Hydrogen/Oxygen Mixed Gas Inhalation for Coronavirus Disease 2019 (COVID-19)

• ClinicalTrials.gov Identifier: NCT04378712
• Recruitment Status: Completed
• First Posted: May 7, 2020
• Last Update Posted: May 15, 2020
• Sponsor: Guangzhou Institute of Respiratory Disease
• Information provided by (Responsible Party): Weijie Guan, Guangzhou Institute of Respiratory Disease

Study Description

Brief Summary:

This was a randomized, multi-center, open-label clinical trial. Eligible patients were recruited from seven hospitals in China. On the basis of standard-of-care, patients in treatment group inhaled H2-O2 (66% hydrogen; 33% oxygen) at 3 L/min via nasal cannula by using the Hydrogen/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditech Co., Ltd., China) until discharge. Patients in control group received standard-of-care (consisting of oxygen therapy) alone until discharge.

Condition or disease	Intervention/treatment	Phase
Covid-19; Hydrogen/Oxygen Mixed Gas; Dyspnea	Device: Hydrogen Oxygen Generator with Nebulizer; Other: Standard-of-care	Not Applicable

Detailed Description:

This was a randomized, multi-center, open-label clinical trial. Eligible patients were recruited from seven hospitals in China. On the basis of standard-of-care, patients in treatment group inhaled H2-O2 (66% hydrogen; 33% oxygen) at 3 L/min via nasal cannula by using the Hydrogen/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditech Co., Ltd., China) until discharge. Patients in control group received standard-of-care (consisting of oxygen therapy) alone until discharge. Clinical assessments included the five-category ordinal scale, four-category ordinary scale of dyspnea, coughing, chest distress and chest pain (0: None; 1: Mild; 2: Moderate; 3: Severe; 4: Very severe) and adverse events, performed on admission, at enrollment, at day 2 and 3 after randomization, and the day before discharge. The primary endpoint was the proportion of patients with improved disease severity (by at least one scale). Secondary endpoints comprised the change from baseline in oxygen saturation and symptom scales.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effects of Hydrogen/Oxygen Mixed Gas Inhalation for Patients With Coronavirus Disease 2019 (COVID-19) Who Had Dyspnea: A Multicenter, Open-label Clinical Trial
• Actual Study Start Date: January 21, 2020
• Actual Primary Completion Date: March 23, 2020
• Actual Study Completion Date: March 23, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention Group; H2-O2 (66% hydrogen; 33% oxygen) inhalation. Patients in treatment group inhaled H2-O2 (66% hydrogen; 33% oxygen) at 3 L/min via nasal cannula by using the Hydrogen/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditech Co., Ltd., China) until discharge.	Device: Hydrogen Oxygen Generator with Nebulizer; Patients in treatment group inhaled H2-O2 (66% hydrogen; 33% oxygen) at 3 L/min via nasal cannula by using the Hydrogen/Oxygen Generator (model AMS-H-03, Shanghai Asclepius Meditech Co., Ltd., China) until discharge.; Other: Standard-of-care; Standard-of-care consisted of the supportive therapies (including oxygen therapy) recommended by the Chinese National Health Commission
Control Group; Usual care referred to the standard-of-care (including oxygen therapy) recommended by Chinese National Health Commission.	Other: Standard-of-care; Standard-of-care consisted of the supportive therapies (including oxygen therapy) recommended by the Chinese National Health Commission

Outcome Measures

Primary Outcome Measures :

1. The proportion of patients with improved disease severity at day 2 [ Time Frame: from baseline to day 2 ]
   The proportion of patients with improved disease severity (by at least one scale) at day 2
2. The proportion of patients with improved disease severity at day 3 [ Time Frame: from baseline to day 3 ]
   The proportion of patients with improved disease severity (by at least one scale) at day 3
3. The proportion of patients with improved disease severity at the day before hospital discharge [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
   The proportion of patients with improved disease severity (by at least one scale) at the day before hospital discharge

Secondary Outcome Measures :

