Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)

Study Overview
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Brief Summary
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This is a multi-center, randomized, parallel controlled, double-blinded clinical trial to evaluate the effectiveness and safety of Hydrogen-Oxygen Generator with Nebulizer for adjuvant treatment of COVID-19 patients. The test group is expected to be superior to the control group in the primary endpoint (percentage of subjects achieving clinical recovery at Day 7 of study treatment). Subjects in the test group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects); and subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group).

Detailed Description
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Data of the following effectiveness and safety endpoints of subjects in the two groups will be collected and analyzed in this study, including of the primary effectiveness endpoint: percentage of subjects achieving clinical recovery at Day 7 of study treatment; and the secondary effectiveness endpoints: percentage of subjects achieving clinical recovery on Day 2, 3, 5, 10 of study treatment and that before discharge; percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more on Day 2, 3, 5, 7, 10 of study treatment and before discharge; reduction of WHO Clinical Progression Scale score on Day 2, 3, 5, 7, 10 of study treatment and before discharge; changes in COVID-19 symptom scores on Day 2, 3, 5, 7, 10 of study treatment and before discharge; total length of hospital stay; time from randomization to conversion to general COVID-19; time from randomization to conversion to mild COVID-19 disease; percentage of patients with no fever, shortness of breath and chest pain on Day 2, 3, 5, 7, 10 of study treatment and before discharge; Oxygen saturation based on finger blood samples in resting non-oxygen inhalation state; and safety evaluation variables including incidences of AEs, SAEs and device deficiencies.

Official Title
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A Multi-center, Randomized, Parallel Controlled, Double-Blinded Clinical Trial to Evaluate the Effectiveness and Safety of Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)

Conditions
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Covid19, Hydrogen-oxygen Gas, AMS-H-03

Intervention / Treatment
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* Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03
* Device: OLO-1 Medical Molecular Sieve Oxygen Generator


