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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Effects of Hydrogen/Oxygen Mixed Gas Inhalation for Patients With Coronavirus Disease 2019 (COVID-19) Who Had Dyspnea: A Multicenter, Open-label Clinical Trial

Conditions
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Covid-19, Hydrogen/Oxygen Mixed Gas, Dyspnea

Intervention / Treatment
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* Device: Hydrogen Oxygen Generator with Nebulizer
* Other: Standard-of-care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention Group<br>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<br>* 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.<br>Other: Standard-of-care<br>* Standard-of-care consisted of the supportive therapies (including oxygen therapy) recommended by the Chinese National Health Commission<br>|
| Other: Control Group<br>Usual care referred to the standard-of-care (including oxygen therapy) recommended by Chinese National Health Commission. | Other: Standard-of-care<br>* Standard-of-care consisted of the supportive therapies (including oxygen therapy) recommended by the Chinese National Health Commission<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with improved disease severity at day 2 | The proportion of patients with improved disease severity (by at least one scale) at day 2 | from baseline to day 2 | 
| The proportion of patients with improved disease severity at day 3 | The proportion of patients with improved disease severity (by at least one scale) at day 3 | from baseline to day 3 | 
| The proportion of patients with improved disease severity at the day before hospital discharge | The proportion of patients with improved disease severity (by at least one scale) at the day before hospital discharge | up to 14 days (from baseline to the day before hospital discharge) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in oxygen saturation at day 2. | The change from baseline in oxygen saturation at day 2. | from baseline to day 2 | 
| The change from baseline in oxygen saturation at day 3. | The change from baseline in oxygen saturation at day 3. | from baseline to day 3 | 
| The change from baseline in oxygen saturation at the day before hospital discharge | The change from baseline in oxygen saturation at the day before hospital discharge. | up to 14 days (from baseline to the day before hospital discharge) | 
| The change from baseline in dyspnea scale at day 2. | The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 | 
| The change from baseline in dyspnea scale at day 3. | The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 | 
| The change from baseline in dyspnea scale at 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. | up to 14 days (from baseline to the day before hospital discharge) | 
| The change from baseline in cough scale at day 2 | The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2 | from baseline to day 2 | 
| The change from baseline in cough scale at day 3 | The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3 | from baseline to day 3 | 
| The change from baseline in cough scale at 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 | up to 14 days (from baseline to the day before hospital discharge) | 
| The change from baseline in chest pain scale at day 2. | The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 | 
| The change from baseline in chest pain scale at day 3. | The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 | 
| The change from baseline in chest pain scale at 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. | up to 14 days (from baseline to the day before hospital discharge) | 
| The change from baseline in chest distress scale at day 2. | The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 | 
| The change from baseline in chest distress scale at day 3. | The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 | 
| The change from baseline in chest distress scale at 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. | up to 14 days (from baseline to the day before hospital discharge) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, Hydrogen/oxygen mixed gas, Dyspnea