Blood Pressure After Endovascular Stroke Therapy-II

Phase 2

Completed

Conditions: Endovascular Thrombectomy
Acute Stroke

Interventions: Drug: Nicardipine
Drug: Labetalol
Drug: Hydralazine

Registration Number: NCT04116112

Lead Sponsor: University of Cincinnati

Brief Summary: The purpose of this study is to assess the safety of lowering blood pressure in acute stroke patients that are successfully treated with a mechanical thrombectomy procedure. The investogators will evaluate the hypothesis that lower blood pressure management strategies do not result in larger volume of stroke or worse 3-month clinical outcome in these patients.

Detailed Description: Several thousand patients suffer from an ischemic stroke caused by an occlusion of a large blood vessel supplying the brain. Endovascular mechanical thrombectomy (EVT) has revolutionized management of this most devastating type of ischemic stroke by allowing removal of the occlusive clot. However, about half of the successfully EVT-treated patients (\~85% of all treated patients) still remain disabled at 90 days. Early evidence suggests that patients with lower blood pressure (BP) after the thrombectomy procedure have better outcomes. However, safety of lowering BP in these patients has not been determined. The primary safety concern of lowering BP comes from the potential of compromising blood flow to the "at risk" area of the brain following the stroke.

The purpose of this trial is to evaluate the safety of lower BP management strategies in patients who are successfully treated with endovascular treatment for ischemic stroke. The investigator will enroll 120 individuals who qualify and randomly assign them to one of the three systolic BP (SBP) targets: ≤180 mmHg, \<160 mmHg, and \<140 mmHg (40 patients in each group). Treatment will begin soon after the blood clot causing the stroke is removed, using anti-hypertensive medication given intravenously with a goal to lower and maintain the SBP below assigned target for 24 hrs.

The scientists will assess the safety of lower BP targets (\<160 mmHg and \<140 mmHg) by quantifying the volume of stroke measured with an MRI scan obtained at 36+/-12 hours and participants' functional status at 90 days measured with a patient centered disability score. Participants will undergo the 36 +/-12-hour MRI scan as part of their routine clinical care and will not be asked to prolong their hospital stay for study purpose. A phone interview will take place to determine their functional status at 90-days.

Enrollment of 120 patients will provide 80% power to detect a 10 cubic centimeter increase in stroke volume and a 0.10 decrease in utility-weighted modified Rankin score (a patient-centered disability score) for every 20 mmHg decrease in SBP. An interim analysis will be conducted after enrollment of 60 patients at which time the study may stop for safety concerns.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Adult patients (≥18 years)
Undergoing successful EVT (defined as modified Thrombolysis in Cerebral Ischemia Score, mTICI, ≥2b) for an occlusion in the anterior cerebral circulation large vessel (internal carotid artery and M1 or M2 segments of the middle cerebral artery).
Intervention will be initiated only for those with a successful recanalization (modified Thrombolysis in Cerebral Ischemia Score ≥ 2b).
Undergoing a baseline CT or MR perfusion study
Those with unsuccessful recanalization (mTICI 0-2a) will be not intervened upon.

Exclusion Criteria

Known heart failure with ejection fraction <30%
Presence of a left ventricular assist device
Patients undergoing extracorporeal membrane oxygenation
Pregnancy
Enrollment in any other clinical trial

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Higher Systolic Blood Pressure (SBP) Target	Nicardipine	Lower systolic blood pressure to ≤180 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain ≥160 mmHg.
Higher Systolic Blood Pressure (SBP) Target	Labetalol	Lower systolic blood pressure to ≤180 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain ≥160 mmHg.
Lower SBP (<160 mmHg) Target	Labetalol	Lower systolic blood pressure to \<160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>140 mmHg.
Higher Systolic Blood Pressure (SBP) Target	Hydralazine	Lower systolic blood pressure to ≤180 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain ≥160 mmHg.
Lower SBP (<160 mmHg) Target	Nicardipine	Lower systolic blood pressure to \<160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>140 mmHg.
Lower SBP (<160 mmHg) Target	Hydralazine	Lower systolic blood pressure to \<160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>140 mmHg.
Lower SBP (<140mmHg) Target	Labetalol	Lower systolic blood pressure to \<140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>110 mmHg.
Lower SBP (<140mmHg) Target	Nicardipine	Lower systolic blood pressure to \<140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>110 mmHg.
Lower SBP (<140mmHg) Target	Hydralazine	Lower systolic blood pressure to \<140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain \>110 mmHg.

Primary Outcome Measures

Name	Time	Method
Final Infarct Volume	36 (+/-12) hrs after treatment initiation	Infarct volume on diffusion-weighted MRI (or CT if MRI cannot be obtained) at 36 (+/-12) hrs after treatment initiation, adjusted for the baseline CT perfusion core infract volume.
Utility-weighted Modified Rankin Score	90 days after treatment initiation	Modified Rankin score (mRS) is a scale for measuring the degree of disability or dependence of people who have suffered a stroke. 0 - no symptoms at all; 1 - no significant disability despite symptoms; able to carry out all usual duties and activities; 2- slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance; 3- moderate disability; requiring some help, but able to walk without assistance; 4 - moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance; 5 - severe disability; bedridden, incontinent and requiring constant nursing care and attention; 6- dead. Patient centered utility weights are applied to these scores as 1.0 for mRS level 0; 0.91 for mRS level 1; 0.76 for mRS level 2; 0.65 for mRS level 3; 0.33 for mRS level 4; 0 for mRS level 5; and 0 for mRS level 6. Unlike the mRS, the utility-weighted mRS runs from 0 to 1, with 0 being the worst.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Neurological Worsening Associated With Antihypertensive Treatment	Treatment initiation to 24 hrs after treatment initiation	Defined as number of participants with 4 points of greater increase in NIH Stroke scale associated with reduction in SBP caused by anti-hypertensive treatment initiation or titration.
Number of Participants With Symptomatic Hemorrhagic Transformation	36(+/-12) hrs after treatment initiation	Defined as number of participants with any new bleeding within the infarcted brain tissue and an NIH Stroke Scale worsening of 4 or more points associated with the bleeding within 36 (+/-12) hrs of treatment initiation
Number of Participants With Any Hemorrhagic Transformation	36(+/-12) hrs after treatment initiation	Number of participants with any new bleeding within the infarcted brain tissue on 36(+/-12) hr MRI/CT scan after treatment initiation

Trial Locations

Locations (3): Hartford Healthcare
🇺🇸
Hartford, Connecticut, United States
University of Cincinnati
🇺🇸
Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States