Analgesia-first Minimal Sedation for Spontaneous Intracerebral Hemorrhage Early Antihypertensive Treatment (ASSICHH)

December 5, 2023 updated by: Hong Yang

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
338

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100053
        • Xuanwu Hospital Capital Medical University
    • Chongqing
      • Chongqing, Chongqing, China, 400037
        • Xinqiao Hospital of Army Medical University
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • The First Hospital of Lanzhou University
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Guangdong 999 Brain Hospital
      • Guangzhou, Guangdong, China, 510630
        • The Third Affiliated Hospital of Southern Medical University
      • Guangzhou, Guangdong, China, 510900
        • The Fifth Affiliated Hospital of Southern Medical University
      • Maoming, Guangdong, China, 525000
        • Maoming People's Hospital
      • Shenzhen, Guangdong, China, 518035
        • The Second People's Hospital of Shenzhen
      • Zhongshan, Guangdong, China, 528400
        • Zhongshan People's Hospital
      • Zhuhai, Guangdong, China, 519000
        • The Fifth Affiliated Hospital Sun-yet sen University
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • The People's Hospital of Guangxi Zhuang Autonomous Region
    • Henan
      • Zhengzhou, Henan, China, 450003
        • Henan Provincial People's Hospital
    • Hunan
      • Hengyang, Hunan, China, 421001
        • The Second Hospital University of South China
      • Huaihua, Hunan, China, 418000
        • The First Affiliated Hospital of Hunan University of Medicine
    • Shandong
      • Qingdao, Shandong, China, 266035
        • Qilu Hospital of Shandong University
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830054
        • The First Affiliated Hospital of Xinjiang Medical University
    • Yunnan
      • Kunming, Yunnan, China, 650032
        • The First Affiliated Hospital of Kuming Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Definitive diagnosis of ICH-induced acute brain injury by CT;
  2. Systolic BP ≥150 mmHg for at least twice;
  3. >18 years old;
  4. Feasible for emergency antihypertensive treatment and real-time BP monitoring;
  5. Disease onset is within 24h;
  6. ICU or stroke unit admission within 24h.

Exclusion Criteria:

  1. Subject has contraindications for emergency intensified antihypertensive treatment;
  2. Intracranial hemorrhage secondary to intracranial tumor, recent trauma, cerebral infarction and thrombolytic therapy;
  3. History of ischemic stroke within 30 days before disease onset;
  4. Clinical or imaging examination reveals an expected high mortality in subject within the next 24h;
  5. Presence of dementia or significant post-stroke disability;
  6. Coagulation disorder caused by drugs or hematologic diseases;
  7. Allergy to opioids;
  8. Interference test result, assessment and follow-up of comorbidity;
  9. Presence of sinus arrest, borderline rhythm, grade II and above atrioventricular block and malignant arrhythmia;
  10. Individual is pregnant or lactating;
  11. Currently participating in other drug studies or clinical trials;
  12. 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;
  13. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Analgesia-first minimal sedation group
Using analgesia-first minimal sedation strategy to implement antihypertensive therapy.
Combination product: Analgesia-first minimal sedation
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.
Active Comparator: Antihypertensive drug treatment group
Using routine antihypertensive drugs to implement antihypertensive therapy.
Combination product: Antihypertensive treatment
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
1h post-treatment initiation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hematoma growth at 24 h
Time Frame: 24h of treatment
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).
24h of treatment
BP variability
Time Frame: Up to 7 days
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).
Up to 7 days
Neurologic function
Time Frame: Up to 7 days
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).
Up to 7 days
Duration of ICU treatment and mechanical ventilation
Time Frame: Up to 7 days
Duration of ICU treatment and mechanical ventilation
Up to 7 days
Healthcare worker satisfaction
Time Frame: 7 day or discharge from ICU (if patients discharge from ICU in 7 days)
Questionnaire is designed based on the Copenhagen Psychosocial Questionnaire, with a parameter for self-assessed workload.
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
Assess changes in the TOI after sputum aspiration in mechanical ventilation patients
Up to 7 days and around sputum aspiration
28-day mortality and disability rate
Time Frame: 28 days
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)
28 days
90-day mortality and disability rate
Time Frame: 90 days
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)
90 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hong Yang

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
LanZhou University
Qilu Hospital of Shandong University
Xuanwu Hospital, Beijing
Henan Provincial People's Hospital
Fifth Affiliated Hospital, Sun Yat-Sen University
Shenzhen Second People's Hospital
First Affiliated Hospital of Xinjiang Medical University
The Fifth Affiliated Hospital of Southern Medical University
Zhongshan People's Hospital, Guangdong, China
People's Hospital of Guangxi
Guangdong 999 Brain Hospital
Maoming People's Hospital
The Second Hospital University of South China
Second Affiliated Hospital of Third Military Medical University
First Affiliated Hospital of Kunming Medical University
Department of Biostatistics, Southern Medical University
The First Affiliated Hospital of HuNan University of Medicine

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Wen-Jin Chen, Xuanwu Hospital, Beijing
  • Study Chair: Hong Yang, Dr, The Third Affiliated Hospital of Southern Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 6, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 14, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 15, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 26, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2017

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 7, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 5, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 201704004

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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