Design of the BEST‐II Randomized Clinical Trial

Authors: Eva A. Mistry, Kimberly Hart, Taylor Davis, Sharon Yeatts, Christopher J. Lindsell, Roger J. Lewis, Gregory Albers, Jonathan P. Wanderer, Charles Prestigiacomo, Gordon R. Bernard, Pooja Khatri

Abstract

Background

Prior observational studies indicate that lower systolic blood pressure (SBP) after successful endovascular treatment (EVT) is associated with better functional outcomes in patients with acute ischemic stroke. However, whether targeting SBP to levels below the guideline‐recommended target of ≤180 mm Hg is safe and efficacious remains to be determined.

Methods

The BEST (Blood Pressure After Endovascular Stroke Therapy)‐II trial (NCT04116112) is a pragmatic, phase 2, multisite, prospective, randomized, open‐label trial with blinded end‐point assessment designed to (1) compare the safety of lower SBP targets with higher SBP targets in successfully EVT‐treated patients with stroke and (2) inform the design and estimate the probability of success of a future phase 3 trial. A total of 120 patients with acute ischemic stroke who undergo successful EVT (final modified Thrombolysis in Cerebral Infarction score ≥2b) for intracranial internal carotid artery or M1 or M2 segment of the middle cerebral artery will be randomized to the SBP targets of ≤180, <160, and <140 mm Hg, to be maintained for 24 hours using intravenous nicardipine as the first‐line agent. We will assess the harm of decreased post‐EVT SBP by quantifying its linear relationship with multiple primary outcomes of final infarct volume on magnetic resonance imaging (or computed tomography) at 36 hours and utility‐weighted modified Rankin scale score at 90 days. The study is approved by the Institutional Review Boards of both participating institutions and the Data and Safety Monitoring Board.

Results

Enrollment in the BEST‐II trial began in January 2020, with 90 patients enrolled as of October 13, 2021. The trial is progressing ahead of target, with an anticipated enrollment completion date before January 2023.

Conclusions

The BEST‐II trial results will inform the stroke community of the safety of lower SBP targets in patients with acute ischemic stroke who are successfully treated with EVT and will demonstrate the feasibility of both achieving lower blood pressure targets as well as conducting an efficacy trial. Trial enrollment is on target despite the COVID‐19 pandemic.

Clinical Trial Registration Information

NCT04116112 (https://clinicaltrials.gov/ct2/show/NCT04116112)

Although endovascular clot retrieval treatment (endovascular thrombectomy [EVT]) is a highly effective treatment for patients with acute ischemic stroke (AIS), nearly 50% of patients who receive it will die or remain disabled at 90 days. ^1^ In addition to refinement of EVT technology, optimizing periprocedural and postprocedural management may help improve outcomes. An important and possibly neuroprotective intervention is blood pressure (BP) management following EVT. During reperfusion after transient large‐vessel occlusion in rodent models, cerebral arteries demonstrate impaired autoregulation and fail to maintain a constant cerebral blood flow over a wide range of systemic BP to prevent brain injury. ^2^ , ^3^ After a successful EVT for removal of a blood clot causing a large‐vessel occlusion, increased systolic BP (SBP) can lead to hyperperfusion injury, resulting in inflammation, reactive oxygen species generation, and hemorrhage. ^4^ Observational studies have demonstrated that lower SBP after successful EVT is associated with better functional outcomes in patients with AIS. ^5^ , ^6^ , ^7^ , ^8^ In our own observational study, we found that among EVT‐treated patients, those with good outcomes tended to have an SBP of <160 mm Hg in the first 24 hours post‐EVT, whereas those with poor outcomes experienced higher SBP in the 24 hours post‐EVT. ^9^ There is some concern that should the SBP be targeted toward a lower level after recanalization, hypoperfusion may occur, especially at the microcirculatory level. ^10^ This raises concerns for an increased infarct volume. ^11^ , ^12^

