Drug Eluting Stenting and Aggressive Medical Treatment for Preventing Recurrent Stroke in Intracranial Atherosclerotic Disease Trial

Study Overview
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Brief Summary
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The aim of DREAM-PRIDE is to evaluate whether implantation of drug-eluting stent (DES) combined with aggressive medical treatment is more efficacious in prevention of 1-year stroke recurrence than standard medical treatment alone for symptomatic intracranial atherosclerotic disease.

Detailed Description
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This trial is a prospective, multi-center, 1:1 randomized using drug-eluting (Sirolimus) stent combined with aggressive medical treatment versus standard medical treatment to treat symptomatic intracranial atherosclerotic disease. Primary efficacy endpoints (any of the following): 1) any stroke or death within 30 days after enrollment, 2) any stroke or death within 30 days after a revascularization procedure of the qualifying lesion during follow-up, 3) ischemic stroke in the territory of the qualifying artery beyond 30 days to 1 year.

Official Title
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Drug Eluting Stenting and Aggressive Medical Treatment for Preventing Recurrent Stroke in Intracranial Atherosclerotic Disease Trial: a Prospective, Randomized, Open-labelled, Blinded End-point Trial (DREAM-PRIDE)

Conditions
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Intracranial Atherosclerotic Disease, Stroke

