Blood Pressure Management in Stroke Following Endovascular Treatment

Study Overview
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Brief Summary
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The aim of DETECT is to prove the feasibility of a multicenter phase III trial testing the hypothesis that intensive blood pressure control immediately after successful endovascular stroke thrombectomy can improve patient outcomes. Patients with stroke who have ongoing high blood pressure after successful clot retrieval will be included. Participants will be randomly placed (like flipping a coin) in one of two groups. There will be a 50% chance of each patient being placed to either group. The first group will be allowed to have a higher blood pressure range that is consistent with current recommendations. The second group will be given medications to bring their blood pressure down into a normal range. These blood pressure targets will be maintained for 48 hours. We will collect patient brain images and levels of stroke disability up to 90 days after their clot retrieval.

Detailed Description
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Current guidelines from the American Heart Association/ American Stroke Association (AHA/ ASA) propose thresholds of systolic blood pressure (BP) less than 180 mm Hg and diastolic BP less than 105 mm Hg during and for the first 24 hours following endovascular treatment (EVT), which have been arbitrarily inherited from previous intravenous thrombolysis guidelines. Although there is plethora of evidence from observational cohort studies suggesting that increased BP following EVT is associated with higher likelihood of both intracranial hemorrhage and unfavorable clinical outcomes, the potential for residual confounding in these observational datasets limits their interpretation. The blooD prEssure management in sTroke following EndovasCular Treatment (DETECT) trial is a single-center, pragmatic, pilot, prospective open label, blinded end point, randomized controlled trial testing the hypothesis that intensive BP management following successful EVT is feasible. The primary objective of DETECT is to determine the feasibility of a RCT assessing the efficacy and safety of intensive BP lowering compared to standard of care in rates of hemorrhagic transformation and functional outcome following successful EVT in acute ischemic stroke patients with large vessel occlusion. We will include adult patients with acute ischemic stroke achieving successful reperfusion (TICI more or equal to 2b) of a proximal large vessel occlusion in the anterior circulation after EVT. Eligible patients will be randomized 1:1 within 60 minutes from the end of the EVT procedure to either intensive (systolic BP target <140 mmHg) or standard BP management (systolic BP target <180 mmHg) for the first 48 hours after randomization. Patients with presence of concomitant ipsilateral or contralateral extracranial vessel occlusion or remaining stenosis ≥80% after the end of the EVT, and/or patients having any medical condition where randomization to either standard or intensive BP lowering would not be acceptable at the discretion of the treating physician will be excluded from participating. The trial will be embedded within an established national EVT registry that focuses on improving quality of management of patients receiving EVT for ischemic stroke.

Official Title
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Blood Pressure Management in Stroke Following Endovascular Treatment

Conditions
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Stroke, Acute, Vessels; Occlusion, Blood Pressure, Endovascular Thrombectomy, Mechanical Thrombectomy

Intervention / Treatment
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* Drug: Labetalol
* Drug: Hydralazine
* Drug: Enalapril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age equal or more than 18 years. Eligible for endovascular treatment (EVT) within 24 hours from symptom onset according to current clinical practice. Presence of a proximal large vessel occlusion in the anterior circulation, defined as occlusion of the intracranial segment of the internal carotid artery and/or occlusion of the M1 segment or proximal M2 segment of the middle cerebral artery. Successful recanalization after the end of the EVT procedure, defined as modified thrombolysis in cerebral ischemia (mTICI) score equal or more than 2b. Sustained elevated systolic BP level after recanalization, defined as 2 consecutive systolic BP readings ≥ 150 mmHg (or ≥ 140 mmHg if the participant has a known history of hypertension) taken more than 5 minutes apart. Ability of the patient or legal representative to provide informed consent. Randomization within 60 minutes from the end of the EVT procedure. Exclusion Criteria: Presence of concomitant ipsilateral or contralateral extracranial vessel occlusion or remaining stenosis ≥80% after the end of the EVT. Symptomatic intracranial hemorrhage after the end of EVT procedure. Any medical condition where randomization to either standard or intensive BP lowering would not be acceptable at the discretion of the investigators and/or the treating physician. Pregnancy. Enrollment in another acute stroke therapeutic trial.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive Blood Pressure management<br>Participants assigned to the intensive blood pressure management arm will be treated using approved antihypertensive medications to have systolic blood pressure readings under 140 mmHg for the first 48 hours after enrollment into the study. | Drug: Labetalol<br>* 10 - 20 mg IV q15 minutes PRN until systolic BP below target (max 300 mg per 24 hours)<br>Drug: Hydralazine<br>* 10 - 20 mg IV bolus q20 min until systolic BP below target (max 240 mg per 24 hours)<br>Drug: Enalapril<br>* 1.25 - 2.5 mg IV bolus and then q6h PRN.<br>|
| Active Comparator: Standard Blood Pressure management<br>Participants assigned to the standard blood pressure management arm will be treated using approved antihypertensive medications to have systolic blood pressure readings under 180 mmHg for the first 48 hours after enrollment into the study. | Drug: Labetalol<br>* 10 - 20 mg IV q15 minutes PRN until systolic BP below target (max 300 mg per 24 hours)<br>Drug: Hydralazine<br>* 10 - 20 mg IV bolus q20 min until systolic BP below target (max 240 mg per 24 hours)<br>Drug: Enalapril<br>* 1.25 - 2.5 mg IV bolus and then q6h PRN.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean enrollment rate. | The predefined target is to achieve a mean enrollment rate of 2 patients per month. | through study completion, an average of 18 months | 
| Number of participants with treatment allocation change. | The predefined target is that at least 80% of the participants remain within their assigned treatment group, and not changing treatment allocation for any reason. | 48 hours from treatment initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with any intracranial hemorrhage. | As identified in the follow-up computed tomography scan. | 24±12 hours from treatment initiation | 
| Absolute difference in flow velocity measurements in transcranial Doppler. | Assessed with the adjusted mean flow velocities of the recanalized vessel on transcranial Doppler examination. | 0-18 hours from treatment initiation | 
| Absolute difference in the NIH Stroke Scale change at day 1. | NIH Stroke Scale ranges from 0 to 42, with higher scores indicating more severe impairment caused by a stroke. | 24±12 hours from treatment initiation | 
| Absolute difference in the NIH Stroke Scale change at day 2. | NIH Stroke Scale ranges from 0 to 42, with higher scores indicating more severe impairment caused by a stroke. | 48±12 hours from treatment initiation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endovascular stroke treatment, successful recanalization, transcranial Doppler Ultrasound, intracranial hemorrhage