The 2019 American Heart Association/American Stroke Association and European Stroke Organization guidelines recommend lowering SBP to ≤180 mm Hg in the first 24 hours after an EVT based on conventions from prior trials of thrombolysis and EVT. ^13^ , ^14^ These guidelines allow for a higher than normal SBP, but without robust evidence, current SBP management remains heterogeneous. Practice across the United States deviates variably and widely from these guidelines. ^15^ An evidence base is needed to inform practice; the 2018 American Heart Association/American Stroke Association guideline committee and leaders of the Stroke Treatment Academic Industry Roundtable identified BP management as a premier question in stroke that needs an urgent answer. ^16^ , ^17^ , ^18^ One early randomized trial has shown no evidence that an SBP target of 130 mm Hg, compared with <185 mm Hg, reduces the rates of any radiographic intraparenchymal hemorrhage after successful EVT. ^19^ Further trials are needed to evaluate the risk for hypoperfusion with lower SBP targets and the impact of different SBP targets on clinically relevant outcomes. Such information will allow the selection of an optimal SBP target that balances newly known risks and benefits of aiming too high or too low. Herein, we present the design and methodologic aspects of a randomized phase 2 trial designed to evaluate the safety and preliminary efficacy of lower SBP targets compared with higher targets in the first 24 hours post‐EVT in patients with AIS who have undergone successful endovascular recanalization. The goal of the study is to determine the appropriateness of proceeding to a phase 3 trial of a lower SBP target after successful EVT.

Methods

Study Setting

The BEST (Blood Pressure After Endovascular Stroke Therapy)‐II trial (NCT04116112) is designed as a pragmatic, phase 2, multisite, prospective, randomized, open‐label trial with blinded end point assessment (Prospective Randomized Open Label Blinded Endpoint) clinical trial. The central objectives of the trial are (1) to compare the safety of lower SBP targets with higher SBP targets in successfully EVT‐treated stroke patients and (2) to inform the design and estimate the probability of success of a future phase 3 trial.

Study Population

The inclusion criteria are as Adult patients (aged ≥18 years) with AIS.Receipt of successful EVT (defined as modified Thrombolysis in Cerebral Infarction ≥2b) for an occlusion in the intracranial anterior cerebral circulation large vessel (specifically, internal carotid artery and M1 or M2 segments of the middle cerebral artery, including M1 and M2 occlusions occurring in tandem with internal carotid artery occlusion).

Patients meeting the following criteria will be (1) a diagnosis of heart failure with ejection fraction <30%; (2) left ventricular assist device; and (3) extracorporeal membrane oxygenation. Patients are also excluded if informed consent cannot be obtained within 45 minutes of EVT recanalization. Pregnant women will be excluded as EVT practice in setting of pregnancy is heterogeneous and SBP targets may carry unknown risks in this population. Coenrollment is permitted if the principal investigators of both trials agree the study protocols will not interfere with each other or place the patient at additional risk.

The BEST‐II trial is a pragmatic clinical trial that has broad inclusion criteria. For example, baseline hypertension and end‐stage renal disease are not incorporated in the eligibility criteria. This design feature is purposefully implemented so that the results might inform a future pragmatic pivotal trial so that the conclusions can be applicable to the broadest patient population possible. Furthermore, presence or absence of baseline comorbidities is often not fully known in the acute stroke setting, where patients cannot provide medical history and surrogates are unavailable or unfamiliar with patients’ medical conditions. We outline our plans to undertake systematic analysis to uncover the differential effects of post‐EVT SBP targets on outcomes of these baseline variables in the statistical considerations below.

Study Procedures

Study workflow is detailed in Figure 1. Consecutive patients undergoing EVT will be screened by the local study personnel, identified using the stroke or EVT paging system. Patients meeting the study criteria will be approached for informed consent by the local study coordinators at each site. The BEST‐II trial will use a Research Electronic Data Capture (REDCap)‐based electronic consent form to facilitate remote consenting from legally authorized representatives, in addition to the traditional in‐person paper consent. Within 45 minutes of recanalization, consenting patients will be randomized to post‐EVT SBP targets of ≤180 mm Hg (current guideline recommended), <160 mm Hg, or <140 mm Hg using permuted block randomization, stratified by site, in 1:1 ratio.

SBP management is intended to be initiated within 60 minutes of final recanalization to maintain the SBP at or below the randomly assigned target for 24 hours. The use of antihypertensive agents to maintain SBP at or below the target will be protocolized with intravenous nicardipine recommended for use as the first‐line agent, at a starting dose of 2.5 mg/h and increased as necessary by 2.5 mg/h every 15 minutes up to a maximum dose of 15 mg/h. Intravenous labetalol is added if SBP continues to be above the target despite maximum dose of intravenous nicardipine. Intravenous hydralazine can be used as the third‐line agent to be added at the treating physician's discretion. The BP management protocol is outlined in the Supplemental Table S1. Last, to ensure patient safety, if the clinical team determines that the randomized SBP target is unsafe for the enrolled patient at any time during the intervention period, then they may change the SBP target to one that is deemed safe by clinical consensus. The rationale for the change in the SBP target and the new SBP target must both be documented. Participants for whom the target SBP was considered unsafe will be included in the analysis using an as assigned, or intent‐to‐treat, approach.

