Early Systolic Blood Pressure Control RateASSICHHNCT03207100
Analgesia-first Minimal Sedation for Spontaneous Intracerebral Hemorrhage Early Antihypertensive Treatment
A study testing Analgesia-first minimal sedation and Antihypertensive treatment in people with Early Systolic Blood Pressure Control Rate and Hematoma Growth, run by Hong Yang at 17 sites in China.
Trial summary
This study evaluates safety and efficacy of analgesia-first minimal sedation as an early antihypertensive treatment for spontaneous intracerebral hemorrhage. The analgesia-first minimal sedation strategy relies on the remifentanil-mediated alleviation of pain-induced stress response and the antisympathetic activity of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early Systolic Blood Pressure Control Rate, Hematoma Growth, Blood Pressure Variability
- What is being tested?
- Analgesia-first minimal sedation and Antihypertensive treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 338 participants
- Where
- 17 sitesChina
- Study dates
- 6 Dec 2017to 15 May 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
- Definitive diagnosis of ICH-induced acute brain injury by CT;
- Systolic BP ≥150 mmHg for at least twice;
- >18 years old;
- Feasible for emergency antihypertensive treatment and real-time BP monitoring;
- Disease onset is within 24h;
- ICU or stroke unit admission within 24h.
Who cannot join
- Subject has contraindications for emergency intensified antihypertensive treatment;
- Intracranial hemorrhage secondary to intracranial tumor, recent trauma, cerebral infarction and thrombolytic therapy;
- History of ischemic stroke within 30 days before disease onset;
- Clinical or imaging examination reveals an expected high mortality in subject within the next 24h;
- Presence of dementia or significant post-stroke disability;
- Coagulation disorder caused by drugs or hematologic diseases;
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- Allergy to opioids;
- Interference test result, assessment and follow-up of comorbidity;
- Presence of sinus arrest, borderline rhythm, grade II and above atrioventricular block and malignant arrhythmia;
- Individual is pregnant or lactating;
- Currently participating in other drug studies or clinical trials;
- Subject or guardian is unwilling to provide his/her informed consent form, or subject is highly unable to persist with the study and follow-up;
- Subject's participation in the study will increase his/her study-related risk, and other reasons that make the subject unsuitable for the study as determined by the investigator.
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
China17 sites
Xuanwu Hospital Capital Medical University
Beijing, Beijing Municipality, 100053
Xinqiao Hospital of Army Medical University
Chongqing, Chongqing Municipality, 400037
Guangdong 999 Brain Hospital
Guangzhou, Guangdong, 510000
The Third Affiliated Hospital of Southern Medical University
Guangzhou, Guangdong, 510630
The Fifth Affiliated Hospital of Southern Medical University
Guangzhou, Guangdong, 510900
The Second Hospital University of South China
Hengyang, Hunan, 421001
The First Affiliated Hospital of HuNan University of Medicine
Huaihua, Hunan, 418000
The First Affiliated Hospital of Kuming Medical University
Kunming, Yunnan, 650032
The First Hospital of Lanzhou University
Lanzhou, Gansu, 730000
MaoMing People's Hospital
Maoming, Guangdong, 525000
The People's Hospital of Guangxi Zhuang Autonomous Region
Nanning, Guangxi, 530021
Qilu Hospital of Shandong University
Qingdao, Shandong, 266035
The Second People's Hospital of Shenzhen
Shenzhen, Guangdong, 518035
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang, 830054
Henan Provincial People's Hospital
Zhengzhou, Henan, 450003
Zhongshan People's Hospital
Zhongshan, Guangdong, 528400
The Fifth Affiliated Hospital Sun-yet sen University
Zhuhai, Guangdong, 519000
About this study
Official title: Clinical Study of the Safety and Efficacy of Analgesia-first Minimal Sedation as an Early Antihypertensive Treatment for Spontaneous Intracerebral Hemorrhage
This study evaluates safety and efficacy of analgesia-first minimal sedation as an early antihypertensive treatment for spontaneous intracerebral hemorrhage. The analgesia-first minimal sedation strategy relies on the remifentanil-mediated alleviation of pain-induced stress response and the antisympathetic activity of dexmedetomidine to restore the elevated blood pressure to normal level in patients with spontaneous intracerebral hemorrhage. This strategy allows rapid stabilization of blood pressure, and its use as a pre-treatment for patients on mechanical ventilation prior to painful procedures reduces blood pressure variability and thereby results in etiologic treatment. It is more effective in blood pressure control than conventional symptomatic antihypertensive treatment, reduces the incidence of early hematoma expansion and improves prognosis, ,lowers healthcare workers workload, increases patient adherence, and improves healthcare worker satisfaction.
