Efficacy and Safety of NeuroEndoscopic Surgery for IntraCerebral Hemorrhage (NESICH)

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

To compare the efficacy and safety of neuroendoscopic hematoma removal and standard conservative treatment for patients with spontaneous supratentorial deep intracerebral hemorrhage.

Study Overview

• Status: Recruiting
• Conditions: Intracerebral Hemorrhage Basal Ganglia (Diagnosis)
• Intervention / Treatment: Procedure: Endoscopic surgery; Other: Medical management

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

• Study Type: Interventional
• Enrollment (Anticipated): 560
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rong Hu, MD; Phone Number: 8615123917123; Email: huchrong@aliyun.com
• Study Contact Backup: Name: Hua Feng, MD; Phone Number: 8613708321681; Email: fenghua201818@aliyun.com

Study Locations

• China
  • Ganzhou, China
    • Recruiting
    • Ganzhou city people's Hospita
    • Contact: Yun X Ye, MD
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Recruiting
      • Chongqing Emergency Medical Center
      • Contact: Bing y Deng, MD
  • Hubei
    • Hubei, Hubei, China, 441000
      • Recruiting
      • Xiang Yang No.1 Peoples Hospital
      • Contact: Hua Cu Fu, MD; Phone Number: 15172552710; Email: nianbeifch@163.com
  • Sichuan
    • Sichuan, Sichuan, China, 635100
      • Recruiting
      • Dazhu County People's Hospital
      • Contact: sheng zhu, MD; Phone Number: +8615882911301; Email: 371773434@qq.com
      • Principal Investigator: sheng zhu, MD PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient age ≥ 18 and ≤ 80.
2. 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.
3. Spontaneous supratentorial deep ICH ≥25 ml (deep location involving the basal ganglia, thalamus, internal capsule, or deep periventricular white matter).
4. 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 )
5. Glasgow Coma Scale（GCS） ≥ 5 and ≤ 14, National Institutes of Health Stroke Scale（NIHSS） ≥ 6.
6. Historical Rankin score of 0 or 1.
7. Systolic blood pressure（SBP） <180 mmHg sustained for six hours recorded closest to the time of randomisation.
8. Randomization must be done within 24 hours after dCT.
9. Written informed consent must be obtained from patients or their relatives.

Exclusion Criteria:

1. Ruptured aneurysm, arteriovenous malformation (AVM), vascular anomaly, Moyamoya disease, mass or tumor, trauma, haemorrhagic conversion of an ischemic infarct, diagnosed with radiographic imaging.
2. Infratentorial hemorrhage, primary thalamic ICH, lobar ICH, primary Intraventricular hemorrhage.
3. Hematoma with apparent midbrain extension with third nerve palsy or dilated and non-reactive pupils. Other (supranuclear) gaze abnormalities are not exclusions.
4. 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.
5. Multiple hemorrhages. Defined as 2 or more separate hematomas in multiple location (lobar, deep, brain stem, cerebellum, subdural hemorrhage, subarachnoid hemorrhage).
6. Intraventricular hemorrhage（IVH) is visually estimated to involve >50% of either of the lateral ventricles.
7. Subjects requiring long-term anti-coagulation are excluded.
8. Use of dabigatran, apixaban, and/or rivaroxaban (or a similar medication from the similar medication class) prior to symptom onset.
9. Any irreversible coagulopathy or known clotting disorder.
10. Platelet count <1,000,000;International Normalized Ratio (INR) >1.4.
11. 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).
12. Irreversible impaired brain stem function (bilateral fixed, dilated pupils and extensor motor posturing).
13. Recurrence of a recent (<1 year) hemorrhage.
14. History of surgery or any parenchymal or other intracranial arachnoid hemorrhage, subdural or extradural hemorrhage within the past 30 days.
15. There was a history of uncompleted haemorrhage in the past, such as gastrointestinal bleeding, urogenital bleeding and respiratory bleeding.
16. History of myocardial infarction within the past 30 days.
17. 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.
18. Patients with severe hepatic impairment, such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels exceed 3 times upper limit of normal.
19. Patients with severe renal insufficiency (estimated glomerular filtration rate <=30ml / min/1.73 m2) or patients receiving continuous renal replacement therapy, hemodialysis, peritoneal dialysis.
20. Before randomization, Systolic blood pressure(SBP) could not be effectively controlled below 180 mmHg after active antihypertensive therapy.
21. patients with mental illness or cognitive impairment limiting their ability to complete follow-up plan.
22. Any concurrent serious illness that would interfere with the outcome assessments including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrine, immunologic, and hematologic disease.
23. 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.
24. Allergy/sensitivity to surgery-related drugs (anesthesia, antibiotic), surgical instruments, contrast agent.
25. Pregnant or nursing mothers and female expecting to become pregnant within one year.
26. End-stage any disease or known life-expectancy of less than 6 months.
27. Any other conditions that the investigator believes it would pose a significant hazard to the subject if the investigational therapy were initiated.
28. 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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.

