Safety and Efficacy of Therapeutic INduced HYPERTENSION in Acute Non-cardioembolic Ischemic Stroke (SETIN-HYPERTENSION)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of the induced hypertension using phenylephrine in patients with noncardioembolic ischemic stroke. The investigators hypothesized that phenylephrine induced-hypertension can result in good clinical response without serious complications in patients with noncardioembolic ischemic stroke.

Detailed Description
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See below

Official Title
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Safety and Efficacy of Therapeutic Induced Hypertension in Patients With Acute Non-cardioembolic Ischemic Stroke: A Multicenter, Randomized, Open Label, Prospective, Phase 3 Study

Conditions
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Stroke, Acute, Progressing Stroke

Intervention / Treatment
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* Drug: Phenylephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) performed within 24 hours of symptom onset or symptom worsening(defined by a 2-point or more increase in NIH stroke scale (NIHSS)score including one or more increase in the motor score of affected upper and lower limbs in NIHSS during hospitalization or clear history of symptom worsening judged by investigator before hospitalization) confirmed by DWI performed within 24 hours of aggravation. Baseline NIHSS score 4-18 points Alert mental status Newly developed paresis, aphasia, or neglect Exclusion Criteria: Patients underwent recanalization therapy Systolic blood pressure >170 mmHg at baseline Patients with history or at risk of hemorrhagic stroke History of significant arrhythmia (e.g. atrial fibrillation) Unable to perform MRI scans or undergo MRI scans > 24 hours of symptom onset or progression Large cortical infarction on DWI (more than 1/2 of middle cerebral artery territory) 3 or more cortical microbleeds on gradient-echo MRI Coronary artery disease, congestive heart failure, or hypertrophic cardiomyopathy Anticoagulation therapy (phenylephrine group only) Patients with high-risk cardioembolic sources Cervical or cerebral artery dissection or unruptured aortic/cerebral arterial aneurysm Decreased consciousness Pregnant or Lactating patient Seizure at stroke onset Life expectancy < 6 months Pre-stroke modified Rankin scale (mRS) >= 2 Patients without informed consent
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: Phenylephrine<br>Phenylephrine induced-hypertension arm | Drug: Phenylephrine<br>* Phenylephrine (0.12mg/mL) Starting dose: 10cc/hr Titration: increase 10cc/hr every 30-60min, maximum 160cc/hr rate: increase systolic blood pressure (SBP) 10-25mmHg /hr Target: initially 20% increase of initial SBP, up to improving NIHSS score or SBP 200mmHg<br>|
| No Intervention: Conventional treatment<br>Control arm | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome | 2 points improvement in NIH stroke scale (NIHSS) between days 0 and 7 | Day 0 and Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary efficacy outcome | modified Rankin scale (mRS)≤ 2 at day 90 modified Bathel index (mBI)≥ 90 at day 90 Infarct growth or new ischemic lesion on follow-up MRI | Day 90 for 1, 2 and Day 7 for 3 | 
| Major safety outcome | Symptom aggravation by intracranial hemorrhage or cerebral edema (Clinical deterioration causing an increase in the NIHSS score of more than or equal to 4 points and if the hemorrhage or edema was liley to be the cause of the clinical deterioration) Myocardial infarction death from any cause | From date of randomization until the date of first documented progression by intracranial hemorrhage or cerebral edema, date of myocardial infarction, or date of death from any cause, whichever came first, assessed up to 3 months | 
| Minor safety outcome | Intracranial hemorrhage on follow-up MRI Side effects including headache, arrhythmia, chest pain, dysuria, or gastrointestinal hemorrhage | From date of randomization until the date of first documented intracranial hemorrhage on follow-up MRI, or date of first documented side effects, whichever came first, assessed up to 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, ischemic, Progression, Induced-hypertension, Phenylephrine