Read the detailed description
Spontaneous intracerebral hemorrhage (ICH) is hemorrhage in the brain parenchyma caused by non-traumatic spontaneous rupture of cerebral artery, arteriole, vein and capillary in adults. ICH is a common problem, with subarachnoid hemorrhage. About 90% ICH patients have increased blood pressure (BP) that usually occurs immediately after disease onset. BP elevation in the acute phase of ICH is associated with poor prognosis, and its mechanism of action includes the local increase of initial hemorrhage, early hematoma expansion at hemorrhagic sites, the increased risk of early recurrent hemorrhage, serious cerebral edema, and recurrent stroke, this affects the most within the few hours following the onset of the disease. The current American Heart Association guidelines recommended early antihypertensive treatment and suggested that rapid decrease of BP to 140 mmHg is safe in ICH patients with no obvious antihypertensive contraindications. However, the significant differences between large studies conducted in recent years have led to great controversy on the effect of early antihypertensive treatment in acute ICH and disease prognosis. A meta-analysis of early antihypertensive treatment for ICH showed that differences in early BP control rate and BP increase variability are also the major causes of inconsistency between these studies. There is currently no consensus on the best antihypertensive regimen as it is difficult to reach the optimal BP level timely. Some studies have shown that stress response, pain, ICP increase and pre-onset BP elevation are factors that cause acute BP increase in ICH patients. In particular, restlessness, sleep deprivation, and stress due to intolerable pain can lead to dramatic BP and intracranial pressure (ICP) increases, further lead to secondary intracerebral hematoma expansion and subsequently cause neurologic degeneration and cerebral tissue damage. Therefore, the primary principles of ICH acute BP increase treatment are to keep quiet, restore BP to normal level, stably reduce BP, decrease BP variability, lower the chance of recurrent hemorrhage, and thereby improve long-term prognosis. Traditional antihypertensive treatment can only resolve the issue of BP elevation but not the root cause of disease. Analgesia and sedation is a critical component of and a global consensus in the clinical management of ICH patients. Remifentanil is a fentanyl μ-type opioid receptor agonist with strong and fast-acting analgesic effects, does not induce ICP elevation and can alleviate pain induced by sputum aspiration, body turning and back clapping in severe patients. A randomized trial on patients with craniocerebral injury has indicated that a remifentanil-based sedation strategy can significantly reduce the amount of sedative used and shorten the time of mechanical ventilation without affecting the functional assessment of the nervous system. Dexmedetomidine is an α2-adrenergic agonist that inhibits sympathetic activity by activating the pre-synaptic α2-receptor in the locus coeruleus, which in turn reduces norepinephrine release, that only slightly affects consciousness and breathing and helps patients with craniocerebral injury stay conscious while under sedation, allowing real-time functional assessment of the nervous system. Therefore, the research group developed a treatment strategy in which sufficient analgesia is applied in combination with a minimal sedation program as an effective and safe early an- tihypertensive treatment.We hypothesize that applying sufficient analgesia in combination with a minimal sedation program will involve the use of remifentanil for pain relief and dexmedetomidine for antisympathetic activity to restore elevated BP to normal levels in patients with spontaneous ICH, and we further hypothesize that this strategy will be more effective than conventional symptomatic antihypertensive treatment for controlling BP.
