Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of COVID-19 Positive Patients

Study Overview
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Brief Summary
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This is a prospective, multicenter, randomized, controlled, superiority clinical trial. It is expected that the test group would have better effectiveness than the control group in the primary evaluation indicator (time to negative viral nucleic acid detection from the start of study treatment). The test group will use the investigational medical device Hydrogen-Oxygen Generator with Nebulizer (Shanghai Asclepius Meditec Co., Ltd.) + basic treatment (the investigator provides corresponding symptomatic support treatment based on the condition of the patients), and the control group will use the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen) + basic treatment, to evaluate the effectiveness and safety of the investigational medical device Hydrogen-Oxygen Generator with Nebulizer for adjuvant treatment of COVID-19 patients.

Detailed Description
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A total of 188 subjects who met the requirements of this study will be randomized into the test group or the control group in a 1:1 ratio to receive treatment, and the subjects will be observed and evaluated in the period from treatment after enrollment to discharge. All enrolled subjects will receive treatment and visit, including screening visit (within 3 days before enrollment), randomization and treatment visit (Day 0), 1, 2, 3, 5, 7, 10, and discharge visit after treatment. The primary effectiveness evaluation indicator (time to negative viral nucleic acid detection from the start of the study treatment), the secondary effectiveness evaluation indicators (viral nucleic acid negative conversion rate, imaging evaluation, inflammatory indicators such as CRP, IL-6, lymphocytes, clinical response rate at 7 days of treatment, recovery rate and recovery time of major symptoms, index oxygen saturation, and Ct value of nucleic acid detection), and safety evaluation indicators ( incidence of AE and SAE, incidence of device deficiencies) of the two groups will be collected and analyzed.

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

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: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged between 18 and 80 years old (inclusive). Diagnosed as general type of COVID-19 according to the criteria of Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (Trial Version 9). Subjects who are willing to participate and provided written informed consent form. Exclusion Criteria: Diagnosed as mild, severe, critical or asymptomatic type of COVID-19. Subjects in the treatment or active stage of malignant tumor. 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 serious primary diseases such as heart, liver, kidney, and hematopoietic diseases; acute exacerbation phase of chronic obstructive pulmonary disease, or acute attack of bronchial asthma. Subjects who are using any non-expectorant antioxidant drug, including large doses of vitamin C and vitamin E. Subjects who are participating any other clinical study of any investigational drug or medical device. Pregnant or lactating women. 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: 80 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: The test group will use the investigational medical device Hydrogen-Oxygen Generator with Nebulizer (Shanghai Asclepius Meditec Co., Ltd.) + basic treatment (the investigator provides corresponding symptomatic support treatment based on the condition of the patients), and the control group will use the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen) + basic treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental Group<br>The test group will use the investigational medical device Hydrogen-Oxygen Generator with Nebulizer (Shanghai Asclepius Meditec Co., Ltd.) + basic treatment (the investigator provides corresponding symptomatic support treatment based on the condition of the patients) | Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03<br>* The experimental group used the experimental medical device Hydrogen-Oxygen Generator with Nebulizer(Shanghai Asclepius Meditec Co., Ltd. ) The flow rate was 3L/min, and the cumulative treatment time was not less than 6 hours per day.<br>|
| Active Comparator: Control Group<br>The control group will use the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen) + basic treatment | Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)<br>* the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen). The flow rate was 3L/min, and the cumulative treatment time was not less than 6 hours per day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to negative viral nucleic acid detection from the start of the study treatment. | Time to negative viral nucleic acid detection is defined as two consecutive negative viral nucleic acid detections of respiratory specimens (samples will be taken at least 24 hours apart). | through study completion, The average time from enrollment to two consecutive negative nucleic acid tests of respiratory specimens (sampling time interval of at least 24 hours) was approximately 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Negative rate based on viral nucleic acid detection | Negative viral nucleic acid detection is defined as two consecutive negative nucleic acid detections of respiratory specimens (the sampling time interval will be at least 24 hours). | The negative rate of viral nucleic acid detection from 3, 5, 7, 10 days after the treatment to discharge will be analyzed. | 
| Imaging evalution indicators | Significant lesion absorption >50%, lesion absorption degree of 10%-50%, lesion absorption degree of < 10%, and lesion progression compared with that at enrollment as showed in lung imaging. | Lung imaging changes were analyzed on the 3rd and 7th day after treatment. | 
| CRP | Inflammatory indicators such as CRP | The changes were compared with those on day 3, 5 and 7 before treatment. | 
| Clinical effectiveness within 7 days | Clinically effective is defined as cured + significant effective + effective. Clinical response rate = (total number of patients of cured + significant effective + effective)/total number of subjects included in the analysis ×100%. It should be noted that in the actual situation, some clinical symptoms or signs may still be observed in the follow up after the end of treatment. If it is indicated that the above situation is resulted from the underlying disease, the investigator can also consider the patient to be clinically cured after comprehensive judgment based on the clinical data. | The clinical effective rate after 7 days of treatment will be used as the evaluation indiactor | 
| recovery rate and time to recovery of main symptoms | It is defined as all major symptoms (fever, fatigue, cough, expectoration, chest tightness, chest pain, shortness of breath, and dyspnea) at enrollment had all disappeared or completely returned to normal at follow up. | The patients will be followed up at 3, 5, 7, 10 days after the treatment and at discharge visit. | 
| Oxygen saturation | Oxygen saturation | This will be evaluated at 3, 5, 7, and 10 days after the treatment and at discharge. The oxygen saturation will be measured at rest after stopping oxygen or hydrogen inhalation for 10 minutes. | 
| Ct value in nucleic acid detection | Ct value in nucleic acid detection | This will be evaluated at1,2，3, 5, 7, and 10 days after the treatment and at discharge. | 
| IL-6 | Inflammatory indicators such as IL-6 | The changes were compared with those on day 3, 5 and 7 before treatment. | 
| lymphocytes | Inflammatory indicators such as lymphocytes | The changes were compared with those on day 3, 5 and 7 before treatment. | 

 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