Blood Pressure After Endovascular Stroke Therapy-II (BEST-II)

Blood Pressure After Endovascular Stroke Therapy-II: A Randomized Trial

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.

Study Overview

• Status: Completed
• Conditions: Acute Stroke; Endovascular Thrombectomy
• Intervention / Treatment: Drug: Nicardipine; Drug: Labetalol; Drug: Hydralazine

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06103
      • Hartford Healthcare
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • University of Cincinnati
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Higher Systolic Blood Pressure (SBP) Target; Lower systolic blood pressure to ≤180 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain ≥160 mmHg.	Drug: Nicardipine; In the event where SBP values are above the randomly assigned target, intravenous nicardipine will be initiated at 2.5 mg/hr to lower the SBP. If SBP is still not reduced to below assigned target after 15 minutes, nicardipine dose will be increased by 2.5 mg/hr every 15 minutes until the target SBP or a maximum dose of 15 mg/hr is reached.; Other Names: Cardene; Drug: Labetalol; If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.; Drug: Hydralazine; If SBP remains unresponsive for 1 hr despite the use of maximum doses of nicardipine and labetalol, a Hydralazine will be added at the treating physician's discretion. Incidence of the latter scenario is anticipated to be exceedingly rare.; Other Names: Apresoline
Experimental: Lower SBP (<160 mmHg) Target; Lower systolic blood pressure to <160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >140 mmHg.	Drug: Nicardipine; In the event where SBP values are above the randomly assigned target, intravenous nicardipine will be initiated at 2.5 mg/hr to lower the SBP. If SBP is still not reduced to below assigned target after 15 minutes, nicardipine dose will be increased by 2.5 mg/hr every 15 minutes until the target SBP or a maximum dose of 15 mg/hr is reached.; Other Names: Cardene; Drug: Labetalol; If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.; Drug: Hydralazine; If SBP remains unresponsive for 1 hr despite the use of maximum doses of nicardipine and labetalol, a Hydralazine will be added at the treating physician's discretion. Incidence of the latter scenario is anticipated to be exceedingly rare.; Other Names: Apresoline
Experimental: Lower SBP (<140mmHg) Target; Lower systolic blood pressure to <140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >110 mmHg.	Drug: Nicardipine; In the event where SBP values are above the randomly assigned target, intravenous nicardipine will be initiated at 2.5 mg/hr to lower the SBP. If SBP is still not reduced to below assigned target after 15 minutes, nicardipine dose will be increased by 2.5 mg/hr every 15 minutes until the target SBP or a maximum dose of 15 mg/hr is reached.; Other Names: Cardene; Drug: Labetalol; If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.; Drug: Hydralazine; If SBP remains unresponsive for 1 hr despite the use of maximum doses of nicardipine and labetalol, a Hydralazine will be added at the treating physician's discretion. Incidence of the latter scenario is anticipated to be exceedingly rare.; Other Names: Apresoline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Final Infarct Volume	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.	36 (+/-12) hrs after treatment initiation
Utility-weighted Modified Rankin Score	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.	90 days after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Hemorrhagic Transformation	Number of participants with any new bleeding within the infarcted brain tissue on 36(+/-12) hr MRI/CT scan after treatment initiation	36(+/-12) hrs after treatment initiation
Number of Participants With Symptomatic Hemorrhagic Transformation	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	36(+/-12) hrs after treatment initiation
Number of Participants With Neurological Worsening Associated With Antihypertensive Treatment	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.	Treatment initiation to 24 hrs after treatment initiation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance Outcome	Number of participants with an hourly maximum SBP above target from 2-24 hrs post treatment initiation	Treatment initiation to 24 hrs after treatment Initiation

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Vanderbilt University Medical Center
• Investigators: Principal Investigator: Eva Mistry, MBBS, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2020
• Primary Completion (Actual): July 1, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 3, 2019
• First Posted (Actual): October 4, 2019

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: September 21, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Blood Pressure Control
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Sympathomimetics; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Labetalol; Nicardipine; Hydralazine
• Other Study ID Numbers: 191520; K23NS113858 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No