- Conditions
- Early Systolic Blood Pressure Control Rate, Hematoma Growth, Blood Pressure Variability, Healthcare Worker Satisfaction, Duration of ICU Treatment and Mechanical Ventilation
- Being tested
- Analgesia-first minimal sedation, Antihypertensive treatment
- Keywords
- Intracerebral hemorrhage, Early antihypertensive treatment, Analgesia-first, Sedation
- Medical subject headings
- Cerebral Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Analgesia-first minimal sedationCombination product
Remifentanil will be administered by IV infusion and maintained at a dose of 0.025 μg/kg/min in non-mechanically ventilated patients and a dose of 0.05 μg/kg/min in mechanically ventilated patients. BP will be measured after 10 min of continuous infusion.If systolic BP is still ≥ 140 mmHg, then dexmedetomidine will be applied using an infusion pump at a dose of 0.2 μg/kg/h. BP will be measured again after 15 min of continuous infusion of dexmedetomidine. If systolic BP is still ≥ 140 mmHg, the dose of dexmedetomidine can be increased 0.1 μg/kg/h to the maximum of 0.6 μg/kg/h.If the maximum dose of dexmedetomidine does not lower blood pressure, use routine blood pressure reduction programs in each center to reduce blood pressure to the target range. Mechanically ventilated patients will be given a rapid remifentanil (0.5 μg/kg) infusion to reduce procedure-related pain.
Antihypertensive treatmentCombination product
Routine antihypertensive treatment will be performed in accordance with the protocol of each respective research center. Urapidil, nicardipine, and labetalol will be used in this group. Urapidil will be used as follows: a slow IV injection of 10-15 mg and then IV pumping for maintenance at an initial rate of 2 mg/min, adjusted according to BP to a maximum of 9 mg/min. Nicardipine will be used as follows: IV pumping at 0.5μg/kg/min adjusted according to BP to a maximum of 6μg/kg/min. Labetalol will be used as follows: IV infusion for maintenance at 1-4 mg/min until the aim is reached.The mechanically ventilated patients in the control group will be administered a rapid physiological saline infusion as a controlled pretreatment.
| Study group | Role | What they receive |
|---|---|---|
| Analgesia-first minimal sedation group | Experimental | Using analgesia-first minimal sedation strategy to implement antihypertensive therapy. Receives: Combination Product: Analgesia-first minimal sedation |
| Antihypertensive drug treatment group | Active comparator | Using routine antihypertensive drugs to implement antihypertensive therapy. Receives: Combination Product: Antihypertensive treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic BP control rate at 1h post-treatment initiation
The number of patients who systolic BP decreased to <140 mmHg at 1h post-treatment initiation compared to the total number of each group.
Measured: 1h post-treatment initiation
Secondary outcomes (8)
Hematoma growth at 24 h
Head CT re-examination is required for the subjects after 24h of treatment.Hematoma expansion is defined as V2-V1≥12.5 cm³ or (V2-V1)/V1>33% (V1 and V2 represent the hematoma volume in the two CT scans, respectively).
Measured: 24h of treatment
BP variability
BPs are also recorded every hour from hour 2 to 24 post-treatment, and monitored on d2-d7 of treatment of recorded every 6h daily (4 times per day); BP Coefficient of Variation (CV) = (standard deviation of BP/mean of systolic BP).
Measured: Up to 7 days
Neurologic function
Assessed once every morning using the National Institutes of Health Stroke Scale (NIHSS), Glasgow Coma Scale scores (GCS), Richmond Agitation-Sedation Scale (RASS), Nonverbal Adult Pain Assessment Scale (NVPS), Reaction Level Scale (RLS).
Measured: Up to 7 days
Duration of ICU treatment and mechanical ventilation
Duration of ICU treatment and mechanical ventilation
Measured: Up to 7 days
Healthcare worker satisfaction
Questionnaire is designed based on the Copenhagen Psychosocial Questionnaire, with a parameter for self-assessed workload.
