Normobaric Hyperoxia for Intracerebral Hemorrhage

NCT ID: NCT04144868

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-15
• Study Completion Date: 2022-01-31

Brief Summary

Perihematoma edema (PHE), as the major injury for intracranial hemorrhage (ICH) involves more than the initial tissue damage induced directly by the hematoma. How to improve hypoxia in perihematoma seems to be a promising therapeutic candidate paradigm for ICH due to its pivotal role in the pathogenesis of perihematomas. Normobaric hyperoxia (NBO), supplied by a face mask (such as oxygen storage face mask) with atmosphere pressure (1ATA = 101.325 kPa, 100% O2), has been considered a safe, convenient, and promising therapy for correcting various diseases and thus garnered great attention in recent years. The previous study identified that early NBO could attenuate blood-brain barrier damage, rescue penumbra and finally improve the prognosis of ischemic stroke in patients with delayed rt-PA treatment. Therefore, given the profound effectiveness in the ischemic penumbra, we hypothesized that NBO might yield additional benefits for the ischemic-hypoxic tissues surrounding the hematoma in patients with ICH. Although many clinical trials have shown the effectiveness and safety of NBO in treating ischemic stroke, there is currently a lack of trials focusing on using NBO to treat ICH. Accordingly, we conducted a proof-of-concept, single-center, randomized controlled trial to evaluate the safety and efficacy of NBO in treating ICH patients so as to explore an innovative adjuvant therapy for ICH.

Detailed Description

Intracerebral hemorrhage (ICH) is an intractable and life-threatening stroke subtype that imposes a significant impact on people's well-being and quality of life. ICH-induced mechanical compression to the surrounding brain tissue is a major injury that increases intracranial pressure (ICP). High ICP can decrease cerebral blood flow (CBF) and influence cerebral metabolism in perihematoma and even the whole brain. Decreased aerobic metabolism and perfusion in perihematomal injury can exacerbate edema and enlarge hematoma. Moreover, secondary injury in the perihematoma, such as ischemia, oxidative stress, inflammatory response, and protease release, involves more than the initial tissue damage induced directly by the hematoma. Theoretically, low CBF and abnormal metabolism in ICH patients expose the brain tissue to the ischemic-hypoxic condition, which is similar to that in the ischemic penumbra in stroke. Therefore, the key to treating ICH is to find an approach that can rescue the perihematoma. Improving hypoxia in perihematoma seems to be a promising therapeutic candidate paradigm for ICH due to its pivotal role in the pathogenesis of perihematomas.

Normobaric hyperoxia (NBO), supplied by a face mask (such as oxygen storage face mask) with atmosphere pressure (1ATA = 101.325 kPa, 100% O2), has been considered a safe, convenient, and promising therapy for correcting various diseases and thus garnered great attention in recent years. The effectiveness of NBO on ischemic stroke (IS) has been fully identified. A plethora of studies show that NBO is capable of increasing the partial pressure of oxygen (PO2), elevating the blood flow and volume, protecting the blood-brain barrier (BBB), improving oxidative metabolism, reducing free radical damage, and even relieving inflammatory response in the penumbra. Rapid amelioration of hypoxia in brain tissue can restore brain dysfunction and improve clinical prognoses. Likewise, NBO is also regarded as a promising method for treating ICH. An animal study found that NBO for a period of 6 h per day for 3 consecutive days imposed a remarkable neuroprotective effect in rat ICH, improved neurological function, reduced brain edema, downregulated HIF-1α and VEGF expression and showed a reduction in apoptotic cells in the perihematoma. Although many clinical trials have shown the effectiveness and safety of NBO in treating ischemic stroke, there is currently a lack of trials focusing on using NBO to treat ICH. Accordingly, we conducted a proof-of-concept, single-center, randomized controlled trial to evaluate the safety and efficacy of NBO in treating ICH patients so as to explore an innovative adjuvant therapy for ICH.

Conditions

Normobaric Hyperoxia; Intracerebral Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

NBO group

Giving high-flow mask oxygen via oxygen storage face masks (100% O2, flow rate 8 L/min, 1 hour, four times daily, and 2 L/min via nasal catheter during intermittent periods, for 7 days) immediately at admission.

Group Type: EXPERIMENTAL

Oxygen storage face masks and nasal catheter

Intervention Type: DEVICE

Giving high-flow mask oxygen via oxygen storage face masks (100% O2, flow rate 8 L/min, 1 hour, four times daily, and 2 L/min via nasal catheter during intermittent periods, for 7 days) immediately at admission.

Control group

Giving 2 L/min flow of 100% O2 via nasal catheter at admission for 24 hours daily for 7 days.

Group Type: PLACEBO_COMPARATOR

Nasal catheter

Intervention Type: DEVICE

Giving 2 L/min flow of 100% O2 via nasal catheter at admission for 24 hours daily for 7 days.

Interventions

Oxygen storage face masks and nasal catheter

Giving high-flow mask oxygen via oxygen storage face masks (100% O2, flow rate 8 L/min, 1 hour, four times daily, and 2 L/min via nasal catheter during intermittent periods, for 7 days) immediately at admission.

Intervention Type: DEVICE

Nasal catheter

Giving 2 L/min flow of 100% O2 via nasal catheter at admission for 24 hours daily for 7 days.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. supratentorial hematomas confirmed by admitted cranial computed tomography (CT), with the volume ranging from 10 to 30 mL;

2. age 18-80 years;

3. National Institute of Health Stroke Scale (NIHSS) ≥ 6 and Glasgow Coma Scale (GCS) > 8 at admission;

4. onset-to-enrollment time ≤ 24 h;

5. signed informed consent.

Exclusion Criteria

1. a history of ICH, ischemic attack, brain tumor, brain trauma, and other intracranial injury or disorders;

2. pre-stroke modified ranking scales (mRS) ≥ 1;

3. life-threatening condition;

4. pre-stroke complicated with austere diseases such as cancer, heart failure, and respiratory failures;

5. severe liver and kidney disorders;

6. a history of respiratory diseases;

7. poor compliance;

8. participation in other clinical trials within the previous three months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiujiang University Affiliated Hospital

OTHER_GOV

Sponsor Role: collaborator

Capital Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ran Meng

Chief Physician, Head of the cerebral vein disease group. Principal Investigator, Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Xuanwu Hospital, Captial Medical University

Beijing, , China

Countries

China

References

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Reference Type: BACKGROUND

PMID: 25700288 (View on PubMed)

Ding J, Zhou D, Sui M, Meng R, Chandra A, Han J, Ding Y, Ji X. The effect of normobaric oxygen in patients with acute stroke: a systematic review and meta-analysis. Neurol Res. 2018 Jun;40(6):433-444. doi: 10.1080/01616412.2018.1454091. Epub 2018 Mar 30.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Xu Q, Fan SB, Wan YL, Liu XL, Wang L. The potential long-term neurological improvement of early hyperbaric oxygen therapy on hemorrhagic stroke in the diabetics. Diabetes Res Clin Pract. 2018 Apr;138:75-80. doi: 10.1016/j.diabres.2018.01.017. Epub 2018 Feb 3.

Reference Type: BACKGROUND

PMID: 29408705 (View on PubMed)

Shi SH, Qi ZF, Luo YM, Ji XM, Liu KJ. Normobaric oxygen treatment in acute ischemic stroke: a clinical perspective. Med Gas Res. 2016 Oct 14;6(3):147-153. doi: 10.4103/2045-9912.191360. eCollection 2016 Jul-Sep.

Reference Type: BACKGROUND

PMID: 27867482 (View on PubMed)

Liang J, Qi Z, Liu W, Wang P, Shi W, Dong W, Ji X, Luo Y, Liu KJ. Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment in cerebral ischemia. Stroke. 2015 May;46(5):1344-1351. doi: 10.1161/STROKEAHA.114.008599. Epub 2015 Mar 24.

Reference Type: BACKGROUND

PMID: 25804925 (View on PubMed)

Fujiwara N, Mandeville ET, Geng X, Luo Y, Arai K, Wang X, Ji X, Singhal AB, Lo EH. Effect of normobaric oxygen therapy in a rat model of intracerebral hemorrhage. Stroke. 2011 May;42(5):1469-72. doi: 10.1161/STROKEAHA.110.593350. Epub 2011 Mar 17.

Reference Type: BACKGROUND

PMID: 21415401 (View on PubMed)

You P, Lin M, Li K, Ye X, Zheng J. Normobaric oxygen therapy inhibits HIF-1alpha and VEGF expression in perihematoma and reduces neurological function defects. Neuroreport. 2016 Mar 23;27(5):329-36. doi: 10.1097/WNR.0000000000000542.

Reference Type: BACKGROUND

PMID: 26872098 (View on PubMed)

Xu H, Li R, Duan Y, Wang J, Liu S, Zhang Y, He W, Qin X, Cao G, Yang Y, Zhuge Q, Yang J, Chen W. Quantitative assessment on blood-brain barrier permeability of acute spontaneous intracerebral hemorrhage in basal ganglia: a CT perfusion study. Neuroradiology. 2017 Jul;59(7):677-684. doi: 10.1007/s00234-017-1852-9. Epub 2017 Jun 3.

Reference Type: RESULT

PMID: 28580533 (View on PubMed)

Chen Z, Ding J, Wu X, Bao B, Cao X, Wu X, Yin X, Meng R. Safety and efficacy of normobaric oxygenation on rescuing acute intracerebral hemorrhage-mediated brain damage-a protocol of randomized controlled trial. Trials. 2021 Jan 26;22(1):93. doi: 10.1186/s13063-021-05048-4.

Reference Type: DERIVED

PMID: 33499916 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NOTCH

Identifier Type: -

Identifier Source: org_study_id