The Effect of BIA Monitoring of Brain Edema on the Neurological Prognosis of Supratentorial Massive ICH

Study Overview
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Brief Summary
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Spontaneous cerebral hemorrhage (SICH) is a hemorrhage caused by the rupture of a blood vessel within the brain parenchyma that is non-traumatic. Its rapid onset and dangerous condition seriously threaten human health; it accounts for about 15% of strokes and 50% of stroke-related mortality. Hunan Province is recognized as one of the high incidence areas of cerebral hemorrhage in the world; according to statistics, the direct economic loss caused by cerebral hemorrhage in Hunan Province is more than 1 billion yuan per year, which should be paid great attention. A 30-day follow-up study of large-volume cerebral hemorrhage (defined as supratentorial hemorrhage greater than 30 ml, infratentorial greater than 5 ml, and thalamus and cerebellum greater than 15 ml) found that the morbidity and mortality rate of ICH with hemorrhage of 30-60 ml was as high as 44-74%, while the morbidity and mortality rate of ICH with hemorrhage of <30 ml was 19% and that of >60 ml was 91%. According to studies, the occurrence of hematoma occupancy and malignant cerebral edema in large-volume cerebral hemorrhage can lead to secondary malignant intracranial pressure elevation and subsequent secondary brain injury, which are the main factors of high morbidity and mortality and poor prognosis in patients with large-volume cerebral hemorrhage. Clinical monitoring and management is the key to treatment, and despite aggressive surgical treatment and anti-brain edema therapy, a large number of patients progress to malignant brain edema disease, leading to poor outcomes. Therefore, this project intends to conduct a multicenter clinical trial of non-invasive monitoring of large volume cerebral hemorrhage on the curtain in the Hunan region to explore the impact of non-invasive brain edema monitoring management based on bioelectrical impedance technology on patient prognosis; and to explore early biomarkers of malignant brain edema through metabolomic analysis and the mechanism of malignant brain edema occurrence through multi-omic analysis to provide data support for the clinical treatment application of malignant brain edema.

Detailed Description
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Intracranial pressure and cerebral edema monitoring are commonly used neurological monitoring modalities in neurocritical conditions worldwide. There remains uncertainty in the prognosis of neurological function in patients with traumatic and non-traumatic brain injury with invasive intracranial pressure monitoring, non-invasive intracranial pressure monitoring and cerebral edema monitoring modalities, and differences in clinical practice between the two tests in patients with large volume cerebral hemorrhage. The objectives of this study were to explore the differences between non-invasive brain edema monitoring based on BIA technology (Chongqing Born-Fruk Medical Equipment Co., Ltd., Chongqing, China) and invasive intracranial pressure monitoring, and whether non-invasive brain edema monitoring based on BIA technology is more beneficial for the long-term prognosis of patients with episodic large-volume cerebral hemorrhage, whether there are fewer complications, and whether such monitoring measures are more acceptable in clinical practice. The trial is a prospective, randomized, open-label, controlled, multi-clinical center trial; the sample size was calculated based on previous studies to include a total of approximately 776 cases, and is expected to include more than 20 clinical institutions with extensive experience in the treatment of large volume cerebral hemorrhage in Hunan Province, China. Patients diagnosed with supratentorial parenchymal cerebral hemorrhage (hemorrhage volume ≥ 30 ml according to the Coniglobus formula ) by CT examination within 48 hours of onset were included, and informed consent was provided to patients who met the enrollment criteria. The included cases were divided into surgical and non-surgical groups according to the guidelines for the treatment of cerebral hemorrhage and taking into account the patient's condition, the physician's decision and the family's choice of whether to receive surgical treatment (craniotomy or minimally invasive surgery) or conservative treatment, thus avoiding the ethical risk of large-volume cerebral hemorrhage. Enrolled non-surgical cases were randomly assigned 1:1 to the BIA non-invasive cerebral edema monitoring group and theImaging clinical examination（ICE) group. Cases that received surgical treatment were divided into two subgroups, the craniotomy group and the minimally invasive surgery group, depending on the type of surgery received, and of the two subgroups were randomly assigned in a 1 : 1 : 1 ratio to the invasive ICP monitoring group, the BIA technique noninvasive brain edema monitoring group, and the Imaging clinical examination（ICE） group. All the related investigative organization and individuals will obey the Declaration of Helsinki and Chinese Good Clinical Practice standard. A Data and Safety Monitoring Board (DSMB) will regularly monitor safety during the study.The trial has been approved by Institutional Review Board (IRB) and Ethics Committee(EC) in Xiangya Hospital Central South Uniersity.

