Outcome in Patients Treated With Endovascular Thrombectomy - optIMAL Blood Pressure Control 2 (OPTIMAL-BP 2)

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат BP lowering drugs (nicardipine, labetalol, urapidil)
  After successful reperfusion, appropriate antihypertension medication is administered to control systolic blood pressure \<180 mmHg.
• Препарат BP 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.

Первичные конечные точки

• Functinal independence [Срок оценки: 3 months]
• Symptomatic Intracranial Hemorrhage (sICH) [Срок оценки: 36 hours]
• Stroke related death [Срок оценки: 3 months]

Вторичные конечные точки (12)

• Shift analysis of mRS score distribution. [Срок оценки: 3 months]
• NIHSS score at 24 hours after endovascular treatment. [Срок оценки: 24 hours]
• Major Neurological Improvement at 24 hours, defined as either an NIHSS score of 0-1 or an improvement of 8 or more points. [Срок оценки: 3 months]
• Sustained vessel recanalization on CTA/MRA at 24 hours [Срок оценки: Discharge and 1 month]
• Proportion of functional independence at 1 month. [Срок оценки: 3 months]
• Differences in Euro-Q5 instrument. [Срок оценки: 36 hours to 1 week]
• Incidence of malignant cerebral edema. [Срок оценки: 36 hours]
• Infarction volumes [Срок оценки: 36 hours]
• Using intravenous BP lowering drug [Срок оценки: 3 months]
• Medication induced BP drop [Срок оценки: 3 months]
• Collateral circulation measured by Tan scale (good collateral is defined as Tan scale 2-3) in baseline CTA. [Срок оценки: 3 months]
• Variability in blood pressure (e.g., standard deviation, coefficient of variation, VIM, successive variation, and threshold). [Срок оценки: 3 months]

Критерии участия

<Inclusion Criteria>

• Age ≥20 years
• Acute ischemic stroke patients who underwent intraarterial thrombectomy for large vessel occlusion. (ICA, M1, M2, A1, P1, VA and BA)
• Patients with successful recanalization after intraarterial thrombectomy (TICI 2b or TICI 3)
• Patients with sustained systolic blood pressure (SBP) <150 mm Hg on successive measurements obtained less than 10 minutes apart within 3 hours after reperfusion.
• Patients with mean SBP <150 mmHg within 2 hours after successful recanalization (two measurements ≥2 minutes apart).

<Exclusion Criteria>

• Age <20
• Patients who failed recanalization of the intracranial artery after endovascular thrombectomy (modified TICI ≤ 2a).
• Patients with systolic blood pressure ≥ 150 mmHg after successful recanalization.
• 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.
• Patients who developed symptomatic intracranial hemorrhage before study enrollment, after successful recanalization.
• Patients with contraindications to Phenylephrine.
• Patients with contraindications to antihypertensive medications.
• Patients with pre-stroke functional disability (modified Rankin Scale, mRS ≥3).
• Patients with heart failure and reduced cardiac output, with an ejection fraction (EF) <40%.
• Patients with end-stage renal disease requiring renal replacement therapy, or chronic kidney disease stage 4 with an eGFR <30 mL/min.
• Patients currently taking monoamine oxidase (MAO) inhibitors.
• Patients with persistent bradycardia with a heart rate <45 bpm.
• Pregnant patients.
• 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.
• Patients who do not consent to participate in the study.
• Patients participating in another study that does not allow co-enrollment.
• Patients whom the investigator deems unsuitable for study participation for any reason.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Department of Neurology, Yonsei University College of Medicine — Seoul

Идентификаторы

NCT: NCT06677970 · 4-2024-0880

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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