Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04116112
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : July 7, 2020
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Eva Mistry, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment Phase
Acute Stroke Endovascular Thrombectomy Drug: Nicardipine Drug: Labetalol Drug: Hydralazine Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Blood Pressure After Endovascular Stroke Therapy-II: A Randomized Trial
Actual Study Start Date : January 17, 2020
Estimated Primary Completion Date : March 30, 2023
Estimated Study Completion Date : March 30, 2023

Resource links provided by the National Library of Medicine


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Apresoline




Primary Outcome Measures :
  1. Final Infarct Volume [ Time Frame: 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.

  2. Utility-weighted modified Rankin Score [ Time Frame: 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 :
  1. Number of participants with any hemorrhagic transformation [ Time Frame: 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

  2. Number of participants with symptomatic hemorrhagic transformation [ Time Frame: 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

  3. Number of participants with neurological worsening associated with antihypertensive treatment [ Time Frame: 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.


Other Outcome Measures:
  1. Compliance Outcome [ Time Frame: Treatment initiation to 24 hrs after treatment Initiation ]
    Number of participants with an hourly maximum SBP above target from 2-24 hrs post treatment initiation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116112


Contacts
Layout table for location contacts
Contact: Eva Mistry, MBBS 615936006 eva.a.mistry@vumc.org

Locations
Layout table for location information
United States, Ohio
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45221
Contact: Hilary Perez         
United States, Tennessee
Vanderbilt Univeristy Medical Center Recruiting
Nashville, Tennessee, United States, 37212
Contact: Eva Mistry, MBBS    615-936-0060    eva.a.mistry@vumc.org   
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
Layout table for investigator information
Principal Investigator: Eva Mistry, MBBS Vanderbilt University Medical Center
Layout table for additonal information
Responsible Party: Eva Mistry, Assistant Professor, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT04116112    
Other Study ID Numbers: 191520
K23NS113858 ( U.S. NIH Grant/Contract )
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: July 7, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
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
Keywords provided by Eva Mistry, Vanderbilt University Medical Center:
Blood Pressure Control
Additional relevant MeSH terms:
Layout table for MeSH terms
Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Hydralazine
Labetalol
Nicardipine
Antihypertensive Agents
Vasodilator Agents
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic alpha-1 Receptor Antagonists
Adrenergic alpha-Antagonists
Calcium Channel Blockers
Membrane Transport Modulators
Calcium-Regulating Hormones and Agents