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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.