Normobaric Hyperoxia for Intracerebral Hemorrhage

NCT04144868 | Completed Phase 2 Results DMC

• 1 other identifier: NOTCH
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

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.

Conditions

Normobaric Hyperoxia; Intracerebral Hemorrhage

Keywords

Intracerebral Hemorrhage; Normobaric Hyperoxia; Perihematomal Edema

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients With mRS 0-3

  modified Rankin Scale (mRS), an ordinal global disability scale ranging from 0 (no symptoms) to 6 (death)

  90 days

Secondary Outcomes (17)

• NIHSS Scores

  3 days

• NIHSS Scores

  7 days

• NIHSS Scores

  14 days

• Glasgow Coma Scale

  3 days

• Glasgow Coma Scale

  7 days

Study Arms (2)

NBO group

EXPERIMENTAL

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.

Device: Oxygen storage face masks and nasal catheter

Control group

PLACEBO COMPARATOR

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

Device: Nasal catheter

Interventions

Oxygen storage face masks and nasal catheter 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.

NBO group

Nasal catheter DEVICE

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

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• supratentorial hematomas confirmed by admitted cranial computed tomography (CT), with the volume ranging from 10 to 30 mL;
• age 18-80 years;
• National Institute of Health Stroke Scale (NIHSS) ≥ 6 and Glasgow Coma Scale (GCS) \> 8 at admission;
• onset-to-enrollment time ≤ 24 h;
• signed informed consent.

You may not qualify if:

• a history of ICH, ischemic attack, brain tumor, brain trauma, and other intracranial injury or disorders;
• pre-stroke modified ranking scales (mRS) ≥ 1;
• life-threatening condition;
• pre-stroke complicated with austere diseases such as cancer, heart failure, and respiratory failures;
• severe liver and kidney disorders;
• a history of respiratory diseases;
• poor compliance;
• participation in other clinical trials within the previous three months.

Sponsors & Collaborators

• Capital Medical University: lead
• Jiujiang University Affiliated Hospital: collaborator

Study Sites (1)

Xuanwu Hospital, Captial Medical University

Beijing, 100053, China

Location

Related Publications (11)

• McCourt R, Gould B, Kate M, Asdaghi N, Kosior JC, Coutts S, Hill MD, Demchuk A, Jeerakathil T, Emery D, Butcher KS. Blood-brain barrier compromise does not predict perihematoma edema growth in intracerebral hemorrhage. Stroke. 2015 Apr;46(4):954-60. doi: 10.1161/STROKEAHA.114.007544. Epub 2015 Feb 19.

  PMID: 25700288 BACKGROUND

• 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.

  PMID: 29600891 BACKGROUND

• Cai L, Stevenson J, Geng X, Peng C, Ji X, Xin R, Rastogi R, Sy C, Rafols JA, Ding Y. Combining Normobaric Oxygen with Ethanol or Hypothermia Prevents Brain Damage from Thromboembolic Stroke via PKC-Akt-NOX Modulation. Mol Neurobiol. 2017 Mar;54(2):1263-1277. doi: 10.1007/s12035-016-9695-7. Epub 2016 Jan 28.

  PMID: 26820681 BACKGROUND

• 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.

  PMID: 29408705 BACKGROUND

• 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.

  PMID: 27867482 BACKGROUND

• 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.

  PMID: 25804925 BACKGROUND

• 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.

  PMID: 21415401 BACKGROUND

• 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.

  PMID: 26872098 BACKGROUND

• 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.

  PMID: 28580533 RESULT

• Chen Z, Ding J, Bao B, Wu M, Cao X, Li W, Wu X, Xia Z, Xiang Y, Chen L, Liu H, Ji X, Yin X, Meng R. Normobaric hyperoxia for intracerebral hemorrhage: a randomized clinical trial. BMC Med. 2025 Dec 7;24(1):21. doi: 10.1186/s12916-025-04565-2.

  PMID: 41353144 DERIVED

• 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.

  PMID: 33499916 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Zhiying Chen
• Organization: Affiliated Hospital of Jiujiang University

zychenjj@jju.edu.cn

+86 13767263459

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigators and clinical assessors were blinded to the allocation, whereas the operators and participants were not. Neurological functional evaluations, imaging and laboratory tests were conducted by personnel blinded to the protocol of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician, Head of the cerebral vein disease group. Principal Investigator, Clinical Professor

Model Details: 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) or not (2 L/min via nasal catheter for 7 days) at admission.

Study Record Dates

• First Submitted: October 22, 2019
• First Posted: October 30, 2019
• Study Start: January 15, 2020
• Primary Completion: December 31, 2021
• Study Completion: January 31, 2022
• Last Updated: April 30, 2025
• Results First Posted: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)