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| Name | Class |
|---|---|
| Shenzhen People's Hospital | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Guideline-based standard care using remifentanil and dexmedetomidine | Experimental | Based on the standard blood pressure treatment protocol from the 2022 American Heart Association/American Stroke Association "Guidelines for the Management of Spontaneous Intracerebral Hemorrhage," the administration of remifentanil and dexmedetomidine will be initiated within 1 hour after randomization. The treatment will be continued for 7 days, or until the patient is transferred out of the intensive care unit if this occurs before day 7. |
|
| Guideline-based standard care | Active Comparator | Management will follow the 2022 American Heart Association/American Stroke Association "Guidelines for the Management of Patients with Spontaneous Intracerebral Hemorrhage". |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remifentanil and Dexmedetomidine | Drug | 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 adjustment range is 0.025-0.15 μg/kg/min. The starting dose of dexmedetomidine is 0.2 μg/kg/h, which will be adjusted during infusion based on the patient's blood pressure and sedation requirements, with a dose adjustment range of 0.2-0.7 μg/kg/h. |
| Measure | Description | Time Frame |
|---|---|---|
| The modified Rankin Scale score at 90 days post-treatment | The modified Rankin Scale score at 90 days post-treatment will be analyzed as an ordinal outcome (scores 0-6). The modified Rankin Scale is a standardized global 7-level disability scale, where a score of 0 or 1 indicates a favorable outcome (no symptoms or no significant disability), scores 2-5 represent increasing levels of disability and dependency, and a score of 6 indicates death. | 90 days post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Poor Functional Outcome | A modified Rankin Scale score of 3-6 at 90 days is defined as a poor outcome, including death and severe disability. Death is defined as modified Rankin Scale 6, and severe disability is defined as modified Rankin Scale 3-5. Death and severe disability will be combined and reported as a composite poor outcome measure, and will also be analyzed separately. | 90 days post-treatment |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Rui Dong, MM | Contact | +86 -15622176026 | dongrui_0419@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Hong Yang, MD | The Third Affiliated Hospital of Southern Medical University | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32419182 | Background | Cro S, Morris TP, Kenward MG, Carpenter JR. Sensitivity analysis for clinical trials with missing continuous outcome data using controlled multiple imputation: A practical guide. Stat Med. 2020 Sep 20;39(21):2815-2842. doi: 10.1002/sim.8569. Epub 2020 May 17. | |
| 25030516 | Background | 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. |
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This study plans to make study protocol available to individuals or institutions in need after the completion of participant enrollment and data collation. Such requests can be made by contacting the principal investigator.
It is expected to be made available in June 2029 and will remain accessible for a period of 5 years.
Contacte to principal investigator.
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| ID | Term |
|---|---|
| D002543 | Cerebral Hemorrhage |
| ID | Term |
|---|---|
| D020300 | Intracranial Hemorrhages |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077208 | Remifentanil |
| D020927 | Dexmedetomidine |
| ID | Term |
|---|---|
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Guideline standard care | Drug | 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. |
|
| Blood Pressure Management | (1) 1-hour blood pressure control rate: Defined as at least twice systolic blood pressure measurements <140 mmHg within the first hour after treatment initiation. (2) Mean blood pressure values: The average blood pressure values within 24 hours, 3 days, and 7 days post-treatment will be calculated for each group using all available measurements. (3) Blood pressure variability: Coefficient of Variation and Average Real Variability will be calculated based on all blood pressure measurements obtained within 24 hours, 3 days, and 7 days post-treatment. (4) Use of antihypertensive agents: The need for antihypertensive medications within 24 hours, 3 days, and 7 days post-treatment will be recorded. Intravenous and oral/enteral medications will be documented separately, including the number of agents used if applicable. | 24 hours, 3 days, and 7 days post-treatment |
