Acute StrokePhase 2BEST-IINCT04116112
Blood Pressure After Endovascular Stroke Therapy-II
A Phase 2 study testing Nicardipine, Labetalol and Hydralazine in people with Acute Stroke and Endovascular Thrombectomy, run by University of Cincinnati at 3 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Stroke, Endovascular Thrombectomy
- What is being tested?
- Nicardipine, Labetalol and Hydralazine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Jan 2020to 15 Dec 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Cincinnati
Cincinnati, Ohio, 45221
Hartford Healthcare
Hartford, Connecticut, 06103
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
About this study
Official title: 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.
Read the 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
- Being tested
- Nicardipine, Labetalol, Hydralazine
- Keywords
- Blood Pressure Control
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NicardipineDrug
Also called Cardene
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.
LabetalolDrug
If SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes.
HydralazineDrug
Also called Apresoline
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.
| Study group | Role | What they receive |
|---|---|---|
| Higher Systolic Blood Pressure (SBP) Target | Experimental | Lower systolic blood pressure to ≤180 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain ≥160 mmHg. Receives: Drug: Nicardipine; Drug: Labetalol; Drug: Hydralazine |
| Lower SBP (<160 mmHg) Target | Experimental | Lower systolic blood pressure to <160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >140 mmHg. Receives: Drug: Nicardipine; Drug: Labetalol; Drug: Hydralazine |
| Lower SBP (<140mmHg) Target | Experimental | Lower systolic blood pressure to <140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >110 mmHg. Receives: Drug: Nicardipine; Drug: Labetalol; Drug: Hydralazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 90 days after treatment initiation
Secondary outcomes (3)
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
Measured: 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
Measured: 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.
Measured: Treatment initiation to 24 hrs after treatment initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start17 Jan 2020
- Primary completion1 Jul 2022
- Study completion15 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute StrokeStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Vanderbilt University Medical Center
- Responsible party
- Principal investigator, Eva A. Mistry, University of Cincinnati
- Investigators
- Eva Mistry, MBBS, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04116112
- Sponsor's protocol ID
- 191520
- Other IDs
- K23NS113858
- Acronym
- BEST-II
- Status last verified
- Sep 2023
- First submitted
- 3 Oct 2019
- Last updated
- 12 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Mistry EA, Hart K, Davis T, Yeatts S, Lindsell CJ, Lewis RJ, Albers G, Wanderer JP, Prestigiacomo C, Bernard GR, Khatri P. Design of the BEST-II Randomized Clinical Trial. Stroke Vasc Interv Neurol. 2022 May 5;2(3):e000249. doi: 10.1161/SVIN.121.000249. eCollection 2022 May.
PubMed 41583626Mistry 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.
PubMed 37668620
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood Pressure After Endovascular Stroke Therapy-II: A Randomized Trial
- ClinicalTrials.gov ID
- NCT04116112
- Acronym / sponsor ID
- BEST-II / 191520
- Conditions
- Acute Stroke, Endovascular Thrombectomy
- Keywords
- Blood Pressure Control
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS), Vanderbilt University Medical Center
- Study start
- 17 Jan 2020 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 15 Dec 2022 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Posted 12 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Higher Systolic Blood Pressure (SBP) Target | Experimental | Drug: Nicardipine, Drug: Labetalol, Drug: HydralazineLower 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 | Experimental | Drug: Nicardipine, Drug: Labetalol, Drug: HydralazineLower systolic blood pressure to <160 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >140 mmHg. |
| Lower SBP (<140mmHg) Target | Experimental | Drug: Nicardipine, Drug: Labetalol, Drug: HydralazineLower systolic blood pressure to <140 mmHg and maintain for 24 hours. If anti-hypertensive medication used, then maintain >110 mmHg. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NicardipineAlso: CardeneIn 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. | Drug | Higher Systolic Blood Pressure (SBP) Target, Lower SBP (<140mmHg) Target, Lower SBP (<160 mmHg) Target |
| LabetalolIf SBP is above target despite maximum nicardipine infusion for 30 minutes, 10-20 mg of intravenous labetalol will be added every 15 minutes. | Drug | Higher Systolic Blood Pressure (SBP) Target, Lower SBP (<140mmHg) Target, Lower SBP (<160 mmHg) Target |
| HydralazineAlso: ApresolineIf 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. | Drug | Higher Systolic Blood Pressure (SBP) Target, Lower SBP (<140mmHg) Target, Lower SBP (<160 mmHg) Target |
Primary outcome
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.
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.
3 secondary outcomes
Number of Participants With Any Hemorrhagic Transformation
Time frame: 36(+/-12) hrs after treatment initiation
Number of Participants With Symptomatic Hemorrhagic Transformation
Time frame: 36(+/-12) hrs after treatment initiation
Number of Participants With Neurological Worsening Associated With Antihypertensive Treatment
Time frame: Treatment initiation to 24 hrs after treatment initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41583626Mistry EA, Hart K, Davis T, Yeatts S, Lindsell CJ, Lewis RJ, Albers G, Wanderer JP, Prestigiacomo C, Bernard GR, Khatri P. Design of the BEST-II Randomized Clinical Trial. Stroke Vasc Interv Neurol. 2022 May 5;2(3):e000249. doi: 10.1161/SVIN.121.000249. eCollection 2022 May.
- Derived from this study: PubMed 37668620Mistry 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eva Mistry, MBBS principal investigator
University of Cincinnati
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicardipine, Labetalol and Hydralazine in people with Acute Stroke and Endovascular Thrombectomy, run by University of Cincinnati at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Final Infarct Volume (time frame: 36 (+/-12) hrs after treatment initiation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04116112, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023; AzTrials last refreshed its copy on 6 Nov 2026.