Intracerebral HemorrhageREADY-ICHNCT07695220
REmifentanil And Dexmedetomidine for EarlY Intensive Blood Pressure Lowering in ICH.
A study testing Remifentanil and Dexmedetomidine in people with Intracerebral Hemorrhage, run by The Third Affiliated Hospital of Southern Medical University.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracerebral Hemorrhage
- What is being tested?
- Remifentanil and Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,116 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2026to 31 Dec 2028
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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.
Read the 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.
- Conditions
- Intracerebral Hemorrhage
- Being tested
- Remifentanil and Dexmedetomidine, Guideline standard care
- Keywords
- Intracerebral hemorrhage, Remifentanil, Dexmedetomidine, Blood pressure-lowering
- Medical subject headings
- Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Remifentanil and DexmedetomidineDrug
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.
Guideline standard careDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Remifentanil and Dexmedetomidine |
| 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". Receives: Drug: Guideline standard care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days post-treatment
Secondary outcomes (10)
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.
Measured: 90 days post-treatment
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.
Measured: 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.
Measured: 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. National Institute of Health Stroke Scale, range from 0 to 42, with higher scores indicating more severe neurological deficits.
Measured: 7 days
Glasgow Coma Scale
Glasgow Coma Scale at 7 days will be evaluated. Glasgow Coma Scale ranges from 3 to 15; 15 is considered fully conscious, and 3 is considered deep coma.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7 days
Hospitalization Status at 90 Days
Whether the patient remains hospitalized at 90 days will be documented.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Oct 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (61)Papers the sponsor has linked to this study.
- Other trials for Intracerebral HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Third Affiliated Hospital of Southern Medical University
- Sponsor type
- Other government
- Collaborators
- Shenzhen People's Hospital
- Responsible party
- Principal investigator, Hong Yang, The Third Affiliated Hospital of Southern Medical University
- Investigators
- Hong Yang, MD, Principal investigator, The Third Affiliated Hospital of Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07695220
- Sponsor's protocol ID
- 2026SMU017
- Acronym
- READY-ICH
- Status last verified
- Jul 2026
- First submitted
- 28 Jun 2026
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 32419182Teasdale 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.
PubMed 25030516Society 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.
PubMed 30009721Hopewell 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, Thabane L, Torgerson D, Vohra S, White IR, Boutron I. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ. 2025 Apr 14;389:e081123. doi: 10.1136/bmj-2024-081123.
PubMed 40228833Liu 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.
PubMed 25128053Rabin R, de Charro F. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001 Jul;33(5):337-43. doi: 10.3109/07853890109002087.
PubMed 11491192Brott 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.
PubMed 2749846Saver 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.
PubMed 21719772Xiong J, Quan J, Qin C, Wang X, Dong Q, Zhang B. Remifentanil pretreatment attenuates brain nerve injury in response to cardiopulmonary bypass by blocking AKT/NRF2 signal pathway. Immunopharmacol Immunotoxicol. 2022 Aug;44(4):574-585. doi: 10.1080/08923973.2022.2069577. Epub 2022 Apr 29.
PubMed 35485905Unchiti K, Leurcharusmee P, Samerchua A, Pipanmekaporn T, Chattipakorn N, Chattipakorn SC. The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies. Eur J Neurosci. 2021 Nov;54(9):7006-7047. doi: 10.1111/ejn.15474. Epub 2021 Oct 25.
PubMed 34561931Song HL, Zhang SB. Therapeutic effect of dexmedetomidine on intracerebral hemorrhage via regulating NLRP3. Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2612-2619. doi: 10.26355/eurrev_201903_17411.
PubMed 30964190Huang J, Jiang Q. Dexmedetomidine Protects Against Neurological Dysfunction in a Mouse Intracerebral Hemorrhage Model by Inhibiting Mitochondrial Dysfunction-Derived Oxidative Stress. J Stroke Cerebrovasc Dis. 2019 May;28(5):1281-1289. doi: 10.1016/j.jstrokecerebrovasdis.2019.01.016. Epub 2019 Feb 20.
PubMed 30797643Liu H, Busl KM, Dore S. Role of Dexmedetomidine in Aneurysmal Subarachnoid Hemorrhage: A Comprehensive Scoping Review. J Neurosurg Anesthesiol. 2022 Apr 1;34(2):176-182. doi: 10.1097/ANA.0000000000000728.
PubMed 33060552Tipps LB, Coplin WM, Murry KR, Rhoney DH. Safety and feasibility of continuous infusion of remifentanil in the neurosurgical intensive care unit. Neurosurgery. 2000 Mar;46(3):596-601; discussion 601-2. doi: 10.1097/00006123-200003000-00015.
PubMed 10719856Bischoff P, Plumer L, Scholz J, Drogemeier K, von Knobelsdorff G, Schulte am Esch J. [Effect of remifentanil on clinical and electroencephalographic parameters of depth of anesthesia in balanced anesthesia with propofol, enflurane or isoflurane]. Anaesthesiol Reanim. 1998;23(5):116-23. German.
PubMed 9854329