Official Title
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The Effect of BIA Monitoring of Brainedemaontheneurological Prognosis of Supratentorial Massive Intracerebral Hemorrhage - A Randomized, Contrast，Multi-center Trial

Conditions
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Cerebral Hemorrhage, Hypertensive, Bioelectrical Impedance Analysis, Intracranial Hypertension, Monitoring, Critical Care, Treatment Outcome

Intervention / Treatment
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* Device: Non-invasive intracranial pressure monitoring
* Other: Parenchymal Intracranial pressure monitor
* Other: Treatment based on clinical and imaging observations


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years old and Age <80 years old. Diagnosed of a supratentorial spontaneous intracerebral hemorrhage. Diagnosis of supratentorial large-volume cerebral hemorrhage by CT or other imaging and meeting the diagnostic criteria for large-volume cerebral hemorrhage(hemorrhage volume ≥ 30 mL of supratentorial cerebral parenchymal hematoma volume according to the Coniglobus formula on the first CT scan at onset). Admission to study hospital within 48 hours of the disease. The family signed the informed consent. Exclusion Criteria: traumatic cerebral hemorrhage, cerebral amyloid angiopathy(CAA), secondary cerebral hemorrhage due to other specific etiologies (aneurysm, vascular malformation, smoker's disease, coagulopathy, aneurysmal stroke, vasculitis, cerebral venous thrombosis, hemorrhagic cerebral infarction, etc.) the presence of fixed bilateral dilated pupils on admission, no recovery of pupils after initial dehydration treatment, and very poor survival patients with extremely unstable vital signs after admission, with extremely poor prognosis and those considered non-viable, and patients whose families have abandoned follow-up treatment patients who are pregnant or lactating. patients with bilateral temporal skin ulceration, or subcutaneous hematoma in which monitoring electrode placement cannot be implemented the presence of other serious underlying diseases (intractable hypoxemia and circulatory failure with cardiopulmonary insufficiency that is difficult to correct by treatment, severe abnormal coagulation, severely reduced platelets, severe hepatic and renal insufficiency, combined neurodegenerative diseases, psychiatric diseases, autoimmune diseases, malignant tumors, thyroid diseases, etc.) the patient is agitated, coughing or choking too frequently, unable to be sedated or has difficulty in handling. those with mRS score > 2 before this onset.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bioelectrical impedance analysis(BIA) monitoring<br>Care based upon intracranial pressure and cerebral edema. | Device: Non-invasive intracranial pressure monitoring<br>* Treatment based on readings from Bioelectrical impedance analysis monitor（intracranial pressure and perturbation index (PI)）.<br>* Other names: low-frequency, bioelectrical, noninvasive brain edema monitor (Chongqing Born-Fruk Medical Equipment Co. Ltd, Chongqing, China;|
| Active Comparator: ICP monitoring<br>Care based upon intracranial pressure. | Other: Parenchymal Intracranial pressure monitor<br>* Treatment based on readings from Parenchymal intracranial pressure monitor.<br>* Other names: Integra Life Sciences Camino Intracranial Monitor;|
| Other: Usual Care<br>Treatment based on clinical and imaging without intracranial pressure monitoring. | Other: Treatment based on clinical and imaging observations<br>* Treatment based on clinical and imaging observations.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In a randomized controlled trial, test the effect on outcomes of management of severe supratentorial massive intracerebral hemorrhage guided by information from BIA monitors vs. ICP monitors and a standard empiric protocol. | Long-term outcome measures of neurological disability . mRS, NIHSS and Extended Glasgow Outcome Scale score. | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological recovery | The difference value of the NIHSS between Day 14/Day 90 and the baseline. | 90 days | 
| Correlation of edema quantification features | Comparison of the trend of brain edema coefficients monitored by the BIA technique with the quantitative features of 3D-Slice edema on CT images. | 14 days | 
| Modified Rankin scale | modified Rankin scale score, with score ranging from 0 (normal) to 6 (death), was used to evaluate the functional outcomes after ICH，good prognosis (mRS score 0-2), generally good prognosis (mRS score 3-4) , Poor prognosis (mRS >4 points). | 90 days | 
| Duration of ICU treatment | Time from the start of patient randomization to stable transfer out of the ICU. | 90 days | 
| GOS-E score | The difference value of the GOS-E between Day 14/Day 90，was used to evaluate the functional outcomes after ICH. | 90 days | 
| Quality of life score (EQ-5D) | Generic health status evaluated by EQ-5D questionnaire at the end of the therapy. | 90 days | 
| Length of hospitalization | Length of stay of patients throughout the treatment period since randomization. | 90 days | 
| The incidence of serious adverse events | The percentage of the Severity Adverse Events within the 14 days/90 days of the therapy. | 90 days | 
| Total mortality | All deaths reported post-randomization will be recorded and adjudicated | 90 days | 
| Adverse Events | The percentage of the Adverse Events during the therapy. | 90 days | 
| Severity Adverse Event | The percentage of the Severity Adverse Events within the 14 days of the therapy. | 14 days | 
| Total mortality | All deaths reported post-randomization will be recorded and adjudicated. Deaths will be subclassified by the adjudication committee as cardiovascular or non-cardiovascular. | 14 days | 
| Adverse Events | The percentage of the Adverse Events during the therapy. | 14 days | 
| The incidence of adverse events That are related to treatment | Incidence of complications that occurred during the use of invasive ICP or noninvasive cerebral edema monitoring after patient randomization. such as intracranial infection, probe displacement, recurrent intracranial hemorrhage, skin infection, etc. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spontaneous cerebral hemorrhage, Brain Edema, Bioelectrical impedance analysis, Intracranial Hypertension, Non-invasive intracranial pressure monitoring, Massive intracerebral hemorrhage, Treatment Outcome