REmifentanil And Dexmedetomidine for EarlY Intensive Blood Pressure Lowering in ICH.

Официальное название

Efficacy and Safety of an Early Intensive Blood Pressure-Lowering Strategy Using Remifentanil and Dexmedetomidine in Patients With Spontaneous Intracerebral Hemorrhage: A Multicenter, Prospective, Superiority, Randomized Controlled Trial

Обзор

Intracerebral hemorrhage (ICH) remains the most devastating subtype of stroke, with a case fatality rate of approximately 40% at one months post-onset, imposing a particularly heavy medical and economic burden on low- and middle-income countries. Studies have shown that poor prognosis in ICH patients is associated with acute blood pressure elevation and hematoma expansion after onset. Blood pressure control during the acute phase is considered a potentially key therapeutic strategy for improving outcomes in ICH patients; however, no clinical study has yet demonstrated a clear advantage of any specific antihypertensive agent or combination. Previous researchers have confirmed that the combined use of remifentanil and dexmedetomidine, while providing effective analgesia, sedation, and anti-sympathetic effects, could reduce dramatic fluctuations in blood pressure and heart rate, thereby facilitating more stable blood pressure reduction and potentially further improving functional outcomes in ICH patients. The investigators plan to conduct a multicenter, prospective, randomized controlled, superiority clinical trial within mainland China to evaluate the efficacy and safety of an early intensive blood pressure-lowering strategy using remifentanil combined with dexmedetomidine for improving functional prognosis in acute ICH patients. This study aims to provide evidence-based medical support for the use of remifentanil combined with dexmedetomidine in early intensive blood pressure-lowering in patients with ICH, to enrich the available options for early intensive blood pressure-lowering strategies, to improve the adverse prognosis of patients.

Подробное описание

Spontaneous intracerebral hemorrhage refers to non-traumatic bleeding within the brain parenchyma caused by the rupture of large or small arteries, veins, or capillaries, which may secondarily extend into the ventricles or subarachnoid space. As one of the most devastating subtypes of stroke, intracerebral hemorrhage has a 30-day mortality rate of approximately 40%, with only 12-39% of patients regaining functional independence. Studies have shown that poor outcomes in intracerebral hemorrhage patients are closely associated with acute elevated blood pressure and hematoma expansion after onset, highlighting the urgent need to optimize clinical interventions. Therefore, understanding the pathophysiological mechanisms of acute blood pressure changes in intracerebral hemorrhage and refining early intensive antihypertensive strategies are of great clinical importance for improving patient outcomes. Previous researchers have demonstrated that a remifentanil and dexmedetomidine-based antihypertensive strategy enables rapid and stable blood pressure reduction. The investigators now intend to further investigate the efficacy and safety of this regimen compared to guideline-based standard treatment in improving patient outcomes.

This multi-center, prospective, open-label, randomized controlled, superiority clinical trial will be planned to be conducted in mainland China. It will primarily enroll patients with acute intracerebral hemorrhage who present within 6 hours of symptom onset and have an initial systolic blood pressure of 150 mmHg or higher. Patients will be excluded if they have contraindications to urgent intensive blood pressure-lowering therapy, if the hemorrhage is secondary to other etiologies, or if they have a high risk of death within 24 hours. Based on sample size calculation, a total of 1,116 patients with acute intracerebral hemorrhage will be enrolled and allocated in a 1:1 ratio to either the intervention group or the control group through randomization. Participants assigned to the control group will receive conventional treatment according to the "Guidelines for the Management of Spontaneous Intracerebral Hemorrhage" published by the American Heart Association and the American Stroke Association. Participants assigned to the intervention group will receive early intensive blood pressure-lowering therapy with remifentanil combined with dexmedetomidine, in addition to the guideline-based standard treatment. Specifically, remifentanil and dexmedetomidine will be administered as soon as possible within 30 minutes after enrollment. The primary outcome measure of this study is the modified Rankin Scale score at 90 days after treatment. Secondary outcome measures include blood pressure and blood glucose levels during the treatment period, the incidence of hematoma expansion, and the length of stay in the intensive care unit, among others. The results of this study are expected to fill the evidence gap regarding specific antihypertensive combinations in improving functional outcomes, and to provide high-quality evidence for future guideline updates.

Вмешательства

• Препарат Remifentanil and Dexmedetomidine
  Participants will receive remifentanil and dexmedetomidine within 30 minutes after treatment initiation, and the treatment will be continued for 7 days or until discharge from the intensive care unit. The starting dose of remifentanil is 0.025 μg/kg/min, which will be adjusted during infusion based on the patient's blood pressure and analgesic requirements. For non-mechanically ventilated patients, the dose adjustment range is 0.025-0.05 μg/kg/min; for mechanically ventilated patients, the dose
• Препарат Guideline standard care
  Participants will receive conventional treatment in accordance with the "Guidelines for the Management of Spontaneous Intracerebral Hemorrhage" published by the American Heart Association and the American Stroke Association.

Первичные конечные точки

• The modified Rankin Scale score at 90 days post-treatment [Срок оценки: 90 days post-treatment]

Вторичные конечные точки (10)

• Poor Functional Outcome [Срок оценки: 90 days post-treatment]
• Blood Pressure Management [Срок оценки: 24 hours, 3 days, and 7 days post-treatment]
• Glycemic Control [Срок оценки: 24 hours, 3 days, and 7 days post-treatment]
• National Institutes of Health Stroke Scale [Срок оценки: 7 days]
• Glasgow Coma Scale [Срок оценки: 7 days]
• Hematoma Expansion [Срок оценки: 24 hours and 7 days]
• Quality of Life Assessment [Срок оценки: 90 days]
• Duration of Mechanical Ventilation [Срок оценки: 7 days]
• Intensive care unit Length of Stay [Срок оценки: 7 days]
• Hospitalization Status at 90 Days [Срок оценки: 90 days]

Критерии участия

Критерии включения

• Age ≥ 18 years.
• Acute intracerebral hemorrhage confirmed by non-contrast head computed tomography.
• Symptom onset ≤ 6 h before randomization.
• At least two systolic blood pressure ≥ 150 mmHg separated by > 2 min prior to randomization.
• Admission to a monitored unit capable of active acute care (e.g., acute stroke unit, emergency department, or intensive care unit).
• Written informed consent provided by the patient or legally authorized representative.

Критерии исключения

• Contraindication to intensive blood-pressure lowering (e.g., severe stenosis of carotid, vertebral, or cerebral arteries; Moyamoya disease; Takayasu arteritis; critical aortic stenosis).
• Clear evidence that the hemorrhage is secondary to a structural brain abnormality (arteriovenous malformation, aneurysm, tumor, trauma, infarct) or recent thrombolysis.
• Ischemic stroke within the preceding 30 days.
• Very high probability of death within 24 h based on clinical and/or radiologic criteria.
• Known advanced dementia or pre-stroke disability (pre- modified Rankin Scale score ≥ 3).
• Coagulopathy due to medication or hematologic disorder.
• Comorbid conditions that would interfere with outcome assessment or follow-up (e.g., active malignancy, end-stage organ failure).
• Known hypersensitivity to remifentanil or dexmedetomidine.
• Pregnancy or lactation.
• Concurrent participation in another investigational drug or device trial.
• Patient or legally authorized representative unwilling or unable to provide informed consent, or judged unlikely to comply with study procedures or follow-up.

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

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

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Идентификаторы

NCT: NCT07695220 · 2026SMU017

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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