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects aged between 18 and 75 years old (inclusive). Diagnosed with mild, moderate or severe type of COVID-19 according to the criteria of Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (Trial Version 10). Positive result for COVID-19 nucleic acid test or rapid antigen detection at screening visit; Presenting with at least one respiratory symptom (e.g. dyspnoea, shortness of breath) at hospital admission. Be willing to participate in this trial and provide written informed consent form. Exclusion Criteria: Subjects with critical or asymptomatic type of COVID-19; Subjects with any known malignant tumor or life expectancy less than half a year. Subjects who are intolerable to inhalation treatment. Subjects with mental disorders or cognitive impairment who are unable to provide consent. Subjects with any immunodeficiency requiring chronic treatment with any corticosteroid or other immunosuppressants. Complicate with any serious cardiac, hepatic or renal disease (as indicated by aspartate aminotransferase [AST] and alanine aminotransferase [ALT] ≥ 2 × upper limit of normal [ULN], or creatinine ≥ 176.8mmol/L, or New York Heart Association (NYHA) Classification for heart failure of Class IV) or any serious primary systematic disease. Subjects who are going to use any non-expectorant antioxidant drug, including large doses of vitamin C and vitamin E during the study period. Subjects who are participating in any other clinical study on any investigational drug or medical device. Pregnant or lactating women. Subjects with any other condition judged as inappropriate to participate in this study by the 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects in the test group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects); subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental Group<br>Subjects in the experimental group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects); | Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03<br>* Subjects in the experimental group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects);<br>|
| Active Comparator: Control Group<br>subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group). | Device: OLO-1 Medical Molecular Sieve Oxygen Generator<br>* subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the percentage of subjects with clinical recovery on Day 7 of study treatment. | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | Day 7of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving clinical recovery | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | Day 2of study treatment | 
| Percentage of subjects achieving clinical recovery | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | Day 3 of study treatment | 
| Percentage of subjects achieving clinical recovery | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | Day 5of study treatment | 
| Percentage of subjects achieving clinical recovery | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | Day 10 of study treatment | 
| Percentage of subjects achieving clinical recovery | continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms ≤ 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms ≤ 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first). | through study completion, an average of 10 days | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Day 2 of study treatment | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Day 3 of study treatment | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Day 5 of study treatment | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Day 7 of study treatment | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Day 10 of study treatment | 
| Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more | The period from the beginning of treatment in patients enrolled to the time before discharge | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | Day 2 of study treatment | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | Day 3 of study treatment | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | Day 5 of study treatment | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | Day 7 of study treatment | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | Day 10 of study treatment | 
| Point reduction of WHO Clinical Progression Scale score | Point reduction of WHO Clinical Progression Scale score | The period from the beginning of treatment in patients enrolled to the time before discharge | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | Day 2 of the study treatment | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | Day 3 of the study treatment | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | Day 5 of the study treatment | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | Day 7 of the study treatment | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | Day 10 of the study treatment | 
| Changes in scores of COVID-19 related symptoms | Changes in scores of COVID-19 related symptoms | The period from the beginning of treatment in patients enrolled to the time before discharge | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Day 2 of the study treatment | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Day 3 of the study treatment | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Day 5 of the study treatment | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Day 7 of the study treatment | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Day 10 of the study treatment | 
| Percentage of subjects whose COVID-19 related symptoms have recovered to normal | Percentage of subjects whose COVID-19 related symptoms have recovered to normal | through study completion, an average of 10 days | 
| Total length of hospital stay | Total length of hospital stay | through study completion, an average of 14 days | 
| Time from randomization to conversion to mild type of COVID-19 | Time from randomization to conversion to mild type of COVID-19 | Time from randomization to conversion to mild type of COVID-19 | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | Day 2 of study treatment | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | Day 3 of study treatment | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | Day 5 of study treatment | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | Day 7 of study treatment | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | Day 10 of study treatment | 
| Oxygen saturation in resting non-oxygen inhalation state | Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group | through study completion, an average of 10 days | 
| CRP | C-reactive protein | Day 3 of study treatment | 
| CRP | C-reactive protein | Day 7 of study treatment | 
| CRP | C-reactive protein | Day 10 of study treatment | 
| CRP | C-reactive protein | through study completion, an average of 10 days | 
| IL-6 | IL-6 | Day 3 of study treatment | 
| IL-6 | IL-6 | Day 7 of study treatment | 
| IL-6 | IL-6 | Day 10 of study treatment | 
| IL-6 | IL-6 | through study completion, an average of 10 days | 
| ferritin | ferritin | Day 3 of study treatment | 
| ferritin | ferritin | Day 7 of study treatment | 
| ferritin | ferritin | Day 10 of study treatment | 
| ferritin | ferritin | through study completion, an average of 10 days | 
| lymphocytes | lymphocytes | Day 3 of study treatment | 
| lymphocytes | lymphocytes | Day 7of study treatment | 
| lymphocytes | lymphocytes | Day 10 of study treatment | 
| lymphocytes | lymphocytes | through study completion, an average of 10 days | 
| neutrophil to lymphocyte ratio | neutrophil to lymphocyte ratio | Day 3 of study treatment | 
| neutrophil to lymphocyte ratio | neutrophil to lymphocyte ratio | Day 7 of study treatment | 
| neutrophil to lymphocyte ratio | neutrophil to lymphocyte ratio | Day 10 of study treatment | 
| neutrophil to lymphocyte ratio | neutrophil to lymphocyte ratio | through study completion, an average of 10 days | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | Day 2 of study treatment | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | Day 3 of study treatment | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | Day 5 of study treatment | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | Day 7 of study treatment | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | Day 10 of study treatment | 
| Percentage of patients with fever, shortness of breath and chest pain all disappeared | Percentage of patients with fever, shortness of breath and chest pain all disappeared | through study completion, an average of 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid19, Hydrogen-oxygen Gas, AMS-H-03