Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Sponsor

Capital Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT04144868

Collaborator

(none)

100

Enrollment

Location

Arms

Anticipated Duration (Months)

7.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Normobaric Oxygen Cerebral Hemorrhage	Other: Normobaric Oxygen	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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 (Participant, Care Provider)

Primary Purpose:

Treatment

Official Title:

Safety and Efficacy of NBO in Acute Intracerebral Hemorrhage

Anticipated Study Start Date :

Oct 30, 2019

Anticipated Primary Completion Date :

Aug 8, 2020

Anticipated Study Completion Date :

Dec 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: NBO group 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
No Intervention: Control group 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 .

Arm

Intervention/Treatment

Experimental: Experimental: NBO group

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

No Intervention: Control group

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 .

Outcome Measures

Primary Outcome Measures

The proportion of death or major disability [90 days after the onset]

Secondary Outcome Measures

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 [Day0, Day1,Day3,Day7,Day90]
National Institute of Health stroke scale(NIHSS),The score ranges from 0 to 42. The higher the score, the more severe the nerve damage.
Neurological function outcome [Day90]
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.
The evaluation of serum biomarkers [Day0, Day1,Day3,Day7,Day14]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Xuanwu Hospital, Captial Medical University	Beijing		China	100053

Sponsors and Collaborators

Capital Medical University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Ran Meng, Chief Physician, Head of the cerebral vein disease group. Principal Investigator, Clinical Professor, Capital Medical University

ClinicalTrials.gov Identifier:

NCT04144868

Other Study ID Numbers:

NBO-ICH

First Posted:

Oct 30, 2019

Last Update Posted:

Oct 30, 2019

Last Verified:

Oct 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Ran Meng, Chief Physician, Head of the cerebral vein disease group. Principal Investigator, Clinical Professor, Capital Medical University

Cerebral Hemorrhage

Normobaric oxygen therapy

Mask oxygen

edema

Additional relevant MeSH terms:

Cerebral Hemorrhage

Hemorrhage

Study Results

No Results Posted as of Oct 30, 2019