Measured: 7 day or discharge from ICU (if patients discharge from ICU in 7 days)
cerebral tissue oxygenation index (TOI)
Assess changes in the TOI after sputum aspiration in mechanical ventilation patients
Measured: Up to 7 days and around sputum aspiration
28-day mortality and disability rate
Using a binary indicator of the patient's death or dependency at 28 days, with dependency being defined by a score of 3 to 5 on the modified Rankin Score (mRS)
Measured: 28 days
90-day mortality and disability rate
Using a binary indicator of the patient's death or dependency at 90 days, with dependency being defined by a score of 3 to 5 on the modified Rankin Score (mRS)
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 posted2 Jul 2017
- Study start6 Dec 2017
- Primary completion14 Feb 2021
- Study completion15 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (43)Papers the sponsor has linked to this study.
- Other trials for Early Systolic Blood Pressure Control RateStudies 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
- Model description
- Subjects are grouped into the analgesia-first minimal sedation group (experimental group) or antihypertensive drug treatment group (control group) using the central randomization system upon enrollment. Antihypertensive intervention is performed on the subjects in accordance to the protocol of each group.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 338 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hong Yang
- Sponsor type
- Other government
- Collaborators
- Xuanwu Hospital, Beijing, Qilu Hospital of Shandong University, First Affiliated Hospital of Kunming Medical University, First Affiliated Hospital of Xinjiang Medical University, Second Affiliated Hospital of Third Military Medical University, Henan Provincial People's Hospital, The Second Hospital University of South China, Shenzhen Second People's Hospital, People's Hospital of Guangxi Zhuang Autonomous Region, Department of Biostatistics, Southern Medical University, LanZhou University, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Guangdong 999 Brain Hospital, Maoming People's Hospital, The Fifth Affiliated Hospital of Southern Medical University, Zhongshan People's Hospital, Guangdong, China, Fifth Affiliated Hospital, Sun Yat-Sen University
- Responsible party
- Sponsor-investigator, Hong Yang, The Third Affiliated Hospital of Southern Medical University
- Investigators
- Wen-Jin Chen, Study chair, Xuanwu Hospital, BeijingHong Yang, Dr, Study chair, The Third Affiliated Hospital of Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03207100
- Sponsor's protocol ID
- 201704004
- Acronym
- ASSICHH
- Status last verified
- Dec 2023
- First submitted
- 26 Jun 2017
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001 May 10;344(19):1450-60. doi: 10.1056/NEJM200105103441907. No abstract available.
PubMed 11346811Chen ST, Chen SD, Hsu CY, Hogan EL. Progression of hypertensive intracerebral hemorrhage. Neurology. 1989 Nov;39(11):1509-14. doi: 10.1212/wnl.39.11.1509.
PubMed 2812332Broderick JP, Brott TG, Tomsick T, Barsan W, Spilker J. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg. 1990 Feb;72(2):195-9. doi: 10.3171/jns.1990.72.2.0195.
PubMed 2295917Arakawa S, Saku Y, Ibayashi S, Nagao T, Fujishima M. Blood pressure control and recurrence of hypertensive brain hemorrhage. Stroke. 1998 Sep;29(9):1806-9. doi: 10.1161/01.str.29.9.1806.
PubMed 9731599van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement for the assessment of handicap in stroke patients. Stroke. 1988 May;19(5):604-7. doi: 10.1161/01.str.19.5.604.
PubMed 3363593Koskinen LO, Olivecrona M, Grande PO. Severe traumatic brain injury management and clinical outcome using the Lund concept. Neuroscience. 2014 Dec 26;283:245-55. doi: 10.1016/j.neuroscience.2014.06.039. Epub 2014 Jun 25.
PubMed 24973658Stocchetti N, Pagan F, Calappi E, Canavesi K, Beretta L, Citerio G, Cormio M, Colombo A. Inaccurate early assessment of neurological severity in head injury. J Neurotrauma. 2004 Sep;21(9):1131-40. doi: 10.1089/neu.2004.21.1131.
PubMed 15453984Oddo M, Crippa IA, Mehta S, Menon D, Payen JF, Taccone FS, Citerio G. Optimizing sedation in patients with acute brain injury. Crit Care. 2016 May 5;20(1):128. doi: 10.1186/s13054-016-1294-5.