BP Monitoring

BP will be monitored noninvasively in a recumbent position using a BP cuff with the following minimum every 5 minutes for the first 15 minutes following nicardipine initiation or dose adjustment, then every 15 minutes for the first hour, followed by at least every 30 minutes until the end of 24 total hours after EVT. The treating physician may use an arterial line and more frequent BP measurements if clinically indicated. Study personnel will remotely monitor SBP values in real time during business hours (8 am–5 pm Monday to Friday), and at least 10% of the remaining hours (nights and weekends), to promote BP control at the assigned target. Study personnel will be instructed to provide prompt feedback to nurses and intensive care unit staff on out‐of‐range SBP values and the need for nicardipine titration.

Study Assessments

Enrolled patients’ history of baseline medical comorbidities, concomitant medications, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline modified Rankin scale (mRS) score, vital signs, and laboratory values will be obtained through a combination of direct patient interview and medical record review. The baseline imaging studies, including computed tomography (CT) of brain, CT angiogram of head and neck, and CT perfusion (not required), when performed as standard of care, will be obtained.

At 24 hours, the participant's NIHSS score will be assessed by a certified rater. Standard‐of‐care imaging will be obtained at 36 (±12) hours in the form of brain magnetic resonance imaging (MRI) and/or CT. Patients will be followed up at 90 (±14) days via an in‐person or telephone interview to ascertain mRS score by a blinded, certified rater.

A central, blinded review of imaging will be performed to ascertain the infarct volume on the 36±12 hour MRI (or CT scan if MRI is unavailable). Hemorrhage will be classified using the 36 (±12) hour CT scan, according to the ECASS (European Cooperative Acute Stroke Study)‐III criteria. Other imaging variables that will be centrally ascertained include the baseline Alberta Stroke Program Early CT score, location of vessel occlusion on CT angiogram, baseline core and penumbra volumes on CT perfusion (if available; defined as volume of cerebral blood volume <30% of the contralateral side and volume of Time‐to‐Maximum (Tmax) >6 seconds, respectively), baseline collateral grade scored on the modified Tan score, and hypoperfusion‐intensity ratio.

End Points

The study is designed to test for the possibility of harm using lower SBP targets. Harm may be quantified on imaging or measured as a clinical outcome. We have selected 2 primary end Final infarct volume (FIV) measured on the MRI of brain obtained at 36 (±12) hours (or CT scan if MRI cannot be obtained) by a central, blinded neuroradiologist.Utility‐weighted mRS (UW‐mRS) score. The mRS is measured at 90 (±14) days by a blinded, certified outcome assessor. The standard utility weights are applied to each mRS level. ^20^

Both of the primary end points will be tested for the evidence of harm. To maximize the sensitivity of the trial to detect harmful effect, the end points will be considered independently without adjustments for multiplicity.

Secondary end points include the Any intracerebral hemorrhage (ICH) on 36 (±12) hours CT (or MRI if CT is unavailable).Symptomatic ICH on 36 (±12 hours) CT (or MRI if CT is unavailable). Symptomatic ICH is defined as any ICH associated with ≥4 points increase from the baseline NIHSS score per the modified ECASS definition. ^21^

Feasibility of achieving and adhering to the SBP will be described on the basis of the maximum SBP measured during any hour from 2 to 24 hours posttreatment initiation.

Data Acquisition

The Vanderbilt University Medical Center will serve as the central data management center. An electric case report form will be generated using the REDCap platform with built‐in checks and queries. Data will be periodically queried for completeness and accuracy by the central data management team. Clinician‐validated BP data, which are entered by the bedside nursing staff per the study protocol from the electronic medical record system, will be collected.

Statistical Considerations

(Additional details in the Supplemental Material).

Statistical Hypotheses

Hypothesis A 10–cubic centimeter (cc) increase in the FIV is considered clinically meaningful and known to be associated with worse outcome. ^22^ A 10‐cc increase in FIV with each 20–mm Hg decrease in SBP equates to a slope of 0.5 of a linear regression of FIV with SBP. Therefore, the alternative hypothesis is that the slope of a linear relationship between SBP and FIV is numerically >0.5. Hence, a significant finding would be evidence that decreasing SBP increases FIV beyond a level that is considered safe, informing the lower limit for targeting SBP for testing in future trials (Figure 2).

Hypothesis We consider 0.10 decrease in the UW‐mRS score from 0 (worst outcome) to 1 (best outcome) as clinically meaningful. A 0.10 decrease on the UW‐mRS score for every 20–mm Hg decrease in SBP equates to a slope of −0.005 of a linear regression of UW‐mRS with SBP. Therefore, the alternative hypothesis is that the slope of a linear relationship between SBP and the UW‐mRS is numerically <−0.005 (ie, a larger negative slope). Hence, a significant finding would be evidence that decreasing SBP worsens UW‐mRS, also informing the lower limit for targeting SBP for testing in future trials (Figure 2).

Sample Size

The target sample size for the trial is 120 patients. This was determined by first calculating the SD of the difference in infarct volume from baseline to final for all participants of the endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE‐3) trial. We conservatively assumed that these values of the difference could collectively represent the residuals of a linear regression between SBP as an independent variable and FIV in the worst‐case scenario, in which FIV demonstrates no association with SBP values. The SD of residuals was 50 cc. Using previously published BEST‐I trial data (prospective, observational, multicenter trial), we estimated the slope for the linear relationship of SBP and the UW‐mRS. ^9^ From this model, we calculated the SD of residuals to be 0.37 and inflated this to 0.5 to be conservative. With 101 subjects total, we will have 80% power using a 1‐sided test with the level of significance, α of 0.05 to test both these hypotheses (Table 1). To account for up to 15% rate of loss to follow‐up for 90 (±14)‐day outcome, our final sample size was inflated to 120 patients. FIV and UW‐mRS will be treated as continuous variables with normal distribution. ^23^

Statistical Analysis Plan

The intention‐to‐treat population is defined as all randomized participants grouped according to their original SBP target allocation, and will be used for primary analysis.

The BEST‐II trial is designed to detect harm of the lower SBP targets. No efficacy analysis will be undertaken. Therefore, all statistical tests pertaining to the harm hypotheses will be 1‐tailed with an α to reject the null hypothesis set at 0.05. The use of a less stringent criterion for statistical significance (ie, versus 0.025 1‐tailed) is to maximize the ability to detect harm. The magnitude of the effects with CIs will also be reported to further describe the harm potential.

Descriptives

A consolidated standards of reporting trials diagram will be used to describe entry of participants into the trial. Baseline characteristics will be described for each treatment group as assigned; categorical variables will be expressed as frequencies and percentages, and quantitative variables will be expressed as means±SD or medians (interquartile range). Baseline characteristics will not be compared between treatment groups using statistical testing. Where appropriate, differences will be quantified with CIs.

Primary Analysis

A linear mixed‐effects model will be constructed to quantify the slopes of FIV and UW‐mRS for patients randomized to low (<140 and <160 mm Hg) and high (≤180 mm Hg) SBP targets. We will adjust FIV for baseline Alberta Stroke Program Early CT score, and we will adjust the UW‐mRS score for the baseline mRS score. Age, baseline NIHSS score, and baseline collateral circulation status will be included in models for both outcomes; site will be included as a random effect.

To most sensitively test for harm of the low SBP targets, no corrections will be made for multiple hypothesis testing. The BEST‐II trial is designed to detect harm of lowering SBP in successfully EVT‐treated patients with AIS. In this case, a type II error (failing to detect harm when it occurs) is more detrimental than a type I error (concluding harm when it does not occur). We will not correct for multiplicity to maintain power at the expense of a type I error.

Secondary, Exploratory, and Other Analyses

Logistic regression models for the outcomes of any ICH and symptomatic ICH will be constructed for the intention‐to‐treat population with assigned SBP target group as the main predictor. The regression models will be adjusted for age, baseline NIHSS score, and intravenous alteplase administration.

Differential effects of SBP targeting are possible. To test for this, for each outcome, the main model will be extended to include the interaction between SBP group assignment and the putative effect modifier. We will test for differential treatment effects by age (as continuous variable), baseline Alberta Stroke Program Early CT score, collateral grade, and modified Thrombolysis in Cerebral Infarction reperfusion grade. A formal subgrouping analysis will be undertaken if the interaction term has a P<0.2. An exploratory subgroup analysis according to antihypertensive use (yes or no) before admission will be undertaken regardless of strength of evidence. The authors acknowledge that the study is likely underpowered to detect such interactions.

Fidelity to the assigned intervention will be represented both graphically and numerically. We will generate temporal profile plots for each patient's observed SBP values (color coded according to assigned SBP groups) and by plotting average hourly SBP for each group against time. Furthermore, we will report the average time spent below target for each group and the number of antihypertensive agents used (percentage of patients on 1, 2, 3, or >3 antihypertensive agents during the study period).

The FIV may not be measurable on all participants, including participants who die. Death is not frequent after successful EVT within the 36‐hour window when FIV is obtained, but if it occurs we will consider using a linear regression model with FIV counted as “1 cc worse than worst” for patients who die before 36 hours. We do not intend to impute missing outcomes for this phase 2 trial. However, if outcomes are missing for >5% of cases in either group (ie, 5 or 6 cases), a sensitivity analysis will be conducted using multiple imputation with predictive mean matching to assign outcomes to participants. Missing covariates will be handled similarly.

Interim Analysis

A single interim analysis will be done after a completed follow‐up of 60 enrolled patients. The study will be terminated in favor of the alternative hypothesis evidence of harm for a P≤0.025 for a slope of <−0.5 for FIV or >0.005 for UW‐mRS. The trial will not be terminated early for efficacy. No correction for α (ie, α spending) will be made in the final analysis to maintain power for finding a harm signal.

Regulatory Considerations and Safety Monitoring

The study was approved by the Institutional Review Boards of all participating institutions and the Data and Safety Monitoring Board (DSMB) before commencement of the enrollment. All adverse events will be adjudicated by the respective study site principal investigator. Serious adverse events will be reported to the Institutional Review Board, National Institute of Neurological Disorders and Stroke, and DSMB within a prespecified time window. Furthermore, relatedness of adverse events will be determined by the study site principal investigator (and DSMB in the event of serious adverse events). The DSMB will be convened after 6 months of enrollment (or enrollment of 30 patients, whichever occurs first), after 60 patients have completed 90‐day follow‐up (to review interim analysis), and after 90 patients have completed 90‐day follow‐up to review enrollment progress and data and patient safety concerns.

Discussion

The BEST‐II trial will evaluate the safety of lower SBP targets in patients with AIS who are successfully treated with EVT. More important, it will guide the design of a pivotal efficacy trial of lower post‐EVT SBP targets by informing the choice of SBP targets and the expected distribution of outcomes.

BP targets in the setting of acute stroke without EVT have been widely studied in the past. Many randomized trials using various antihypertensive agents have been neutral or negative. For example, the CHIPPS (Controlling Hypertension and Hypotension Immediately Post‐Stroke) trial found no difference in the functional outcomes of patients with acute stroke with hypertension treated with labetalol, lisinopril, or placebo. ^24^ The studies using angiotensin receptor antagonists have largely suggested harmful effects on cerebral perfusion. ^23^ , ^25^ , ^26^ The recent phase 3 randomized‐controlled ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study) found a lower rate of ICH in patients randomized to the intensive BP lowering arm (target SBP 130–140 mm Hg after tPA [tissue‐type plasminogen activator]) when compared with patients treated with guideline‐recommended SBP goal of <180 mm Hg. ^27^ However, there was no difference in the primary outcome of global disability at 90 days. Consequently, BP management guidelines in setting of acute stroke without EVT have largely remained unchanged and continue to recommend permissive hypertension up to <220/120 mm Hg during the acute and subacute period (<180/105 mm Hg in the setting of intravenous thrombolysis). ^13^

Clarity on ideal BP management strategies post‐EVT is currently lacking, and a causal relationship between post‐EVT SBP and patient outcomes is yet to be established. Elevated BP occurs commonly in acute stroke, but it may be either a reactive phenomenon or an indicator of a larger stroke destined for worse outcomes. Ischemic brain tissue is vulnerable to changes in systemic BP because of the lack of arterial myogenic reactivity and cerebral autoregulation. ^3^ In this scenario, it is possible that both hyperperfusion related to higher SBP and hypoperfusion related to lower SBP may be detrimental in patients with acute stroke with large‐vessel occlusion, given the higher baseline brain infarct and penumbra at‐risk volumes. Thus, it is imperative to first determine whether lowering SBP after successful EVT below the current guideline‐recommended target of ≤180 mm Hg is safe. Then, the goldilocks SBP target (ie, not too high and not too low) can be safely pursued in further trials. There is a putative U‐shape relationship between SBP in the setting of acute stroke and patient outcomes. In our observational study, a post‐EVT SBP of about 160 mm Hg in the first 24 hours distinguished between EVT‐treated patients who have good versus bad functional outcomes. ^9^ Thus, a post‐EVT target SBP of ≤160 mm Hg was forwarded as one of the SBP target doses in the BEST‐II trial. Two large observational studies have shown that a post‐EVT SBP target of <120 mm Hg may be associated with slightly worse patient outcomes, and that a target SBP of <140 mm Hg is associated with the best outcomes in patients with stroke after a successful EVT. ^28^ , ^29^ Thus, an SBP target of <140 mm Hg was also advanced for testing in the BEST‐II trial. One of the objectives at the trial completion will be to determine what dose (SBP target) is most likely to optimize outcomes post‐EVT for further testing in a pivotal trial.

The recently published BP TARGET trial did not show that lower SBP target improved ICH rates among patient population similar to the population intended for the BEST‐II trial. ^19^ The BP TARGET trial was powered to detect an absolute 15% reduction in the rate of any ICH among patients randomized to the lower SBP target group compared with the higher target, who were hypothesized to have an ICH rate of 40%. The observed rate of ICH was 42% in the intensive SBP target group and 43% in the higher target group, with a risk difference of −1.1% (95% CI, −11.6 to 10.1). However, the impact of post‐EVT SBP modulation may not be limited to hemorrhagic complications. Animal studies have suggested effects that in transient middle cerebral artery occlusion rats who have higher post‐MCAO (middle cerebral artery occlusion) BP have higher infarct volumes and worse functional outcomes. ^30^ Furthermore, BP modulation in the critical post‐EVT period may be associated with neuroinflammation, nonhemorrhagic consequences, or hyperperfusion, increased cerebral edema, and ultimately worse functional outcomes. Thus, in the BEST‐II trial, we chose to study infarct volume and functional outcomes as the most physiologically representative and clinically relevant outcome measures.

The BEST‐II trial relies on pragmatic clinical trial procedures and study assessments, and interventions are largely considered standard of care for the enrolled patient population (based on our survey results that each of the SBP targets is practiced with near‐equal frequency across the United States for this patient population). Trial enrollment commenced just before the COVID‐19 pandemic on January 16, 2020. During the first wave of the pandemic in March to June 2020, the trial enrollment was limited to patients not primarily presenting with COVID‐19 complications for the safety of clinical and research staff. Trial enrollment is progressing on target and is anticipated to be completed ahead of the goal completion date of January 2023. After its organizational meeting, the DSMB has met twice and has not recommended any changes to the trial protocol and enrollment.

Conclusions

There is little evidence on the safety and efficacy of BP lowering in patients successfully treated with EVT with substantial heterogeneity in the current clinical practice. ^15^ The BEST‐II multisite, phase 2, prospective, randomized, open‐label, blinded end point clinical trial will assess the safety and preliminary efficacy of post‐EVT SBP targets of ≤180, <160, and <140 mm Hg in patients with acute stroke successfully treated with thrombectomy for an anterior circulation large‐vessel occlusion. The trial is progressing ahead of target, with an anticipated enrollment completion date before January 2023.

Sources of Funding

Dr Mistry receives funding from the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (K23NS113858) for the conduct of the BEST‐II (Blood Pressure After Endovascular Stroke Therapy) trial. Additional funding is received from the Vanderbilt University Medical Center and the University of Cincinnati. The REDCap database is funded by UL1 TR000445 from National Center for Advancing Translational Sciences/NIH. Dr Khatri's work on this study is supported by NIH/National Institute of Neurological Disorders and Stroke U24 NS107241.

Disclosures

Dr Khatri reports a grant from Cerenovus (investigator‐initiated trial) and fees from Bayer (national leader of trial), Lumosa (consultant), Basking Biosciences (scientific advisor), Diamedica as (scientific advisor), and UpToDate (author); all are outside the submitted work.

Supporting information