Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Study Overview
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Brief Summary
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Intracerebral hemorrhage (ICH) is one of the most devastating nontraumatic cerebral vascular diseases. Its exacerbation is often related to a mass effect because of hematoma formation and edema in the perihematoma, which plays a key role in disease deterioration. Perihematoma edema is an important contributor to brain injuries secondary to ICH and one of the risk factors that leads to disease deterioration and high mortality. Brain edema following ICH was believed to be induced by the breakdown of the blood-brain barrier and ischemia and hypoxia of the perihematoma. Normobaric oxygen (NBO) therapy is a treatment that delivers high-flow oxygen at normobaric pressure through a facemask to supplement the oxygen supply,which maintain the oxygen concentration of typically 40-100% ,can increase the arterial oxygen content, and alleviate tissue hypoxia. NBO therapy has been shown to provide neuroprotection against ischemic stroke in an experimental study and a clinical trial. To the best of our knowledge, the potential of NBO therapy for neuroprotection against human hemorrhagic stroke has not been investigated. There are two studies about NBO interventions in the rat model of intracerebral hemorrhage.The one showed NBO did not worsen hemorrhage severity or brain edema. There were no significant differences in hemorrhagic blood volumes or brain water content. NBO did not affect any of the neurological outcome tests in the primary or secondary studies. Another one showed NBO groups improved NSSs,decreased contents of brain water, HIF-1α and VEGF, and fewer apoptotic cells in the perihematoma at 72 h after ICH compared with the ICH control group. These results suggest that NBO therapy with oxygen delivered at 90% conferred best neuroprotection to ICH rats, potentially through amelioration of brain edema by suppressing HIF-1α and VEGF expression in the perihematoma. But there is no clinical study on the safety and efficacy of NBO in patients with intracerebral hemorrhage.NBO has the advantages of simple operation, non-invasiveness and early application, which makes it have great application prospects in the treatment of ICH.

Official Title
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Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Conditions
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Normobaric Oxygen, Cerebral Hemorrhage

Intervention / Treatment
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* Other: Normobaric Oxygen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient Age ≥ 18 and ≤ 80 years; The diagnosis of ICH is confirmed by brain CT scan; NIHSS score ≥ 6 and GCS > 8 upon presentation; Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1 Signed and dated informed consent is obtained. Exclusion Criteria: Known history of severe chronic obstructive pulmonary disease (Forced Expiratory Vital Capacity less than 1.0L or oxygen dependent). New York Heart Association Class III heart failure. Patient will undergo surgical evacuation of ICH . Inability to undergo neuroimaging with MRI . GCS <8 Baseline mRS ≥ 2 Intraparenchymal hematoma secondary to rupture of cerebral aneurysm or bleeding of arteriovenous (A-V) malformation or cerebral tumors Any condition which, in the judgment of the investigator, might increase the risk to the patient.

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
Interventional Model Description: High-flow oxygen is delivered through the facemask at a rate of 8 L/min, once a hour, every 4 hours to the ICH patient.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: NBO group<br>For eligible patients into the group of cerebral hemorrhage,Low-flow oxygen is delivered through the facemask at a rate of 8 L/min, once a hour, every 4 hours. Regular treatment is based on associated guidelines for ICH . | Other: Normobaric Oxygen<br> <br> |
| No Intervention: Control group<br>Low-flow oxygen is delivered through the facemask at a rate of 2 L/min, once a hour, every 4 hours. Regular treatment is based on associated guidelines for ICH . | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of death or major disability |  | 90 days after the onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the midline shift from the initial to follow-up CT/MRI scans |  | Day0, Day1,Day3,Day7,Day14 | 
| The change in the volume of ICH from the initial to follow-up CT/MRI scans |  | Day0, Day1,Day3,Day7,Day14 | 
| The change of cerebral blood flow in perihematomal lesions follow-up CTP scans |  | Day0, Day1,Day7 | 
| The evaluation of neurological impairment caused by a stroke | National Institute of Health stroke scale(NIHSS),The score ranges from 0 to 42. The higher the score, the more severe the nerve damage. | Day0, Day1,Day3,Day7,Day90 | 
| Neurological function outcome | The modified Rankin scale is used to measure the recovery of neurological function in patients after stroke. The score range is from 0 to 5. The higher the score, the worse the neurological function is restored. We need to calculate the proportion of the modified Rankin scale 0-2. | Day90 | 
| The evaluation of serum biomarkers | We used ELISA kits to detect the lebvels of neuron - specific enolase (NSE) ， matrix metalloprotease 9 (MMP-9)， reactive oxygen species (ROS) and hypoxia-inducing factor 1a (HIF-1a) in blood. The results were measured in ng/ml. | Day0, Day1,Day3,Day7,Day14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cerebral Hemorrhage, Normobaric oxygen therapy, Mask oxygen, edema