Clinical trial NCT04378712: Hydrogen/Oxygen Mixed Gas Inhalation for Coronavirus Disease 2019 (COVID-19)
Official title: Effects of Hydrogen/Oxygen Mixed Gas Inhalation for Patients With Coronavirus Disease 2019 (COVID-19) Who Had Dyspnea: A Multicenter, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid-19
Hydrogen/Oxygen Mixed Gas
Dyspnea
Keywords: Covid-19
Hydrogen/oxygen mixed gas
Dyspnea
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2020-05-07
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of patients with improved disease severity at day 2
timeFrame: from baseline to day 2
measure: The proportion of patients with improved disease severity at day 3
timeFrame: from baseline to day 3
measure: The proportion of patients with improved disease severity at the day before hospital discharge
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
Secondary outcomes:
measure: The change from baseline in oxygen saturation at day 2.
timeFrame: from baseline to day 2
measure: The change from baseline in oxygen saturation at day 3.
timeFrame: from baseline to day 3
measure: The change from baseline in oxygen saturation at the day before hospital discharge
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
measure: The change from baseline in dyspnea scale at day 2.
timeFrame: from baseline to day 2
measure: The change from baseline in dyspnea scale at day 3.
timeFrame: from baseline to day 3
measure: The change from baseline in dyspnea scale at the day before hospital discharge.
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
measure: The change from baseline in cough scale at day 2
timeFrame: from baseline to day 2
measure: The change from baseline in cough scale at day 3
timeFrame: from baseline to day 3
measure: The change from baseline in cough scale at the day before hospital discharge
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
measure: The change from baseline in chest pain scale at day 2.
timeFrame: from baseline to day 2
measure: The change from baseline in chest pain scale at day 3.
timeFrame: from baseline to day 3
measure: The change from baseline in chest pain scale at the day before hospital discharge.
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
measure: The change from baseline in chest distress scale at day 2.
timeFrame: from baseline to day 2
measure: The change from baseline in chest distress scale at day 3.
timeFrame: from baseline to day 3
measure: The change from baseline in chest distress scale at the day before hospital discharge.
timeFrame: up to 14 days (from baseline to the day before hospital discharge)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Guangzhou Institute of Respiratory Disease
name: Wei-jie Guan, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, Huang H, Zhang L, Zhou X, Du C, Zhang Y, Song J, Wang S, Chao Y, Yang Z, Xu J, Zhou X, Chen D, Xiong W, Xu L, Zhou F, Jiang J, Bai C, Zheng J, Song Y. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. doi: 10.1001/jamainternmed.2020.0994.
citation: Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, Liu S, Zhao P, Liu H, Zhu L, Tai Y, Bai C, Gao T, Song J, Xia P, Dong J, Zhao J, Wang FS. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020 Apr;8(4):420-422. doi: 10.1016/S2213-2600(20)30076-X. Epub 2020 Feb 18. No abstract available.
citation: Zhou ZQ, Zhong CH, Su ZQ, Li XY, Chen Y, Chen XB, Tang CL, Zhou LQ, Li SY. Breathing Hydrogen-Oxygen Mixture Decreases Inspiratory Effort in Patients with Tracheal Stenosis. Respiration. 2019;97(1):42-51. doi: 10.1159/000492031. Epub 2018 Sep 18.
citation: Morgan SE, Vukin K, Mosakowski S, Solano P, Stanton L, Lester L, Lavani R, Hall JB, Tung A. Use of heliox delivered via high-flow nasal cannula to treat an infant with coronavirus-related respiratory infection and severe acute air-flow obstruction. Respir Care. 2014 Nov;59(11):e166-70. doi: 10.4187/respcare.02728. Epub 2014 Aug 12.
citation: Kneyber MC, van Heerde M, Markhorst DG, Plotz FB. Mechanical ventilation with heliox decreases respiratory system resistance and facilitates CO2 removal in obstructive airway disease. Intensive Care Med. 2006 Oct;32(10):1676-7. doi: 10.1007/s00134-006-0348-6. Epub 2006 Aug 23. No abstract available.