| Glycemic Control | (1) Mean blood glucose values: The average glucose values within 24 hours, 3 days, and 7 days post-treatment will be calculated for each group using all available measurements. (2) Hypoglycemia rate: Hypoglycemia is defined as a blood glucose level <2.8 mmol/L in non-diabetic patients and <4.0 mmol/L in diabetic patients. The actual glucose value at the time of hypoglycemia will also be recorded. (3) Insulin use: The need for insulin and the total insulin dosage within 24 hours, 3 days, and 7 days post-treatment will be documented. | 24 hours, 3 days, and 7 days post-treatment |
| National Institutes of Health Stroke Scale | National Institutes of Health Stroke Scale at 7 days will be evaluated. | 7 days |
| Glasgow Coma Scale | Glasgow Coma Scale at 7 days will be evaluated. | 7 days |
| Hematoma Expansion | Hematoma expansion is defined as an absolute increase in hematoma volume ≥12.5 mL or a relative increase >33% from baseline (V₁) to 24-hour of 7 days follow-up computed tomography (V₂), where V₁ is the baseline hematoma volume and V₂ is the volume at 24 hours and 7 days. | 24 hours and 7 days |
| Quality of Life Assessment | The EuroQol Five-Dimension Three-Level Questionnaire56 will be used to assess health-related quality of life at 90 days. The EuroQol 5-dimension 3-level (EQ-5D-3L) patient-reported questionnaire covers 5 domains of health-related quality of life: mobility, selfcare, usual activities, pain and discomfort, and anxiety and depression. Each domain has 3 graded levels of response: no problems, moderate, problems, or extreme problems. Scores from these levels are combined to provide an overall health utility score that was calculated according to population norms in China. A score of 1 represents perfect health, a score of 0 represents death, and negative scores represent health states considered to be worse than death. | 90 days |
| Duration of Mechanical Ventilation | For patients requiring mechanical ventilation, the start and end times of ventilation in the intensive care unit will be recorded, and the duration will be calculated in hours. | 7 days |
| Intensive care unit Length of Stay | The dates of intensive care unit admission and discharge will be recorded, and the length of stay will be calculated in days. | 7 days |
| Hospitalization Status at 90 Days | Whether the patient remains hospitalized at 90 days will be documented. | 90 days |
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| 18551022 | Background | Zhang Y, Reilly KH, Tong W, Xu T, Chen J, Bazzano LA, Qiao D, Ju Z, Chen CS, He J. Blood pressure and clinical outcome among patients with acute stroke in Inner Mongolia, China. J Hypertens. 2008 Jul;26(7):1446-52. doi: 10.1097/HJH.0b013e328300a24a. |
| 31081862 | Background | Leasure AC, Qureshi AI, Murthy SB, Kamel H, Goldstein JN, Woo D, Ziai WC, Hanley DF, Al-Shahi Salman R, Matouk CC, Sansing LH, Sheth KN, Falcone GJ. Association of Intensive Blood Pressure Reduction With Risk of Hematoma Expansion in Patients With Deep Intracerebral Hemorrhage. JAMA Neurol. 2019 Aug 1;76(8):949-955. doi: 10.1001/jamaneurol.2019.1141. |
| 35579034 | Background | Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, Hemphill JC 3rd, Johnson R, Keigher KM, Mack WJ, Mocco J, Newton EJ, Ruff IM, Sansing LH, Schulman S, Selim MH, Sheth KN, Sprigg N, Sunnerhagen KS; American Heart Association/American Stroke Association. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022 Jul;53(7):e282-e361. doi: 10.1161/STR.0000000000000407. Epub 2022 May 17. No abstract available. |
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| 40401775 | Background | Steiner T, Purrucker JC, Aguiar de Sousa D, Apostolaki-Hansson T, Beck J, Christensen H, Cordonnier C, Downer MB, Eilertsen H, Gartly R, Gerner ST, Ho L, Holt Jahr S, Klijn CJ, Martinez-Majander N, Orav K, Petersson J, Raabe A, Sandset EC, Schreuder FH, Seiffge D, Al-Shahi Salman R. European Stroke Organisation (ESO) and European Association of Neurosurgical Societies (EANS) guideline on stroke due to spontaneous intracerebral haemorrhage. Eur Stroke J. 2025 Dec;10(4):1007-1086. doi: 10.1177/23969873251340815. Epub 2025 May 22. |
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| 36300975 | Background | Sheth KN. Spontaneous Intracerebral Hemorrhage. N Engl J Med. 2022 Oct 27;387(17):1589-1596. doi: 10.1056/NEJMra2201449. No abstract available. |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006470 | Hemorrhage |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D007093 | Imidazoles |
| D001393 | Azoles |