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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug 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
• Drug 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.

Primary outcome measures

• The modified Rankin Scale score at 90 days post-treatment [Time frame: 90 days post-treatment]

Secondary outcome measures (10)

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

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

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• Teasdale G, Maas A, Lecky F, Manley G, Stocchetti N, Murray G. The Glasgow Coma Scale at 40 years: standing the test of time. Lancet Neurol. 2014 Aug;13(8):844-54. doi: 10.1016/S1474-4422(14)70120-6. PMID 25030516
• Society Of Critical Care Medicine Chinese Medical Association. [Guidelines for analgesia and sedation treatment in intensive care unit of Chinese adults]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2018 Jun;30(6):497-514. doi: 10.3760/cma.j.issn.2095-4352.2018.06.001. No abstract available. Chinese. PMID 30009721
• Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, Tunn R, Aggarwal R, Berkwits M, Berlin JA, Bhandari N, Butcher NJ, Campbell MK, Chidebe RCW, Elbourne D, Farmer A, Fergusson DA, Golub RM, Goodman SN, Hoffmann TC, Ioannidis JPA, Kahan BC, Knowles RL, Lamb SE, Lewis S, Loder E, Offringa M, Ravaud P, Richards DP, Rockhold FW, Schriger DL, Siegfried NL, Staniszewska S, Taylor RS, T PMID 40228833
• Liu GG, Wu H, Li M, Gao C, Luo N. Chinese time trade-off values for EQ-5D health states. Value Health. 2014 Jul;17(5):597-604. doi: 10.1016/j.jval.2014.05.007. Epub 2014 Jul 23. PMID 25128053
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• Brott T, Adams HP Jr, Olinger CP, Marler JR, Barsan WG, Biller J, Spilker J, Holleran R, Eberle R, Hertzberg V, et al. Measurements of acute cerebral infarction: a clinical examination scale. Stroke. 1989 Jul;20(7):864-70. doi: 10.1161/01.str.20.7.864. PMID 2749846
• Saver JL. Optimal end points for acute stroke therapy trials: best ways to measure treatment effects of drugs and devices. Stroke. 2011 Aug;42(8):2356-62. doi: 10.1161/STROKEAHA.111.619122. Epub 2011 Jun 30. PMID 21719772

Identifiers

NCT: NCT07695220 · 2026SMU017

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