk factors, including hypertension, diabetes, hyperlipidemia, hyperhomocysteinemia, coronary heart disease, obesity, smoking history, and atherosclerosis in other arterial vessels.
8. Negative pregnancy test in a female who has had any menses in the last 18 months.
9. Patient is willing and able to return for all follow-up visits required by the protocol.
10. Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.

Exclusion Criteria:

1. Intracranial arterial stenosis not caused by atherosclerotic lesions, such as arterial dissection, moya-moya disease, vasculitic disease, viral vascular lesions (e.g., herpes zoster, varicella), neurosyphilis, other intracranial infections, radiation-induced vasculopathy, fibromuscular dysplasia, sickle cell disease, neurofibromatosis, benign central nervous system vascular diseases, postpartum angiopathy, suspected vasospastic process, suspected recanalized embolus, etc.
2. Any conditions that precludes proper angiographic assessment.
3. Preoperative MRI indicating only lacunar infarction in the target lesion territory.
4. History of subarachnoid hemorrhage, subdural or epidural hematoma within 30 days prior to enrollment, or untreated chronic subdural hematoma thickness≥5mm, or history of primary intracerebral hemorrhage.
5. At risk of hemorrhagic transformation during the procedure (CT or MRI showing infarct area diameter >5 cm); hemorrhagic transformation of an ischemic stroke within the past 15 days (detected by CT).
6. Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion
7. Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which lesion is symptomatic (for example, if patient has pon, midbrain, temporal and occipital symptoms).
8. Stenting, angioplasty, or endarterectomy of an extracranial (carotid or vertebral artery) or intracranial artery within 30 days prior to expected enrollment date.
9. Previous treatment of target lesion with a stent, angioplasty, or other mechanical device, or plan to perform staged angioplasty followed by stenting of target lesion
10. Severe vascular tortuosity, severe calcification, or other factors that would preclude the safe introduction of a guiding catheter, guiding sheath or stent placement.
11. Presence of intraluminal thrombus proximal to or at the target lesion.
12. Any aneurysm proximal to or distal to intracranial stenotic artery.
13. Intracranial tumors or any intracranial vascular malformations.
14. Potential cardiac sources of emboli such as atrial fibrillation, left ventricular thrombus, heart valve replacement, atrial septal defect, ventricular septal defect, atrial myxoma, etc.
15. Myocardial infarction within previous 30 days.
16. Suspected severe allergy or contraindication to vascular interventional-related drugs or devices, such as aspirin, clopidogrel, general anesthesia agents, heparin, contrast agents, nitinol alloy, etc.
17. Active bleeding diathesis or coagulopathy, active gastrointestinal ulcer, major systemic hemorrhage within 30 days, active bleeding diathesis, platelets count <100,000, hematocrit <30, INR >1.5, dysfunctions of the blood coagulation system.
18. uncontrolled severe hypertension (systolic BP>180mm Hg or diastolic BP>110mm Hg)
19. Severe comorbidities or unstable conditions, such as severe heart failure, respiratory failure, or renal failure (serum creatinine>264μmol/L, unless on dialysis), severe liver dysfunction (ALT or ALT >3 times normal), malignant tumors.
20. Major surgery performed within 30 days prior to enrollment or planned inpatient surgery within 90 days after enrollment.
21. Pregnancy or intent to become pregnant during the trial period.
22. Currently participating in another clinical trial.
23. Life expectancy less than 3 years
24. Patients unable to complete follow-up due to cognitive impairment, emotional disorders, or mental illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; Stenting plus medical therapy	Combination product: Stenting plus medical therapy; Patients randomized to intervention group received the percutaneous transluminal balloon angioplasty with stenting within 5 days after randomization, and loading dose of aspirin and clopidogrel was allowed. Received aspirin, 100mg, plus clopidogrel, 75 mg, daily for 90 days after procedure.
Active Comparator: Control group; Medical therapy alone	Drug: Medical therapy alone; Medical therapy alone: received aspirin, 100mg, plus clopidogrel, 75 mg, daily for 90 days after randomisation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke or death	Stroke or death within 30 days after enrollment; Or stroke in the territory of the symptomatic intracranial artery (SIT) between 30 days and 1 year.	Stroke or death within 30 days after enrollment; Or stroke in the territory of the symptomatic intracranial artery (SIT) between 30 days and 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic stroke in the target vessel territory	Ischemic stroke in the target vessel territory	Within 1-3 years after enrollment
Ischemic stroke in non-target vessel territory	Ischemic stroke in non-target vessel territory	Within 30 days to 1 year, and within 1-3 years after enrollment
Any occurrence of cerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage	Any occurrence of cerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage	Within 30 days to 3 years after enrollment
Any cause of death	Any cause of death	Within 30 days to 3 years after enrollment
mRS score	Modified Rankin scale (mRS) score. The value range 0-6: higher scores mean a worse outcome.	At 1 year, 2 years, and 3 years after enrollment
National Institutes of Health Stroke Scale (NIHSS) score	Stroke severity (NIHSS score). The value range 0-42: higher scores mean a worse outcome.	At 1 year, 2 years, and 3 years after enrollment
Barthel Index	An ordinal scale which measures a person's ability to complete activities of daily living. The value range 0-100: higher scores mean a better outcome.	At 1 year, 2 years, and 3 years after enrollment

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Investigators: Principal Investigator: Jianimin Liu, M.D., Changhai Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: July 25, 2023
• First Submitted That Met QC Criteria: August 1, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: ICAS; Cerebral Arteriosclerosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intracranial Arterial Diseases; Atherosclerosis; Intracranial Arteriosclerosis
• Other Study ID Numbers: ICAS-MT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data can be shared with bona fide researchers after the publication of the main results, based on a submitted protocol to Oriental Collaboration group on Emerging Advanced therapy for Neurovascular diseases Consortium.
• IPD Sharing Time Frame: Data sharing will be available from 12 months after the publication of the main results.
• IPD Sharing Access Criteria: The data sharing will be only for the purposes of health and medical research and within the constraints of the consent under which the data were originally gathered.; The Custodian of the Collection will not consider any Proposals for data sharing that unblind, or potentially unblind, randomised comparisons in active / ongoing trials.; Requesters should be employees of a recognised academic institution, health service organisation, commercial research organisation or from the pharmaceutical industry. Requesters must have experience in medical research.; Requesters must be able to demonstrate through their peer review publications in the area of interest their ability to carry out the proposed use of the requested dataset from a Collection.; The Requesters must not have a conflict of interest that may potentially influence their interpretation of any analyses
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No