Intervention / Treatment
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* Device: Drug Eluting Stent implantation
* Drug: Aggressive medical treatment
* Behavioral: Risk factor management
* Drug: Standard medical treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age from 18 to 85 years Patients with ischemic stroke within 30 days of enrolment attributed to 70% to 99% stenosis of a major intracranial artery (internal carotid artery [C4-C7], middle cerebral artery [M1], vertebral artery [V4], or basilar artery) on CTA (According to WASID method) The diameter of the target vessel between 2.0mm - 4.5mm The stenosis lesion length ≤ 14 mm Baseline modified Rankin Scale (mRS) score ≤ 3 Patient understands the purpose and requirements of the study, and has provided informed consent Exclusion Criteria: Ischemic stroke occurred within 7 days before enrolment Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion (NOTE: an exception is allowed if stenosis or occlusion involves a single vertebral artery proximal to a symptomatic basilar artery stenosis and the contralateral vertebral artery is supplying the basilar artery) Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which artery is symptomatic (NOTE: an exception is that if bilateral vertebral arteries with 70%-99% stenosis but unequal in size, the dominant side is considered as symptomatic) Unilateral vertebral artery stenosis of 70%-99% with normal contralateral vertebral artery Stroke caused by perforating artery occlusion CT angiographic evidence of severe calcification at target lesion Any history of brain parenchymal or subarachnoid, subdural or extradural haemorrhage in the past 6 weeks Intracranial artery stenosis caused by non-atherosclerotic lesions, including: arterial dissection, Moyamoya disease, vasculitis disease, herpes zoster, varicella-zoster or other viral vascular diseases, neurosyphilis, any other intracranial infections, any intracranial stenosis related to cerebrospinal fluid cells, radiation-induced vascular disease, fibromuscular dysplasia, sickle cell disease, neurofibromatosis, central nervous system benign vascular disease, postpartum vascular disease, suspected vasospasm, suspicious embolism recanalization, etc History of stenting of an intracranial artery Presence of any unequivocal cardiac source of embolism Combined with intracranial tumor, aneurysm or intracranial arteriovenous malformation Cannot tolerate dual antiplatelet therapy Contraindications to heparin, rapamycin, contrast and local or general anesthesia Hemoglobin<100g/L, platelet count <100×109/L Severe hepatic and renal dysfunction INR>1.5 or there are uncorrectable factors leading to bleeding Major surgery within the past 30 days or planned within 90 days Renal artery, iliac artery, and coronary artery requiring simultaneous intervention Life expectancy <1 year Pregnant or lactating women Cannot complete the follow-up due to cognitive, emotional or mental illness Other situations that are not suitable for enrolment according to the judgement of the investigator Enrolment in another study that would conflict with the current study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug-eluting stent implantation with aggressive medical treatment group<br>DES implantation (The Maurora ® Sirolimus Eluting Stent System) combined with aggressive medical treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 mg per day, or ticagrelor 90 mg twice per day for 6 months); management of risk factors (hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise) | Device: Drug Eluting Stent implantation<br>* The Maurora ® Sirolimus Eluting Stent System for intracranial PTA treatment comprises of a balloon expandable sirolimus eluting stent and a delivery catheter that features a rapid exchange catheter design with a semi-compliant balloon located at its distal end.<br>* Other names: Maurora ® Sirolimus Eluting Stent implantation;Drug: Aggressive medical treatment<br>* Aggressive medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 6 months after enrollment).<br>* Other names: Dual antiplatelet therapy for 6 months;Behavioral: Risk factor management<br>* Management of risk factors (hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise)<br>* Other names: Risk factor and life style management;|
| Active Comparator: Standard medical treatment group<br>Standard medical treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 mg per day, or ticagrelor 90 mg twice per day for 3 months after enrolment), management of risk factors (hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise) | Behavioral: Risk factor management<br>* Management of risk factors (hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise)<br>* Other names: Risk factor and life style management;Drug: Standard medical treatment<br>* Standard medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 3 months after enrollment).<br>* Other names: Dual antiplatelet therapy for 3 months;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Any stroke or death within 30 days of enrollment or any revascularization procedure OR an ischemic stroke in the territory of the symptomatic intracranial artery between 31 day to 1 year. | Primary endpoints are composite event of (1) any stroke or death within 30 days after enrollment, (2) any stroke or death within 30 days after revascularization procedure of the qualifying lesion during follow-up, and (3) ischemic stroke in the territory of the qualifying artery from 31 days to 1 year. Ischemic stroke is defined as a new focal neurological deficit of sudden onset, that is associated with infarction lesion on CT or MRI. Ischemic strokes are classified as in or out of the territory of the symptomatic intracranial artery. Symptomatic brain hemorrhage is defined as parenchymal, subarachnoid, or intraventricular hemorrhage detected by CT or MRI that isassociated with new neurological signs or symptoms (headache, change in level of consciousness, focal neurological symptoms) lasting ≥ 24 hours or a seizure. | 12 months after enrollment | 
| Severe or moderate bleeding (GUSTO score) | Bleeding events were defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification for severe or life-threatening, moderate, or mild bleeding: Severe or life-threatening- Either intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention Moderate- Bleeding that requires blood transfusion but does not result in hemodynamic compromise Mild- Bleeding that does not meet criteria for either severe/life-threatening or moderate bleeding | 12 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Residual stenosis after the procedure in DES group | Degree of residual stenosis was measured and caculated according to the methods of the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial. | At the end of the procedure | 
| In-stent restenosis (ISR) rate in DES group within 12 months | The ISR is defined as >50% stenosis within or immediately adjacent (within 5 mm) of the implanted stent and >20% absolute luminal loss. | 12 months after enrollment | 
| Disabling stroke within 1 year | defined as modified Rankin Scale > 3 at 1 year visit | 12 months after enrollment | 
| Any stroke, death or myocardial infarction within 1 year | Any stroke included ischemic stroke and symptomatic brain hemorrhage. Symptomatic brain hemorrhage refers to parenchymal, subarachnoid, or intraventricular hemorrhage that was associated with a seizure or with symptoms or signs lasting 24 hours or longer. | 12 months after enrollment | 
| Major non-stroke hemorrhage within 1 year | A major non-stroke-related hemorrhage was defined as any subdural or epidural hemorrhage or a systemic hemorrhage requiring hospitalization, blood transfusion, or surgery. | 12 months after enrollment | 
| Modified Rankin Scale score at 1 year | The range of modified Rankin Scale was from 0 to 6. 0-No symptoms;1-No significant disability;2-Slight disability;3-Moderate disability;4-Moderately severe disability;5-Severe disability;6 -Dead.A higher score indicates worse a outcome. | 12 months after enrollment | 
| Death within 1 year | Death within 1 year | 12 months after enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracranial Atherosclerotic disease, Stroke, Drug-eluting stent, Medical treatment