Comparison of Perioperative Conscious Sedation During Endovascular Thrombectomy in Acute Ischemic Stroke

Study Overview
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Brief Summary
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This study aims to conduct a multicenter, prospective, randomized clinical trial to scientifically evaluate the safety and efficacy of different perioperative sedation methods during endovascular thrombectomy in acute ischemic stroke patients with large vessel occlusion in the anterior circulation.

Detailed Description
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In the perioperative period of endovascular thrombectomy, the main sedation options are midazolam (MDZ) and dexmedetomidine (DEX). Research has shown that both sedation methods have their advantages and disadvantages, and there is no consensus on how to choose between them. Therefore, this study aims to conduct a multicenter, prospective, randomized clinical trial to scientifically evaluate the safety and efficacy of different perioperative sedation methods during endovascular thrombectomy (EVT) in AIS patients with large vessel occlusion in the anterior circulation and hopes to contribute to the advancement of EVT in clinical practice. In this trial, acute ischemic stroke patients with large vessel occlusion in the anterior circulation within 24 hours of symptom onset or last known well will be included. In the screening stage, participants who meet the inclusion criteria of the trial, upon completion of screening/baseline assessment and after signing the informed consent, will be randomly assigned in a 1:1 ratio to one of the following two treatment groups: the dexmedetomidine and midazolam conscious sedation groups. The primary end point is the proportion of modified Ranking score of 0-2 at 90 days.

Official Title
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Comparison of Perioperative Conscious Sedation During Endovascular Thrombectomy in Acute Ischemic Stroke (PEACE) A Randomised Multicentre Trial

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Presenting with symptoms of acute ischemic stroke CTA or MRA confirmed occlusion of the anterior circulation (intracranial carotid artery or M1, M2 segment of the middle cerebral artery) Randomization finished within 24 hours of symptom onset or time last know well Pre-stroke mRS score ≤2 NIHSS score ≥6 at the time of randomization ASPECTS value ≥3 Informed consent signed Exclusion Criteria: General exclusion criteria Pregnant or lactating women Known allergy to contrast agents or nitinol devices Known allergy to midazolam or other benzodiazepines Known allergy to dexmedetomidine or its components Planned to receive general anesthesia for EVT Uncontrolled hypertension or hypotension (defined as systolic blood pressure >185 mmHg or < 90 mmHg, diastolic blood pressure >110 mmHg or < 60 mmHg) Second-degree or third-degree heart blockage or bradyarrhythmia with a baseline heart rate lower than 50 beats/min Any major surgery or serious trauma within 14 days Known genetic or acquired bleeding diathesis (platelet count < 100\*109 /L, activated partial thromboplastin time > 50 s or international normalized ratio > 1.7) Blood glucose <2.8 or > 22.2 mmol/L Severe renal insufficiency (defined as glomerular filtration rate <30 ml/min or serum creatinine >220 mmol/L (2.5mg/dl)) Receiving hemodialysis or peritoneal dialysis Life expectancy less than 1 year Severe agitation or seizures Clinical manifestations of central nervous system vasculitis Premorbid neurological disease or mental disorders confounding evaluation Unwilling to be followed up within 90 days Participation in other interventional randomized clinical trials Imaging exclusion criteria 1. Evidence of intracranial hemorrhage on CT or MRI 2. Cerebellar infarction with obvious space-occupying effects and fourth ventricle compression on CT or MRI 3. Any untreated or incompletely treated intracranial aneurysm or any intracranial vascular malformation 4. Bilateral occlusion or multiple intracranial vessels occlusions 5. Intracranial tumors (with mass effect)

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the dexmedetomidine group<br>In the experimental group, dexmedetomidine is used for intraoperative sedation. Dexmedetomidine is prepared as an 8μg/ml intravenous infusion. It begins with an initial loading dose of 1μg/kg, administered over a period exceeding 10 minutes. | Drug: Dexmedetomidine<br>* Patients receive perioperative sedation with dexmedetomidine<br>|
| Active Comparator: the midazolam group<br>In the control group, midazolam is used for intraoperative sedation. Midazolam is prepared as a 1mg/ml intravenous infusion. It starts with an initial intravenous push of 0.05mg/kg, followed by a maintenance dose of 0.04-0.2mg/kg administered intravenously via an infusion pump. | Drug: Midazolam<br>* Patients receive perioperative sedation with midazolam<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of mRS score 0-2 at 90 days | mRS is short for modified Ranking score (ranging from 0 to 6, with higher values indicating a worse functional outcome). | 90 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Shift in the distribution of mRS scores at 90 days | mRS is short for modified Ranking score (ranging from 0 to 6, with higher values indicating a worse functional outcome). | 90 days after randomization | 
| The proportion of mRS score 0-1 at 90 days | mRS is short for modified Ranking score (ranging from 0 to 6, with higher values indicating a worse functional outcome). | 90 days after randomization | 
| The proportion of mRS score 0-3 at 90 days | mRS is short for modified Ranking score (ranging from 0 to 6, with higher values indicating a worse functional outcome). | 90 days after randomization | 
| Rates of successful recanalization | Successful recanalization is defined as mTICI≥2b. mTICI is short for modified Thrombolysis in cerebral Infarction (ranging from 0 to 3, with higher values indicating a better reperfusion state). | Immediately after the thrombectomy procedure is completed | 
| Changes of ASPECTS score at 24-72 hours | ASPECTS is short for Alberta Stroke Program Early CT Score (ranging from 0 to 10, with a higher score indicating a better perfusion state). | 24-72 hours after randomization | 
| Recanalization rate on CTA/MRA at 24-72 hours | Recanalization is defined as mTICI≥2b assessed with CTA/MRA. mTICI is short for modified Thrombolysis in cerebral Infarction (ranging from 0 to 3, with higher values indicating a better reperfusion state). | 24-72 hours after randomization | 
| The infarct volume on 24-72 hours follow-up imaging | Infarct volume is evaluated by brain CT/MRI | 24-72 hours after randomization | 
| RASS score between -3 and -1 during procedure | RASS is short for Richmond Agitation and Sedation Scale. RASS is a score of the degree of sedation (range from -5 to +4, higher values indicate a worse sedation state). | During operation | 
| Changes of the GCS score at 24 hours | GCS is short for Glasgow Coma Scale. GCS is a score of the degree of comma (range from 3 to 15, higher values indicate more severe comma). | 24 hours after randomization | 
| Changes of the NIHSS score at 24 hours | NIHSS is short for National Institute of Health stroke scale. NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits). | 24 hours after randomization | 
| Changes of the GCS score at 5-7 days | GCS is short for Glasgow Coma Scale. GCS is a score of the degree of comma (range from 3 to 15, higher values indicate more severe comma). | 5-7 days after randomization | 
| Changes of the NIHSS score at 5-7 days | NIHSS is short for National Institute of Health stroke scale. NIHSS is a stroke severity score composed of 11 items (range from 0 to 42, higher values indicate more severe deficits). | 5-7 days after randomization | 
| EQ-5D at 90 days | EQ-5D is short for EuroQol Five Dimensions Questionnaire. EQ-5D is a five-dimension score (higher values indicate a worse prognosis). | 90 days after randomization | 
| Barthel Index at 90 days | Barthel Index is an ordinal disability score of 10 categories (range from 0 to 100, higher values indicate better prognosis) | 90 days after randomization |