PubMed 27145814Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G. Volume of intracerebral hemorrhage. A powerful and easy-to-use predictor of 30-day mortality. Stroke. 1993 Jul;24(7):987-93. doi: 10.1161/01.str.24.7.987.
PubMed 8322400Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke. 1996 Oct;27(10):1783-7. doi: 10.1161/01.str.27.10.1783.
PubMed 8841330Kasner SE. Clinical interpretation and use of stroke scales. Lancet Neurol. 2006 Jul;5(7):603-12. doi: 10.1016/S1474-4422(06)70495-1.
PubMed 16781990Teasdale 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 25030516Barr J, Fraser GL, Puntillo K, Ely EW, Gelinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R; American College of Critical Care Medicine. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the Intensive Care Unit: executive summary. Am J Health Syst Pharm. 2013 Jan 1;70(1):53-8. doi: 10.1093/ajhp/70.1.53.
PubMed 23261901Stalhammar D, Starmark JE, Holmgren E, Eriksson N, Nordstrom CH, Fedders O, Rosander B. Assessment of responsiveness in acute cerebral disorders. A multicentre study on the reaction level scale (RLS 85). Acta Neurochir (Wien). 1988;90(3-4):73-80. doi: 10.1007/BF01560558.
PubMed 3354366Pejtersen JH, Kristensen TS, Borg V, Bjorner JB. The second version of the Copenhagen Psychosocial Questionnaire. Scand J Public Health. 2010 Feb;38(3 Suppl):8-24. doi: 10.1177/1403494809349858.
PubMed 21172767
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Study of the Safety and Efficacy of Analgesia-first Minimal Sedation as an Early Antihypertensive Treatment for Spontaneous Intracerebral Hemorrhage
- ClinicalTrials.gov ID
- NCT03207100
- Acronym / sponsor ID
- ASSICHH / 201704004
- Conditions
- Early Systolic Blood Pressure Control Rate, Hematoma Growth, Blood Pressure Variability, Healthcare Worker Satisfaction, Duration of ICU Treatment and Mechanical Ventilation
- Keywords
- Intracerebral hemorrhage, Early antihypertensive treatment, Analgesia-first, Sedation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 338 participants (actual)
- Lead sponsor
- Hong YangOther government
- Collaborators
- Xuanwu Hospital, Beijing, Qilu Hospital of Shandong University, First Affiliated Hospital of Kunming Medical University, First Affiliated Hospital of Xinjiang Medical University, Second Affiliated Hospital of Third Military Medical University, Henan Provincial People's Hospital, The Second Hospital University of South China, Shenzhen Second People's Hospital, People's Hospital of Guangxi Zhuang Autonomous Region, Department of Biostatistics, Southern Medical University, LanZhou University, The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Guangdong 999 Brain Hospital, Maoming People's Hospital, The Fifth Affiliated Hospital of Southern Medical University, Zhongshan People's Hospital, Guangdong, China, Fifth Affiliated Hospital, Sun Yat-Sen University
- Study start
- 6 Dec 2017 (actual)
- Primary completion
- 14 Feb 2021 (actual)
- Study completion
- 15 May 2021 (actual)
- First posted
- 2 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates safety and efficacy of analgesia-first minimal sedation as an early antihypertensive treatment for spontaneous intracerebral hemorrhage. The analgesia-first minimal sedation strategy relies on the remifentanil-mediated alleviation of pain-induced stress response and the antisympathetic activity of dexmedetomidine to restore the elevated blood pressure to normal level in patients with spontaneous intracerebral hemorrhage. This strategy allows rapid stabilization of blood pressure, and its use as a pre-treatment for patients on mechanical ventilation prior to painful procedures reduces blood pressure variability and thereby results in etiologic treatment. It is more effective in blood pressure control than conventional symptomatic antihypertensive treatment, reduces the incidence of early hematoma expansion and improves prognosis, ,lowers healthcare workers workload, increases patient adherence, and improves healthcare worker satisfaction.
Detailed description
Spontaneous intracerebral hemorrhage (ICH) is hemorrhage in the brain parenchyma caused by non-traumatic spontaneous rupture of cerebral artery, arteriole, vein and capillary in adults. ICH is a common problem, with subarachnoid hemorrhage. About 90% ICH patients have increased blood pressure (BP) that usually occurs immediately after disease onset. BP elevation in the acute phase of ICH is associated with poor prognosis, and its mechanism of action includes the local increase of initial hemorrhage, early hematoma expansion at hemorrhagic sites, the increased risk of early recurrent hemorrhage, serious cerebral edema, and recurrent stroke, this affects the most within the few hours following the onset of the disease. The current American Heart Association guidelines recommended early antihypertensive treatment and suggested that rapid decrease of BP to 140 mmHg is safe in ICH patients with no obvious antihypertensive contraindications. However, the significant differences between large studies conducted in recent years have led to great controversy on the effect of early antihypertensive treatment in acute ICH and disease prognosis. A meta-analysis of early antihypertensive treatment for ICH showed that differences in early BP control rate and BP increase variability are also the major causes of inconsistency between these studies. There is currently no consensus on the best antihypertensive regimen as it is difficult to reach the optimal BP level timely. Some studies have shown that stress response, pain, ICP increase and pre-onset BP elevation are factors that cause acute BP increase in ICH patients. In particular, restlessness, sleep deprivation, and stress due to intolerable pain can lead to dramatic BP and intracranial pressure (ICP) increases, further lead to secondary intracerebral hematoma expansion and subsequently cause neurologic degeneration and cerebral tissue damage. Therefore, the primary principles of ICH acute BP increase treatment are to keep quiet, restore BP to normal level, stably reduce BP, decrease BP variability, lower the chance of recurrent hemorrhage, and thereby improve long-term prognosis. Traditional antihypertensive treatment can only resolve the issue of BP elevation but not the root cause of disease. Analgesia and sedation is a critical component of and a global consensus in the clinical management of ICH patients. Remifentanil is a fentanyl μ-type opioid receptor agonist with strong and fast-acting analgesic effects, does not induce ICP elevation and can alleviate pain induced by sputum aspiration, body turning and back clapping in severe patients. A randomized trial on patients with craniocerebral injury has indicated that a remifentanil-based sedation strategy can significantly reduce the amount of sedative used and shorten the time of mechanical ventilation without affecting the functional assessment of the nervous system. Dexmedetomidine is an α2-adrenergic agonist that inhibits sympathetic activity by activating the pre-synaptic α2-receptor in the locus coeruleus, which in turn reduces norepinephrine release, that only slightly affects consciousness and breathing and helps patients with craniocerebral injury stay conscious while under sedation, allowing real-time functional assessment of the nervous system. Therefore, the research group developed a treatment strategy in which sufficient analgesia is applied in combination with a minimal sedation program as an effective and safe early an- tihypertensive treatment.We hypothesize that applying sufficient analgesia in combination with a minimal sedation program will involve the use of remifentanil for pain relief and dexmedetomidine for antisympathetic activity to restore elevated BP to normal levels in patients with spontaneous ICH, and we further hypothesize that this strategy will be more effective than conventional symptomatic antihypertensive treatment for controlling BP.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Subjects are grouped into the analgesia-first minimal sedation group (experimental group) or antihypertensive drug treatment group (control group) using the central randomization system upon enrollment. Antihypertensive intervention is performed on the subjects in accordance to the protocol of each group.
| Arm | Type | Receives |
|---|---|---|
| Analgesia-first minimal sedation group | Experimental | Combination Product: Analgesia-first minimal sedationUsing analgesia-first minimal sedation strategy to implement antihypertensive therapy. |
| Antihypertensive drug treatment group | Active comparator | Combination Product: Antihypertensive treatmentUsing routine antihypertensive drugs to implement antihypertensive therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Definitive diagnosis of ICH-induced acute brain injury by CT;
- Systolic BP ≥150 mmHg for at least twice;
- >18 years old;
- Feasible for emergency antihypertensive treatment and real-time BP monitoring;
- Disease onset is within 24h;
Key exclusion criteria (13 listed)
- Subject has contraindications for emergency intensified antihypertensive treatment;
- Intracranial hemorrhage secondary to intracranial tumor, recent trauma, cerebral infarction and thrombolytic therapy;
- History of ischemic stroke within 30 days before disease onset;
- Clinical or imaging examination reveals an expected high mortality in subject within the next 24h;
- Presence of dementia or significant post-stroke disability;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Analgesia-first minimal sedationRemifentanil will be administered by IV infusion and maintained at a dose of 0.025 μg/kg/min in non-mechanically ventilated patients and a dose of 0.05 μg/kg/min in mechanically ventilated patients. BP will be measured after 10 min of continuous infusion.If systolic BP is still ≥ 140 mmHg, then dexmedetomidine will be applied using an infusion pump at a dose of 0.2 μg/kg/h. BP will be measured again after 15 min of continuous infusion of dexmedetomidine. If systolic BP is still ≥ 140 mmHg, the dose of dexmedetomidine can be increased 0.1 μg/kg/h to the maximum of 0.6 μg/kg/h.If the maximum dose of dexmedetomidine does not lower blood pressure, use routine blood pressure reduction programs in each center to reduce blood pressure to the target range. Mechanically ventilated patients will be given a rapid remifentanil (0.5 μg/kg) infusion to reduce procedure-related pain. | Combination product | Analgesia-first minimal sedation group |
| Antihypertensive treatmentRoutine antihypertensive treatment will be performed in accordance with the protocol of each respective research center. Urapidil, nicardipine, and labetalol will be used in this group. Urapidil will be used as follows: a slow IV injection of 10-15 mg and then IV pumping for maintenance at an initial rate of 2 mg/min, adjusted according to BP to a maximum of 9 mg/min. Nicardipine will be used as follows: IV pumping at 0.5μg/kg/min adjusted according to BP to a maximum of 6μg/kg/min. Labetalol will be used as follows: IV infusion for maintenance at 1-4 mg/min until the aim is reached.The mechanically ventilated patients in the control group will be administered a rapid physiological saline infusion as a controlled pretreatment. | Combination product | Antihypertensive drug treatment group |
Primary outcome
Systolic BP control rate at 1h post-treatment initiation
Time frame: 1h post-treatment initiation
The number of patients who systolic BP decreased to <140 mmHg at 1h post-treatment initiation compared to the total number of each group.
8 secondary outcomes
Hematoma growth at 24 h
Time frame: 24h of treatment
BP variability
Time frame: Up to 7 days
Neurologic function
Time frame: Up to 7 days
Duration of ICU treatment and mechanical ventilation
Time frame: Up to 7 days
Healthcare worker satisfaction
Time frame: 7 day or discharge from ICU (if patients discharge from ICU in 7 days)
cerebral tissue oxygenation index (TOI)
Time frame: Up to 7 days and around sputum aspiration
28-day mortality and disability rate
Time frame: 28 days
90-day mortality and disability rate
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Background: PubMed 11346811Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous intracerebral hemorrhage. N Engl J Med. 2001 May 10;344(19):1450-60. doi: 10.1056/NEJM200105103441907. No abstract available.
- Background: PubMed 2812332Chen ST, Chen SD, Hsu CY, Hogan EL. Progression of hypertensive intracerebral hemorrhage. Neurology. 1989 Nov;39(11):1509-14. doi: 10.1212/wnl.39.11.1509.
- Background: PubMed 2295917Broderick JP, Brott TG, Tomsick T, Barsan W, Spilker J. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg. 1990 Feb;72(2):195-9. doi: 10.3171/jns.1990.72.2.0195.
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- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wen-Jin Chen study chair
Xuanwu Hospital, Beijing
Hong Yang, Dr study chair
The Third Affiliated Hospital of Southern Medical University
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Analgesia-first minimal sedation and Antihypertensive treatment in people with Early Systolic Blood Pressure Control Rate and Hematoma Growth, run by Hong Yang at 17 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Systolic BP control rate at 1h post-treatment initiation (time frame: 1h post-treatment initiation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03207100, which also lists 43 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2023.