Clevidipine Infusion for Blood Pressure Management After Successful Revascularization in Acute Ischemic Stroke

Study Overview
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Brief Summary
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The CLEVER Study is a prospective, 2-arm, randomized, single-center pilot study to assess the safety and efficacy of intensive blood pressure control using Clevidipine (on-label use) in AIS patients undergoing standard of care mechanical thrombectomy (MT) within 24-hours of symptoms onset.

Detailed Description
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The CLEVER Study is a prospective, 2-arm, randomized, single-center pilot study to assess the safety and efficacy of intensive blood pressure control using Clevidipine (on-label use) in AIS patients undergoing standard of care mechanical thrombectomy (MT) within 24-hours of symptoms onset. Eligible patients will be randomized 1:1 to a systolic blood pressure goal after successful MT (mTICI 2c or greater) of either: 90-120mmHg (Intensive BP management group) or 90-160mmHg (Standard BP management group). Patients enrolled into the study will be followed and assessed for up to 3 months.

Official Title
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Clevidipine Infusion for Blood Pressure Management After Successful Revascularization in Acute Ischemic Stroke (CLEVER)

Conditions
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Stroke, Acute, Blood Pressure, Mechanical Thrombectomy

Intervention / Treatment
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* Drug: Clevidipine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age 18 or older 2. Acute hypertension (systolic blood pressure of greater than 140 mmHg) at recanalization 3. Anterior circulation ischemic stroke symptoms and confirmed occlusion (ICA, M1, or M2) on angiogram with mechanical thrombectomy initiated within 24 hours since last known well 4. Success revascularization score of mTICI 2c or higher after mechanical thrombectomy 5. ASPECTS score of greater than 6 6. Premorbid mRS 0-4 7. Signed informed consent within 30 minutes from end of MT procedure. Exclusion Criteria: 1. Presence of any hemorrhage and/or ASPECT score ≤6 on baseline head CT scan 2. Pregnant or lactating 3. Acute traumatic brain injury 4. Patient on active dialysis 5. Intracranial neoplasm 6. Acute or recent STEMI in the last 30 days 7. Severe arrhythmias, unstable cardiac function 8. Any terminal medical condition with life expectancy less than 6 months 9. Concurrent enrollment in another trial that could confound the results of this study

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
Interventional Model Description: Eligible patients will be randomized 1:1 to a systolic blood pressure goal after successful MT (mTICI 2c or greater) of either: 90-120 or 90-160mmHg.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intensive blood pressure management group<br>Target blood pressure of 90-120mmHg (Intensive BP management group) | Drug: Clevidipine<br>* Blood pressure management with Clevidipine<br>|
| Active Comparator: Standard blood pressure management group<br>Target blood pressure of 90-160mmHg (Standard BP management group) | Drug: Clevidipine<br>* Blood pressure management with Clevidipine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint (Drug-related) | Time to target blood pressure | Time from drug initiation to target blood pressure, up to 24 hours after study drug adminstration | 
| Primary Safety Endpoint (Disease-related) | Incidence of any hemorrhagic conversion at 24 hours | 24 hours from the time of treatment with Clevidipine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Drug-related | The efficacy of Clevidipine in maintaining BP within range using area under the curve (AUC) analysis of BP excursions beyond predetermined upper and lower limits using statistical models from the ECLIPSE Trials. | Up to 24 hours after study drug adminstration | 
| Drug-related, Rate of hypotension requiring intervention | Rate of hypotension requiring intervention | Up to 24 hours after study drug adminstration | 
| Drug-related, Rate of hypotension and severe hypertension | Rate of hypotension and severe hypertension | Up to 24 hours after study drug adminstration | 
| Disease-related, Incidence of symptomatic intracerebral hemorrhage | Incidence of symptomatic intracerebral hemorrhage (sICH), defined as any intracranial hemorrhage and neurologic worsening of at least 4 points on the National Institute of Health Stroke Scale (NIHSS), according to the 2nd European-Australasian Acute Stroke Study (ECASS II) criteria within 24 hours of randomization | Within 24 hours of randomization | 
| Disease-related, Delayed ICH after 24 hours | Delayed ICH after 24 hours | Within 24 hours of randomization | 
| Disease-related, Incidence of acute kidney injury | Incidence of acute kidney injury | From drug adminstration to 90 days post-randomization | 
| Disease-related, | Mortality rate at 90 days | 90 days after randomization | 
| Disease-related, Length of hospital stay | Length of hospital stay | Day 6 (+/- 1 day) post-randomization or discharge (whichever sooner) | 
| Disease-related, Use of additional hypertensive agents | Use of additional hypertensive agents | Up to 24 hours after study drug adminstration | 
| Disease-related, Onset of atrial fibrillation or cardiovascular events | Onset of atrial fibrillation or cardiovascular events | Up to 24 hours after study drug adminstration | 
| Disease-related, mRS 0-2 or return to baseline at 90 days | mRS 0-2 or return to baseline at 90 days | 90 days post-randomization |