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

Tracking Information

• First Submitted Date: April 29, 2020
• First Posted Date: May 7, 2020
• Last Update Posted Date: May 15, 2020
• Actual Study Start Date: January 21, 2020
• Actual Primary Completion Date: March 23, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 5, 2020)

• 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
• 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
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 5, 2020)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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
• 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
• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Hydrogen/Oxygen Mixed Gas Inhalation for Coronavirus Disease 2019 (COVID-19)
• 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
• 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.
• 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 Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Covid-19
• Hydrogen/Oxygen Mixed Gas
• Dyspnea

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Device: Hydrogen Oxygen Generator with Nebulizer
  • Other: Standard-of-care
• Control Group
  Usual care referred to the standard-of-care (including oxygen therapy) recommended by Chinese National Health Commission.
  Intervention: Other: Standard-of-care

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 5, 2020): 90
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: March 23, 2020
• Actual Primary Completion Date: March 23, 2020 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04378712
• Other Study ID Numbers: JT202005LZ
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Weijie Guan, Guangzhou Institute of Respiratory Disease
• Original Responsible Party: Same as current
• Current Study Sponsor: Guangzhou Institute of Respiratory Disease
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Guangzhou Institute of Respiratory Disease
• Verification Date: May 2020