Clinical trial NCT05974033: IntraCranial Angiography-derived Fraction Flow-guided Percutaneous Transluminal Angioplasty and Stenting Versus Medical Therapy (ICAS-MT)
Official title: IntraCranial Angiography-derived Fraction Flow-guided Percutaneous Transluminal Angioplasty and Stenting Versus Medical Therapy (ICAS-MT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: ICAS - Intracranial Atherosclerosis
Keywords: ICAS
Cerebral Arteriosclerosis
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2023-08-03
Enrollment: 536
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Stroke or death
timeFrame: 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 outcomes:
measure: Ischemic stroke in the target vessel territory
timeFrame: Within 1-3 years after enrollment
measure: Ischemic stroke in non-target vessel territory
timeFrame: Within 30 days to 1 year, and within 1-3 years after enrollment
measure: Any occurrence of cerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage
timeFrame: Within 30 days to 3 years after enrollment
measure: Any cause of death
timeFrame: Within 30 days to 3 years after enrollment
measure: mRS score
timeFrame: At 1 year, 2 years, and 3 years after enrollment
measure: National Institutes of Health Stroke Scale (NIHSS) score
timeFrame: At 1 year, 2 years, and 3 years after enrollment
measure: Barthel Index
timeFrame: At 1 year, 2 years, and 3 years after enrollment
Other outcomes:
Locations:
Study officials:
affiliation: Changhai Hospital
name: Jianimin Liu, M.D.
role: PRINCIPAL_INVESTIGATOR
References: