Clinical trial NCT04336462: Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19
Official title: A Multi-center, Randomized, Parallel-Controlled Clinical Trial of the Application of A Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: COVID-19
Keywords: Hydrogen-Oxygen Generator with Neburlizer
COVID-19
Lead sponsor: Shanghai Asclepius Meditec Inc.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Public Health Clinical Center
name: Henan Provincial People's Hospital
name: Shenzhen Third People's Hospital
name: The First People's Hospital of Yunnan
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: Shanghai 6th People's Hospital
name: Guangdong Provincial Hospital of Traditional Chinese Medicine
First posted: 2020-04-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the efficacy and safety of Hydrogen-Oxygen Generator with Nebulizer (model AMS-H-03) developed by Shanghai Asclepius Meditech Co., Ltd. as an adjuvant therapy for the patients with COVID-19 infected pneumonia in improving the clinical symptoms and reducing the incidence of severe pneumonia, as compared with the reference device of EverFlo Oxygen Concentrator (registration certificate No.: NMPA Registration Standard: 20162542389) manufactured by Respironics, Inc. US.

Detailed description: A multi-center, randomized, parallel-controlled clinical trial design is used in this study.

Eligible subjects will be randomized into the study group and control group in a 1:1 ratio. In addition to the supportive treatments depending on the condition, the subjects in the study group will inhale the mixed gas of hydrogen/oxygen (hydrogen concentration 66%, oxygen concentration 33%) at a flow rate of 6 L/min every day using the Hydrogen/Oxygen Generator with Nebulizer (model AMS-H-03) developed by Shanghai Asclepius Meditech Co., Ltd. during the treatment, with the total use of no less than 6 hours per day, and the other combination treatments will be decided by the investigator depending on the clinical needs; the subjects in the control group will inhale the gas at a flow rate of 2 L/min every day using the reference device of EverFlo Oxygen Concentrator (registration certificate No.: NMPA Registration Standard: 20162542389) developed by Respironics, Inc. US. during the treatment, with the total use of no less than 6 hours per day, and the other combination treatments will be decided by the investigator depending on the clinical needs. During the treatment, the peripheral blood oxygen saturation should be monitored and the oxygen concentration should be increased when necessary (the peripheral oxygen saturation is less than 95% for 30 seconds and other causes have been excluded). Oxygen may be supplied by other devices if the oxygen concentration is sufficient for the subjects in the study group. The oxygen saturation and respiratory rate will be measured at the resting state every day during the treatment, namely after the end of daily treatment and 30 minutes after the inhalation of oxygen and hydrogen/oxygen.

Eligibility criteria: Inclusion Criteria:

All subjects participating in this clinical study must meet all of the following criteria:

1. According to the Diagnosis and Treatment Protocol for COVID-19 (Trial Version 5), under the premise of meeting the diagnostic criteria of moderate COVID-19, the subjects should meet one of the following three conditions:

   ① Respiratory rate (RR): ≥ 20 times/min;

   ② In the state of air absorption and rest, the peripheral oxygen saturation is lower than 95%;

   ③ Arterial partial pressure of oxygen (PaO2)/FiO2: ≤ 400 mmHg (1mmHg=0.133 kPa).
2. ≥18 years old and ≤85 years old subjects with normal autonomous judgment, regardless of gender and region;
3. Subjects voluntarily participate in the study and have signed the informed consent form.

Exclusion Criteria:

1. Have other significant diseases other than COVID-19, that is, a disease that, according to the investigator's judgment, can cause the subject to be at risk due to participation in the study, or affect the study results and the ability of the subject to participate in the study.
2. Women who are pregnant or breastfeeding or plan to be pregnant during the study.
3. Subjects with one of the following respiratory diseases:

   1. Asthma: Based on the investigator's judgment, the subjects are currently diagnosed with asthma.
   2. Subjects with a long-term history of COPD and medication or imaging evidence of significant lung structural damage (e.g., giant pulmonary bullae).

   Other respiratory diseases: Subjects with other active pulmonry diseases, such as active tuberculosis, lung cancer, wet bronchiectasis (the high-resolution CT shows bronchiectasis, with yellow sputum every day), sarcoidosis, idiopathic interstitial pulmonary fibrosis (IPF), primary pulmonary arterial hypertension, and uncontrolled sleep apnea (the severity of the disease will affect the implementation of c)the study according to the investigator's judgment), complicated with pneumothorax, pleural effusion, pulmonary embolism, bronchial asthma, tumor, and fever of unknown origin, etc.

   d)Lung volume reduction: Subjects received lung volume reduction, lobectomy, or bronchoscopic lung volume reduction (endobronchial occlusion, airway bypass, endobronchial valve, steam thermal ablation, biological sealant and airway implant) within 6 months.

   e)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. With other organ failure, ICU monitoring and treatment is needed.

   f)Risk factors for pneumonia: 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.
4. Subjects with serious primary diseases of heart, liver, kidney, hematopoietic system and other important organs or systems.
5. Subjects with mental disorder and cognitive impairment.
6. Subjects who do not follow the study steps.
7. Patients with doubts about the effectiveness of informed consent: Subjects with mental illness, mental retardation, poor motivation, drug abuse (including drugs and alcohol) or other disease history restricting the effectiveness of informed consent in this study.
8. Use of non-expectorants and antioxidants, including large doses of vitamin C and vitamen E.
9. Subjects who are not suitable for participation in this study in the judgment of investigator.

Primary outcomes:
measure: Recovery time
timeFrame: The day from the patient's admission to the Disease Progression to critical type，up to 2 weeks.
Secondary outcomes:
measure: Clinical Symptom Remission time
timeFrame: The day from admission to clinical remission,up to 2 weeks.
measure: fever duration
timeFrame: The day from the patient's body temperature was abnormal to normal,up to 2 weeks.
measure: Leicester cough questionaire (LCQ)
timeFrame: The day from admission to clinical remission,up to 2 weeks.
measure: minimum oxygen
timeFrame: The day from admission to clinical remission,up to 2 weeks.
measure: Negative conversion rate
timeFrame: the first day to the 14th days.
measure: white blood cell(WBC)
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Red blood cells(RBC)
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Hemoglobin(Hb )
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Platelets(PLT)
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Lymphocyte count
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: The percentage of lymphocyte
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: neutrophils
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: C-reactive protein (CRP)
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Myocardial enzyme
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: liver function
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Renal function
timeFrame: The day of admission and clinical remission,up to 2 weeks.
measure: Muscle enzyme
timeFrame: The day of admission and clinical remission,up to 2 weeks.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
References: