Acute Ischemic Stroke
Conditions
Keywords
Blood pressure, Ischemic stroke, thrombectomy, outcome
Brief summary
Though intravenous thrombolysis has been shown to improve symptoms in acute ischemic stroke patients, the recanalization rate remains low (22.6%) and only around 30% of patients benefit from the treatment. Recently, endovascular thrombectomy using stent retrievers or catheters has proven to be more effective, with a success rate of nearly 80%. However, only 50% of patients experience clinical improvement, highlighting the need for new treatment strategies to enhance outcomes. Current guidelines recommend maintaining systolic blood pressure (BP) below 180 mmHg after thrombectomy, but there is a lack of evidence regarding optimal blood pressure management post-reperfusion. Four randomized clinical trials, including the OPTIMAL-BP trial, have examined blood pressure control following thrombectomy. Meta-analyses showed that intensive BP lowering did not reduce symptomatic hemorrhage and was associated with worse functional outcomes at 3 months. Specifically, lowering BP too aggressively after successful reperfusion could worsen outcomes by reducing perfusion to the ischemic penumbra. Therefore, this study will investigate whether a more targeted blood pressure elevation strategy could improve patient prognosis compared to standard BP control in patients with sustained systolic blood pressure (SBP) \<150 mmHg on successive measurements obtained less than 10 minutes apart within 3 hours after reperfusion. This is a prospective, randomized, open-label trial with blinded endpoint assessment (PROBE) design, aimed at comparing intensive and standard BP control strategies in acute ischemic stroke patients. Participants will be randomized 1:1 into either an intensive BP control group (targeting a 20% systolic BP increase, capped at less than 160 mmHg) or a standard BP control group (systolic BP at or below 180 mmHg).
Detailed description
1. This is a prospective, randomized, open-label trial with blinded endpoint assessment (PROBE) design. 2. Participants will be randomly assigned in a 1:1 ratio to either an intensive BP control group (targeting a 20% increase from baseline systolic BP, capped at less than 160 mmHg) or a standard BP control group (maintaining systolic BP at or below 180 mmHg). 3. Randomization: Allocation will be stratified by stroke severity (NIHSS \<15 or ≥15) and participating study center. Randomization will be conducted via a web-based system using a pre-generated randomization table created by a statistician. Investigators will enter stratification variables (study center, NIHSS score) into the system to receive the randomized allocation. 4. This is a multi-center prospective study involving patients admitted to participating hospitals for acute ischemic stroke between October 2024 and December 2029 (last visit date). The study will include patients who undergo successful intra-arterial reperfusion therapy based on current stroke guidelines. 5. Data collection will include the medical history, imaging findings, BP parameters (systolic BP, diastolic BP, BP variability), neurological scores, functional recovery, and quality of life (QoL) measures for eligible participants. 6. Neurological scores, functional recovery, and QoL assessments will be conducted by independent evaluators who are blinded to treatment allocation. 7. All data will be collected using electronic case report forms (e-CRF), and anonymized imaging data will be sent to the coordinating center. 8. The coordinating center will perform blinded quantification of imaging results.
Interventions
DRUGBP lowering drugs (nicardipine, labetalol, urapidil)
After successful reperfusion, appropriate antihypertension medication is administered to control systolic blood pressure \<180 mmHg.
DRUGBP raising drug (phenylephrine) or BP lowering drugs (nicardipine, labetalol, urapidil)
After successful reperfusion, appropriate BP raising (20% increase in SBP, maximum of 160 from baseline SBP) are administered.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
The mRS scores and adverse events were determined in participants at 1 month and 3 months via telephone or in person by local certified medical staff who were blinded to the treatment allocation.
Intervention model description
a multicenter, randomized, open Lable, blinded end-point clinical trial.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\<Inclusion Criteria\> 1. Age ≥20 years 2. Acute ischemic stroke patients who underwent intraarterial thrombectomy for large vessel occlusion. (ICA, M1, M2, A1, P1, VA and BA) 3. Patients with successful recanalization after intraarterial thrombectomy (TICI 2b or TICI 3) 4. Patients with sustained systolic blood pressure (SBP) \<150 mm Hg on successive measurements obtained less than 10 minutes apart within 3 hours after reperfusion. 5. Patients with mean SBP \<150 mmHg within 2 hours after successful recanalization (two measurements ≥2 minutes apart). \<
Exclusion criteria
\> 1. Age \<20 2. Patients who failed recanalization of the intracranial artery after endovascular thrombectomy (modified TICI ≤ 2a). 3. Patients with systolic blood pressure ≥ 150 mmHg after successful recanalization. 4. Patients unable to receive antihypertensive medication post-thrombectomy or in whom the investigator believes aggressive blood pressure control could have adverse effects, such as increased risk of hemorrhage. 5. Patients who developed symptomatic intracranial hemorrhage before study enrollment, after successful recanalization. 6. Patients with contraindications to Phenylephrine. 7. Patients with contraindications to antihypertensive medications. 8. Patients with pre-stroke functional disability (modified Rankin Scale, mRS ≥3). 9. Patients with heart failure and reduced cardiac output, with an ejection fraction (EF) \<40%. 10. Patients with end-stage renal disease requiring renal replacement therapy, or chronic kidney disease stage 4 with an eGFR \<30 mL/min. 11. Patients currently taking monoamine oxidase (MAO) inhibitors. 12. Patients with persistent bradycardia with a heart rate \<45 bpm. 13. Pregnant patients. 14. Patients with severe medical or surgical comorbidities, including but not limited to: terminal cancer with life expectancy \<6 months, severe cardiac or aortic disease, severe hematologic disorders, advanced chronic heart failure, severe pneumonia, or sepsis. 15. Patients who do not consent to participate in the study. 16. Patients participating in another study that does not allow co-enrollment. 17. Patients whom the investigator deems unsuitable for study participation for any reason.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functinal independence | 3 months | Proportion of patients with a functional independence (defined as mRS ≤ 2) at 3 months, assessed using the modified Rankin Scale (mRS). |
| Symptomatic Intracranial Hemorrhage (sICH) | 36 hours | Symptomatic Intracranial Hemorrhage (sICH) after Endovascular Treatment Intracranial hemorrhage or hemorrhagic transformation identified on MRI (GRE or SWI) or CT within 24 ± 12 hours or due to clinical worsening. (Symptomatic intracranial hemorrhage is defined according to the European Cooperative Acute Stroke Study III \[ECASS III\] criteria) |
| Stroke related death | 3 months | Stroke related death within 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Shift analysis of mRS score distribution. | 3 months | Distributional analysis of the modified Rankin Scale (mRS) scores to assess overall functional outcome shift between treatment groups. |
| NIHSS score at 24 hours after endovascular treatment. | 24 hours | Difference in National Institutes of Health Stroke Scale (NIHSS) scores between at 24 hours post-EVT. |
| Major Neurological Improvement at 24 hours, defined as either an NIHSS score of 0-1 or an improvement of 8 or more points. | 3 months | Proportion of patients achieving substantial neurological recovery within 24 hours after EVT. |
| Sustained vessel recanalization on CTA/MRA at 24 hours | Discharge and 1 month | Evaluation of angiographic reperfusion status (modified Thrombolysis in Cerebral Infarction \[mTICI\] grade ≥2b) |
| Proportion of functional independence at 1 month. | 3 months | Percentage of patients achieving mRS 0-2 at 1 month. |
| Differences in Euro-Q5 instrument. | 36 hours to 1 week | Differences in scores measured by Euro-Q5 scale. |
| Incidence of malignant cerebral edema. | 36 hours | Frequency of radiologically or clinically confirmed malignant cerebral edema after EVT. |
| Infarction volumes | 36 hours | Proportion of functional independence according to infarction volumes in DWI |
| Using intravenous BP lowering drug | 3 months | Proportion of functional independence according to intrvenous BP lowering drug |
| Medication induced BP drop | 3 months | Proportion of functional independence according to medication inuced BP drop |
| Collateral circulation measured by Tan scale (good collateral is defined as Tan scale 2-3) in baseline CTA. | 3 months | Proportion of functional independence according to the degree of collateral flow |
| Variability in blood pressure (e.g., standard deviation, coefficient of variation, VIM, successive variation, and threshold). | 3 months | Evaluation of outcome associations with multiple BP variability indices |
| Outcome comparison by baseline ischemic core burden measured with ASPECTS. | 3 months | Proportion of functional independence according to the ASPECTS (Alberta Stroke Program Early CT Score) on CT or MRI. |
| Evaluation of differential outcomes in patients who received IV tPA before EVT. | 3 months | Proportion of functional independence according to prior tPA administration. |
| Comparison of outcomes according to presence or severity of intracranial atherosclerotic stenosis. | 3 months | Proportion of functional independence according to intracranial arterial stenosis. |
| Assessment of outcome differences by number of thrombectomy passes. | 3 months | Proportion of functional independence according to multiple attempts at endovascular recanalization. |
| Evaluation of outcomes relative to attainment and timing of post-EVT BP target. | 3 months | Proportion of functional independence according to achieving the target blood pressure and the time to target on outcomes. |
| Outcome comparison by initial angiographic reperfusion grade before BP intervention. | 3 months | Proportion of functional independence according to baseline mTICI scores. |
| Assessment of outcome differences between patients with and without early neurological worsening. | 3 months | Proportion of functional independence according to neurological deterioration (NIHSS worsening by ≥4 points). |
| Evaluation of outcomes stratified by occlusion site (e.g., ICA, M1, M2). | 3 months | Proportion of functional independence according to the occluded vessel involved. |
| Biochemical markers including D-dimer, CRP, or glucose | 3 months | Proportion of functional independence according to laboratory findings including D-dimer, CRP, or glucose. |
| Evaluation of vascular stiffness as a determinant of post-EVT outcomes. | 3 months | Proportion of functional independence according to estimated pulse wave velocity (ePWV). |
| Small artery disease - white matter hyperintensity | 3 months | Proportion of functional independence according to degree of white matter hyperintensity |
| Small artery disease - microbleeds | 3 months | Proportion of functional independence according to number of microbleeds |
| Small artery disease - old lacunar infarction | 3 months | Proportion of functional independence according to number of old lacunar infarctions |
| Optimal target BP according to AI predicting for functional independence in 10 mmHg increments | 3 months | Model-based identification of the optimal SBP target range predicted by AI for favorable outcomes. |
| Occurrence of adverse event or serious adverse event | 3 months | Incidence and type of adverse events |
| Treatment failure, defined as failure to achieve target blood pressure on two consecutive measurements within 24 hours after endovascular therapy. | 24 hours | Rate of unsuccessful BP target attainment during the acute post-procedure period. |
| Differences in BP variability depending on the antihypertensive agent use (labetalol or nicardipine). | 24 hours | Comparison of short-term BP stability between BP medication used for post-EVT management. |
| Differences in causes of death. | 3 months | Comparison of mortality causes |
| Diffrences in fuctional outcomes at 1 year. | 1 year | Difference in 1-year functional outcomes according to mRS and EQ-5D-5L. |
| Euro-Q5-5L analogue scale. | 1 year | Differnec in scores measured by Euro-Q5 scale. |
Countries
South Korea
Contacts
CONTACTHyo Suk Nam, MD,PhD
Outcome results
None listed