Blood Pressure After Endovascular Stroke Therapy-II

NCT ID: NCT04116112

Last Updated: 2023-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-17
• Study Completion Date: 2022-12-15

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.

Conditions

Acute Stroke; Endovascular Thrombectomy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Nicardipine

Intervention Type: DRUG

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.

Labetalol

Intervention Type: DRUG

If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.

Hydralazine

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Nicardipine

Intervention Type: DRUG

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.

Labetalol

Intervention Type: DRUG

If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.

Hydralazine

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Nicardipine

Intervention Type: DRUG

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.

Labetalol

Intervention Type: DRUG

If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.

Hydralazine

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Cardene; Apresoline

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Vanderbilt University Medical Center

OTHER

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Eva A. Mistry

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eva Mistry, MBBS

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

Hartford Healthcare

Hartford, Connecticut, United States

University of Cincinnati

Cincinnati, Ohio, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Countries

United States

References

Mistry EA, Hart KW, Davis LT, Gao Y, Prestigiacomo CJ, Mittal S, Mehta T, LaFever H, Harker P, Wilson-Perez HE, Beasley KA, Krothapalli N, Lippincott E, Stefek H, Froehler M, Chitale R, Fusco M, Grossman A, Shirani P, Smith M, Jaffa MN, Yeatts SD, Albers GW, Wanderer JP, Tolles J, Lindsell CJ, Lewis RJ, Bernard GR, Khatri P. Blood Pressure Management After Endovascular Therapy for Acute Ischemic Stroke: The BEST-II Randomized Clinical Trial. JAMA. 2023 Sep 5;330(9):821-831. doi: 10.1001/jama.2023.14330.

Reference Type: DERIVED

PMID: 37668620 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

K23NS113858

Identifier Type: NIH

Identifier Source: secondary_id

View Link

191520

Identifier Type: -

Identifier Source: org_study_id