Collaborators and Investigators

• Sponsor: Southwest Hospital, China
• Investigators: Study Chair: Rong Hu, MD, PLA Army Medical University

Publications and helpful links

General Publications

• Hansen BM, Ullman N, Muschelli J, Norrving B, Dlugash R, Avadhani R, Awad I, Zuccarello M, Ziai WC, Hanley DF, Thompson RE, Lindgren A; MISTIE and CLEAR Investigators. Relationship of White Matter Lesions with Intracerebral Hemorrhage Expansion and Functional Outcome: MISTIE II and CLEAR III. Neurocrit Care. 2020 Oct;33(2):516-524. doi: 10.1007/s12028-020-00916-4.
• de Oliveira Manoel AL. Surgery for spontaneous intracerebral hemorrhage. Crit Care. 2020 Feb 7;24(1):45. doi: 10.1186/s13054-020-2749-2.
• Anderson CD, James ML. Survival and independence after intracerebral hemorrhage: Trends and opportunities. Neurology. 2018 Jun 5;90(23):1043-1044. doi: 10.1212/WNL.0000000000005625. Epub 2018 May 4. No abstract available.
• Kuo LT, Chen CM, Li CH, Tsai JC, Chiu HC, Liu LC, Tu YK, Huang AP. Early endoscope-assisted hematoma evacuation in patients with supratentorial intracerebral hemorrhage: case selection, surgical technique, and long-term results. Neurosurg Focus. 2011 Apr;30(4):E9. doi: 10.3171/2011.2.FOCUS10313.
• Kellner CP, Song R, Pan J, Nistal DA, Scaggiante J, Chartrain AG, Rumsey J, Hom D, Dangayach N, Swarup R, Tuhrim S, Ghatan S, Bederson JB, Mocco J. Long-term functional outcome following minimally invasive endoscopic intracerebral hemorrhage evacuation. J Neurointerv Surg. 2020 May;12(5):489-494. doi: 10.1136/neurintsurg-2019-015528. Epub 2020 Jan 8.
• Xu X, Chen X, Li F, Zheng X, Wang Q, Sun G, Zhang J, Xu B. Erratum. Effectiveness of endoscopic surgery for supratentorial hypertensive intracerebral hemorrhage: a comparison with craniotomy. J Neurosurg. 2018 Feb;128(2):649. doi: 10.3171/2017.5.JNS161589a. Epub 2017 Jul 28. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2022
• Primary Completion (Anticipated): September 1, 2025
• Study Completion (Anticipated): September 1, 2026

Study Registration Dates

• First Submitted: September 4, 2022
• First Submitted That Met QC Criteria: September 12, 2022
• First Posted (Actual): September 14, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 28, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Intracerebral hemorrhage; NeuroEndoscopic Surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Cysts; Connective Tissue Diseases; Mucinoses; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Ganglion Cysts
• Other Study ID Numbers: (A)KY2022103

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