Efficacy and Safety of NeuroEndoscopic Surgery for IntraCerebral Hemorrhage

Study Overview
=================
Brief Summary
-----------------
To compare the efficacy and safety of neuroendoscopic hematoma removal and standard conservative treatment for patients with spontaneous supratentorial deep intracerebral hemorrhage.

Detailed Description
-----------------
Neuroendoscopic treatment of spontaneous intracerebral hemorrhage (ICH) is more and more widely used, but multi-center clinical study on the efficacy and safety of neuroendoscopic treatment of ICH is relatively small. Based on the lack of sufficient clinical evidence, the investigators plan to conduct a prospective, multicenter, randomized controlled clinical trial to investigate the safety and efficacy of neuroendoscopy in the treatment of spontaneous cerebral parenchymal hemorrhage, so as to provide evidence-based medical evidence for endoscopic minimally invasive treatment of cerebral hemorrhage and its application.The aim of trial was to determine whether the endoscopic surgery could achieve the benefits of clot evacuation and improve functional outcome at 180 days after ICH without procedure-related safety events or additional brain injury beyond the risks associated with standard care

Official Title
-----------------
Efficacy and Safety of NeuroEndoscopic Surgery for IntraCerebral Hemorrhage: a Randomised, Controlled, Open-label, Blinded Endpoint Trial

Conditions
-----------------
Intracerebral Hemorrhage Basal Ganglia (Diagnosis)

Intervention / Treatment
-----------------
* Procedure: Endoscopic surgery
* Other: Medical management


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient age ≥ 18 and ≤ 80. Symptoms less than 24 hours prior to diagnostic CT scan. For an unknown time of onset, use the time the patient was last known to be well. Spontaneous supratentorial deep ICH ≥25 ml (deep location involving the basal ganglia, thalamus, internal capsule, or deep periventricular white matter). The stability of the hematoma was determined by CT angiogram (CTA) examination. If the spot sign is positive, repeat CT scan at least 6 hours after diagnostic CT (dCT) showing clot stability (growth <5 ml). (If the clot volume measured on this stability CT scan increases by 5 ml or more, a second stability determination is allowed by repeat CT scan at least 6 hours later, until the randomization time window is closed ) Glasgow Coma Scale（GCS） ≥ 5 and ≤ 14, National Institutes of Health Stroke Scale（NIHSS） ≥ 6. Historical Rankin score of 0 or 1. Systolic blood pressure（SBP） <180 mmHg sustained for six hours recorded closest to the time of randomisation. Randomization must be done within 24 hours after dCT. Written informed consent must be obtained from patients or their relatives. Exclusion Criteria: Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, mass or tumor, trauma, haemorrhagic conversion of an ischemic infarct, diagnosed with radiographic imaging. Infratentorial hemorrhage, primary thalamic ICH, lobar ICH, primary Intraventricular hemorrhage. Hematoma with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions. Patients with life-threatening mass effect caused by hematoma (e.g., CT showed midline deviation of more than 1cm, cisterna ambient compression disappeared), or patients whose condition was considered to be unstable and not suitable for inclusion. Multiple hemorrhages. Defined as 2 or more separate hematomas in multiple location (lobar, deep, brain stem, cerebellum, subdural hemorrhage, subarachnoid hemorrhage). Intraventricular hemorrhage（IVH) is visually estimated to involve >50% of either of the lateral ventricles. Subjects requiring long-term anti-coagulation are excluded. Use of dabigatran, apixaban, and/or rivaroxaban (or a similar medication from the similar medication class) prior to symptom onset. Any irreversible coagulopathy or known clotting disorder. Platelet count <1,000,000;International Normalized Ratio (INR) >1.4. Inability to sustain INR ≤1.4 using short- and long-acting procoagulants (such as but not limited to NovoSeven, Fresh frozen plasma（FFP）, and/or vitamin K). Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing). Recurrence of a recent (<1 year) hemorrhage. History of surgery or any parenchymal or other intracranial arachnoid hemorrhage, subdural or extradural hemorrhage within the past 30 days. There was a history of uncompleted haemorrhage in the past, such as gastrointestinal bleeding, urogenital bleeding and respiratory bleeding. History of myocardial infarction within the past 30 days. Known risk for embolisation, including history of left heart thrombus, mitral stenosis with atrial fibrillation, acute pericarditis, or subacute bacterial endocarditis. Atrial fibrillation without mitral stenosis is permitted. Patients with severe hepatic impairment, such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceed 3 times upper limit of normal. Patients with severe renal insufficiency (estimated glomerular filtration rate <=30ml / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis. Before randomization, Systolic blood pressure(SBP) could not be effectively controlled below 180 mmHg after active antihypertensive therapy. patients with mental illness or cognitive impairment limiting their ability to complete follow-up plan. Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrine, immunologic, and hematologic disease. Active drug or alcohol use or dependence that, or poor compliance due to other reasons, in the opinion of the site investigator, would interfere with adherence to study requirements. Allergy/sensitivity to surgery-related drugs (anesthesia, antibiotic), surgical instruments, contrast agent. Pregnant or nursing mothers and female expecting to become pregnant within one year. End-stage any disease or known life-expectancy of less than 6 months. Any other conditions that the investigator believes it would pose a significant hazard to the subject if the investigational therapy were initiated. Participation in a concurrent interventional medical investigation or clinical trial. Patients in observational, natural history, and/or epidemiological studies not involving an intervention are eligible

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Arm<br>Endoscopic surgery | Procedure: Endoscopic surgery<br>* Subjects will receive surgical hematoma evacuation using neuroendoscope, followed by medical management<br>|
| Active Comparator: Control Arm<br>Medical management | Other: Medical management<br>* Subjects will initially receive the standard medical therapies for the treatment of intracerebral hemorrhage, according to the latest available guideline.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with Modified Rankin Scale (mRS) score 0-3 | Functional outcome (comparing the intervention group to the control), assessed with the modified Rankin Scale (mRS) at 6 months.The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. | 180 days | 
| Safety outcome | All cause mortality from onset to 180 days | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glasgow Outcome Scale Extended (GOS-E) | GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. | 30 days. | 
| Glasgow Outcome Scale Extended (GOS-E) | GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. | 90 days. | 
| Glasgow Outcome Scale Extended (GOS-E) | GOS-E subdivides the categories of severe and moderate disability and good recovery using a scale of 1 to 8 where 1 = death, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery. Structured telephone interviews have been developed and validated for the GOS-E and these questions were incorporated into the follow-up survey. GOS-E was dichotomized into unfavorable (1 to 4) and favorable (5 to 8) outcomes. | 180 days. | 
| Modified Rankin Scale (mRS) Score | The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. | 30 days. | 
| Modified Rankin Scale (mRS) Score | The mRS is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. It is scored from: 0=No symptoms at all, 1=No significant disability, 2=Slight disability, 3=Moderate disability, 4=Moderately severe disability, 5=Severe disability and 6=death. | 90 days . | 
| Survival rate | comparing the intervention group to the control | 30 days. | 
| Survival rate | comparing the intervention group to the control | 90 days. | 
| Assessment of cognitive function with Mini-Mental State Examination (MMSE) | The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. | 30 days. | 
| Assessment of cognitive function with Mini-Mental State Examination (MMSE) | The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. | 90 days. | 
| Assessment of cognitive function with Mini-Mental State Examination (MMSE) | The MMSE is a screening test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language); the total score can range from 0 to 30, with a higher score indicating better function. | 180 days. | 
| Quality of life measured with the 5-level EQ-5D (EQ-5D-5L) | The EQ-5D-5L is a standard measure of health-related quality of life.EQ-5D-5L consists of two components: a health state profile and a visual analog scale (VAS). EQ-5D health state profile comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where a higher score indicates a better health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating the worst health you can imagine and 100 indicating the best health you can imagine. Higher scores of EQ VAS indicate better health. | 30 days. | 
| Quality of life measured with the 5-level EQ-5D (EQ-5D-5L) | The EQ-5D-5L is a standard measure of health-related quality of life.EQ-5D-5L consists of two components: a health state profile and a visual analog scale (VAS). EQ-5D health state profile comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where a higher score indicates a better health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating the worst health you can imagine and 100 indicating the best health you can imagine. Higher scores of EQ VAS indicate better health. | 90 days. | 
| Quality of life measured with the 5-level EQ-5D (EQ-5D-5L) | The EQ-5D-5L is a standard measure of health-related quality of life.EQ-5D-5L consists of two components: a health state profile and a visual analog scale (VAS). EQ-5D health state profile comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. The 5D-5L systems are converted into a single index utility score between 0 to 1, where a higher score indicates a better health state. The VAS records the participant's health on a 0-100 mm VAS scale, with 0 indicating the worst health you can imagine and 100 indicating the best health you can imagine. Higher scores of EQ VAS indicate better health. | 180 days. | 
| Length of ICU | Duration of stay in the ICU | Number of days from admission, up to 180 days | 
| Length of hospitalization | Duration of stay in the hospital | Number of days from admission to discharge, up to 180 days | 
| In-hospital cost | all medical cost during the in-hospital period | Number of days from admission to discharge, up to 180 days | 
| Evacuation rate of hematoma and residual hematoma volume after surgery, as well as their relationships with functional outcome. | This parameter will be monitored by CT scan immediately after the surgery | 7 days. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intracerebral hemorrhage, NeuroEndoscopic Surgery