1. The change from baseline in oxygen saturation at day 2. [ Time Frame: from baseline to day 2 ]
   The change from baseline in oxygen saturation at day 2.
2. The change from baseline in oxygen saturation at day 3. [ Time Frame: from baseline to day 3 ]
   The change from baseline in oxygen saturation at day 3.
3. The change from baseline in oxygen saturation at the day before hospital discharge [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
   The change from baseline in oxygen saturation at the day before hospital discharge.
4. The change from baseline in dyspnea scale at day 2. [ Time Frame: from baseline to day 2 ]
   The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2.
5. The change from baseline in dyspnea scale at day 3. [ Time Frame: from baseline to day 3 ]
   The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3.
6. The change from baseline in dyspnea scale at the day before hospital discharge. [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
   The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge.
7. The change from baseline in cough scale at day 2 [ Time Frame: from baseline to day 2 ]
   The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2
8. The change from baseline in cough scale at day 3 [ Time Frame: from baseline to day 3 ]
   The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3
9. The change from baseline in cough scale at the day before hospital discharge [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
   The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge
10. The change from baseline in chest pain scale at day 2. [ Time Frame: from baseline to day 2 ]
    The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2.
11. The change from baseline in chest pain scale at day 3. [ Time Frame: from baseline to day 3 ]
    The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3.
12. The change from baseline in chest pain scale at the day before hospital discharge. [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
    The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge.
13. The change from baseline in chest distress scale at day 2. [ Time Frame: from baseline to day 2 ]
    The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2.
14. The change from baseline in chest distress scale at day 3. [ Time Frame: from baseline to day 3 ]
    The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3.
15. The change from baseline in chest distress scale at the day before hospital discharge. [ Time Frame: up to 14 days (from baseline to the day before hospital discharge) ]
    The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with lab-confirmed Covid-19 aged 18 to 75 years.
• Had dyspnea both on hospital admission and at enrollment.
• The patients volunteered to participate in this study and signed the informed consent

Exclusion Criteria:

• Have other systemic diseases other than COVID-19 -- a disease that, according to the investigator's judgment, might increase the risk of developing adverse outcomes or affect the outcome measures after participation in the study.

Women who are pregnant or breastfeeding or plan to be pregnant during the study.

Subjects with one of the following respiratory diseases:

• Subjects in critical or unstable conditions. Critical (meeting any of the following symptoms): 1. Respiratory failure occurs and mechanical ventilation is needed; 2. Shock occurs; 3. Other organ failure, ICU monitoring and treatment is needed.
• Having immunosuppressive diseases (HIV), severe neurological disease affecting upper respiratory tract control, or other risk factors that the investigator believes can cause a significant risk of pneumonia in subjects.
• Subjects with mental disorder and cognitive impairment.
• Subjects who do not follow the study steps.
• Patients with mental retardation, poor motivation, drug abuse (including drugs and alcohol) or other disease history restricting the effectiveness of informed consent in this study.
• Use of antioxidants, including large doses of vitamin C and vitamin E.
• Subjects who are not suitable for participation in this study in the judgment of investigator.

Contacts and Locations

Locations

China, Guangdong

First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Sponsors and Collaborators

Guangzhou Institute of Respiratory Disease

Investigators

• Principal Investigator: Wei-jie Guan, PhD; Guangzhou Institute of Respiratory Disease

More Information

Publications:

Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994. Erratum In: JAMA Intern Med. 2020 Jul 1;180(7):1031.

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available. Erratum In: Lancet Respir Med. 2020 Feb 25;:

Zhou ZQ, Zhong CH, Su ZQ, Li XY, Chen Y, Chen XB, Tang CL, Zhou LQ, Li SY. Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis. Respiration. 2019;97(1):42-51. doi: 10.1159/000492031. Epub 2018 Sep 18.

Morgan SE, Vukin K, Mosakowski S, Solano P, Stanton L, Lester L, Lavani R, Hall JB, Tung A. Use of heliox delivered via high-flow nasal cannula to treat an infant with coronavirus-related respiratory infection and severe acute air-flow obstruction. Respir Care. 2014 Nov;59(11):e166-70. doi: 10.4187/respcare.02728. Epub 2014 Aug 12.

Kneyber MC, van Heerde M, Markhorst DG, Plotz FB. Mechanical ventilation with heliox decreases respiratory system resistance and facilitates CO2 removal in obstructive airway disease. Intensive Care Med. 2006 Oct;32(10):1676-7. doi: 10.1007/s00134-006-0348-6. Epub 2006 Aug 23. No abstract available.

• Responsible Party: Weijie Guan, Associate professor of respiratory medicine, co-principal investigator, Guangzhou Institute of Respiratory Disease
• ClinicalTrials.gov Identifier: NCT04378712
• Other Study ID Numbers: JT202005LZ
• First Posted: May 7, 2020
• Last Update Posted: May 15, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Weijie Guan, Guangzhou Institute of Respiratory Disease:

Covid-19; Hydrogen/oxygen mixed gas; Dyspnea

Additional relevant MeSH terms:

COVID-19; Dyspnea; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory