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Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19 (COVID-19)

Primary Purpose

COVID-19

Status
Unknown status
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
oxyhydrogen
Oxygen
Sponsored by
Shanghai Asclepius Meditec Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for COVID-19 focused on measuring Hydrogen-Oxygen Generator with Neburlizer, COVID-19

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • First Affiliated Hospital of Guangzhou Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

oxyhydrogen

oxygen

Arm Description

conventional treatment + hydrogen/ oxygen inhaled

conventional treatment + oxygen inhaled

Outcomes

Primary Outcome Measures

Recovery time
The time from the patient's admission to the Disease Progression to critical type,up to 2 weeks.

Secondary Outcome Measures

Clinical Symptom Remission time
Clinical Symptom Remission was defined as: The patient's body temperature was normal for more than 72 hours (without taking antipyretics or hormones) and had no conscious dyspnea or decreased dyspnea.
fever duration
fever duration is the time during the patient's body temperature was abnormal。
Leicester cough questionaire (LCQ)
The scale consisted of 19 questions in three domains: physical, psychological and social, each with a score ranging from 1.7. Each item represented an adverse event caused by a cough. The answer was scored on a Likert 7 point scale. The higher the score, the better the health condition. The total score ranged from 7 to 21.
minimum oxygen
The minimum oxygen absorption flow with 95% oxygen saturation.
Negative conversion rate
Negative conversion rate of novel coronavirus nucleic acid in respiratory tract specimens 14 days after enrollment.
white blood cell(WBC)
White blood cell (WBC) is a colorless, spherical and nucleated blood cell. The total number of normal adults is (4.0-10.0) x 109 / L, which can be changed in a certain range due to different time of day and the functional state of the body.
Red blood cells(RBC)
also known as red blood cells, are often abbreviated into RBC in Chinese and English in routine tests. They are the most numerous blood cells in the blood, and also the most important medium for transporting oxygen through the blood in vertebrates. At the same time, they also have immune functions.
Hemoglobin(Hb )
The abbreviation of hemoglobin is HGB or Hb. Hemoglobin is a special protein that transports oxygen in red blood cells. It makes the blood red. It is composed of globin and heme. Its globin part is a tetramer composed of two different pairs of globin chains (α chain and β chain).
Platelets(PLT)
Platelets are small pieces of cytoplasm released from the cytoplasm of mature megakaryocytes in bone marrow. Although megakaryocytes are the least in the hematopoietic cells of bone marrow, accounting for only 0.05% of the total number of bone marrow nucleated cells, the platelets produced by megakaryocytes are very important for the hemostatic function of the body.
Lymphocyte count
Lymphocyte count refers to count and calculate the percentage of different types of white blood cells.
The percentage of lymphocyte
Lymphocyte has the function of producing and carrying antibody and preventing virus infection. The percentage of lymphocyte was determined by routine blood test, and the normal value was 20.0% - 40.0%. The percentage of lymphocyte increased mainly in infectious diseases and decreased mainly in immune deficiency diseases.
neutrophils
The membrane of neutrophils can release an unsaturated fatty acid, arachidonic acid. Under the action of enzyme, arachidonic acid can further generate a group of paracrine hormone substances, such as thromboxane and prostaglandin, which play an obvious role in regulating the caliber and permeability of blood vessels, can also cause inflammation and pain, and affect blood coagulation.
C-reactive protein (CRP)
C-reactive protein (CRP) is a kind of protein (acute protein) which rises sharply in the plasma when the body is infected or damaged by tissue. It can activate the complement and strengthen the phagocytosis of phagocytes, so as to play a role in regulating. It can clear away the pathogenic microorganism and the damaged, necrotic and apoptotic tissue cells.
Myocardial enzyme
Myocardial enzyme is a general term for many enzymes existing in the heart, including aspartate aminotransferase (AST), lactate dehydrogenase (LD or LDH), creatine kinase (CK) and isoenzyme, a-hydroxybutyrate dehydrogenase (a-hbd), etc. during acute myocardial infarction, a variety of enzymes in the heart are released due to the necrosis of myocardial cells, so the determination of serum central muscle enzyme is useful for the diagnosis and evaluation of myocardial infarction There is a certain value in the effect of supposition
liver function
The purpose of liver function examination is to detect the liver disease, the degree of liver damage, the cause of liver disease, the prognosis and the cause of jaundice. At present, there are many kinds of clinical trials of liver function, no less than dozens. But each kind of liver function test can only detect a certain function of a certain aspect of the liver, so far, there is still no one test that can reflect all the functions of the liver.
Renal function
Renal function refers to the function of the kidney to excrete the body's metabolic waste, maintain the stability of electrolytes such as sodium, potassium, calcium and acid-base balance. Renal function examination includes blood creatinine, blood urea nitrogen, blood and urine β 2-microglobulin, urinary albumin, urinary immunoglobulin G, urinary secretory immunoglobulin A, etc.
Muscle enzyme
Muscle enzyme generally refers to: phosphocreatine kinase and creatine kinase isoenzyme examination, and some glutamic oxaloacetate transaminase. It is mainly used to check common muscle diseases.

Full Information

First Posted
March 25, 2020
Last Updated
April 3, 2020
Sponsor
Shanghai Asclepius Meditec Inc.
Collaborators
Shanghai Public Health Clinical Center, Henan Provincial People's Hospital, Shenzhen Third People's Hospital, The First People's Hospital of Yunnan, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 6th People's Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT04336462
Brief Title
Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19
Acronym
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 15, 2020 (Actual)
Primary Completion Date
February 21, 2020 (Actual)
Study Completion Date
August 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Asclepius Meditec Inc.
Collaborators
Shanghai Public Health Clinical Center, Henan Provincial People's Hospital, Shenzhen Third People's Hospital, The First People's Hospital of Yunnan, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 6th People's Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Hydrogen-Oxygen Generator with Neburlizer, COVID-19

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
oxyhydrogen
Arm Type
Experimental
Arm Description
conventional treatment + hydrogen/ oxygen inhaled
Arm Title
oxygen
Arm Type
Experimental
Arm Description
conventional treatment + oxygen inhaled
Intervention Type
Device
Intervention Name(s)
oxyhydrogen
Other Intervention Name(s)
Hydrogen/oxygen mixed gas inhaled(proportion 2:1),3 L/min . 6 hour a day.
Intervention Description
Hydrogen-Oxygen Generator with Nebulizer Model: AMS-H-03 Gas production: 2.0 L/min, 2.5 L/min, and 3 L/min, three gears in total (in this study, the gas production of each machine is 3 L/min, two sets are connected and used together by three-way connection, and the total gas production is 6 L/min.) Manufacturer: Shanghai Asclepius Meditech Co., Ltd.
Intervention Type
Device
Intervention Name(s)
Oxygen
Intervention Description
oxygen inhaled,3 L/min . 6 hour a day.
Primary Outcome Measure Information:
Title
Recovery time
Description
The time from the patient's admission to the Disease Progression to critical type,up to 2 weeks.
Time Frame
The day from the patient's admission to the Disease Progression to critical type,up to 2 weeks.
Secondary Outcome Measure Information:
Title
Clinical Symptom Remission time
Description
Clinical Symptom Remission was defined as: The patient's body temperature was normal for more than 72 hours (without taking antipyretics or hormones) and had no conscious dyspnea or decreased dyspnea.
Time Frame
The day from admission to clinical remission,up to 2 weeks.
Title
fever duration
Description
fever duration is the time during the patient's body temperature was abnormal。
Time Frame
The day from the patient's body temperature was abnormal to normal,up to 2 weeks.
Title
Leicester cough questionaire (LCQ)
Description
The scale consisted of 19 questions in three domains: physical, psychological and social, each with a score ranging from 1.7. Each item represented an adverse event caused by a cough. The answer was scored on a Likert 7 point scale. The higher the score, the better the health condition. The total score ranged from 7 to 21.
Time Frame
The day from admission to clinical remission,up to 2 weeks.
Title
minimum oxygen
Description
The minimum oxygen absorption flow with 95% oxygen saturation.
Time Frame
The day from admission to clinical remission,up to 2 weeks.
Title
Negative conversion rate
Description
Negative conversion rate of novel coronavirus nucleic acid in respiratory tract specimens 14 days after enrollment.
Time Frame
the first day to the 14th days.
Title
white blood cell(WBC)
Description
White blood cell (WBC) is a colorless, spherical and nucleated blood cell. The total number of normal adults is (4.0-10.0) x 109 / L, which can be changed in a certain range due to different time of day and the functional state of the body.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Red blood cells(RBC)
Description
also known as red blood cells, are often abbreviated into RBC in Chinese and English in routine tests. They are the most numerous blood cells in the blood, and also the most important medium for transporting oxygen through the blood in vertebrates. At the same time, they also have immune functions.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Hemoglobin(Hb )
Description
The abbreviation of hemoglobin is HGB or Hb. Hemoglobin is a special protein that transports oxygen in red blood cells. It makes the blood red. It is composed of globin and heme. Its globin part is a tetramer composed of two different pairs of globin chains (α chain and β chain).
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Platelets(PLT)
Description
Platelets are small pieces of cytoplasm released from the cytoplasm of mature megakaryocytes in bone marrow. Although megakaryocytes are the least in the hematopoietic cells of bone marrow, accounting for only 0.05% of the total number of bone marrow nucleated cells, the platelets produced by megakaryocytes are very important for the hemostatic function of the body.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Lymphocyte count
Description
Lymphocyte count refers to count and calculate the percentage of different types of white blood cells.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
The percentage of lymphocyte
Description
Lymphocyte has the function of producing and carrying antibody and preventing virus infection. The percentage of lymphocyte was determined by routine blood test, and the normal value was 20.0% - 40.0%. The percentage of lymphocyte increased mainly in infectious diseases and decreased mainly in immune deficiency diseases.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
neutrophils
Description
The membrane of neutrophils can release an unsaturated fatty acid, arachidonic acid. Under the action of enzyme, arachidonic acid can further generate a group of paracrine hormone substances, such as thromboxane and prostaglandin, which play an obvious role in regulating the caliber and permeability of blood vessels, can also cause inflammation and pain, and affect blood coagulation.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
C-reactive protein (CRP)
Description
C-reactive protein (CRP) is a kind of protein (acute protein) which rises sharply in the plasma when the body is infected or damaged by tissue. It can activate the complement and strengthen the phagocytosis of phagocytes, so as to play a role in regulating. It can clear away the pathogenic microorganism and the damaged, necrotic and apoptotic tissue cells.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Myocardial enzyme
Description
Myocardial enzyme is a general term for many enzymes existing in the heart, including aspartate aminotransferase (AST), lactate dehydrogenase (LD or LDH), creatine kinase (CK) and isoenzyme, a-hydroxybutyrate dehydrogenase (a-hbd), etc. during acute myocardial infarction, a variety of enzymes in the heart are released due to the necrosis of myocardial cells, so the determination of serum central muscle enzyme is useful for the diagnosis and evaluation of myocardial infarction There is a certain value in the effect of supposition
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
liver function
Description
The purpose of liver function examination is to detect the liver disease, the degree of liver damage, the cause of liver disease, the prognosis and the cause of jaundice. At present, there are many kinds of clinical trials of liver function, no less than dozens. But each kind of liver function test can only detect a certain function of a certain aspect of the liver, so far, there is still no one test that can reflect all the functions of the liver.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Renal function
Description
Renal function refers to the function of the kidney to excrete the body's metabolic waste, maintain the stability of electrolytes such as sodium, potassium, calcium and acid-base balance. Renal function examination includes blood creatinine, blood urea nitrogen, blood and urine β 2-microglobulin, urinary albumin, urinary immunoglobulin G, urinary secretory immunoglobulin A, etc.
Time Frame
The day of admission and clinical remission,up to 2 weeks.
Title
Muscle enzyme
Description
Muscle enzyme generally refers to: phosphocreatine kinase and creatine kinase isoenzyme examination, and some glutamic oxaloacetate transaminase. It is mainly used to check common muscle diseases.
Time Frame
The day of admission and clinical remission,up to 2 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All subjects participating in this clinical study must meet all of the following criteria: 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). ≥18 years old and ≤85 years old subjects with normal autonomous judgment, regardless of gender and region; Subjects voluntarily participate in the study and have signed the informed consent form. Exclusion Criteria: 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. Women who are pregnant or breastfeeding or plan to be pregnant during the study. Subjects with one of the following respiratory diseases: Asthma: Based on the investigator's judgment, the subjects are currently diagnosed with asthma. 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. Subjects with serious primary diseases of heart, liver, kidney, hematopoietic system and other important organs or systems. Subjects with mental disorder and cognitive impairment. Subjects who do not follow the study steps. 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. Use of non-expectorants and antioxidants, including large doses of vitamin C and vitamen E. Subjects who are not suitable for participation in this study in the judgment of investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zhang Ze Guang, doctor
Phone
18928868242
Email
zheng862080@139.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xin Yong Lin, master
Phone
13901754567
Email
ceo@ascleway.com
Facility Information:
Facility Name
First Affiliated Hospital of Guangzhou Medical University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zheng Z Guang, doctor
Phone
86-20-83062843
Email
zheng862080@139.com
First Name & Middle Initial & Last Name & Degree
Hu J Ying, master
Phone
13544425867
Email
hujieyingjy@126.com

12. IPD Sharing Statement

Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/30227423
Description
Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis

Learn more about this trial

Hydrogen-Oxygen Generator With Nebulizer in the Improvement of Symptoms in Patients Infected With COVID-19

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