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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention Group | Experimental | H2-O2 (66% hydrogen; 33% oxygen) inhalation. 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. |
|
| Control Group | Other | Usual care referred to the standard-of-care (including oxygen therapy) recommended by Chinese National Health Commission. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hydrogen Oxygen Generator with Nebulizer | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| The proportion of patients with improved disease severity at day 2 | The proportion of patients with improved disease severity (by at least one scale) at day 2 | from baseline to day 2 |
| The proportion of patients with improved disease severity at day 3 | The proportion of patients with improved disease severity (by at least one scale) at day 3 | from baseline to day 3 |
| The proportion of patients with improved disease severity at the day before hospital discharge | The proportion of patients with improved disease severity (by at least one scale) at the day before hospital discharge | up to 14 days (from baseline to the day before hospital discharge) |
| Measure | Description | Time Frame |
|---|---|---|
| The change from baseline in oxygen saturation at day 2. | The change from baseline in oxygen saturation at day 2. | from baseline to day 2 |
| The change from baseline in oxygen saturation at day 3. |
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Inclusion Criteria:
Exclusion Criteria:
Women who are pregnant or breastfeeding or plan to be pregnant during the study.
Subjects with one of the following respiratory diseases:
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| Name | Affiliation | Role |
|---|---|---|
| Wei-jie Guan, PhD | Guangzhou Institute of Respiratory Disease | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First Affiliated Hospital of Guangzhou Medical University | Guangzhou | Guangdong | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32167524 | Background | 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. | |
| 32085846 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D004417 | Dyspnea |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D009330 | Nebulizers and Vaporizers |
| D059039 | Standard of Care |
| ID | Term |
|---|---|
| D004864 | Equipment and Supplies |
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
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| Standard-of-care | Other | Standard-of-care consisted of the supportive therapies (including oxygen therapy) recommended by the Chinese National Health Commission |
|
The change from baseline in oxygen saturation at day 3.
| from baseline to day 3 |
| The change from baseline in oxygen saturation at the day before hospital discharge | The change from baseline in oxygen saturation at the day before hospital discharge. | up to 14 days (from baseline to the day before hospital discharge) |
| The change from baseline in dyspnea scale at day 2. | The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 |
| The change from baseline in dyspnea scale at day 3. | The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 |
| The change from baseline in dyspnea scale at the day before hospital discharge. | The change from baseline in dyspnea scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge. | up to 14 days (from baseline to the day before hospital discharge) |
| The change from baseline in cough scale at day 2 | The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2 | from baseline to day 2 |
| The change from baseline in cough scale at day 3 | The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3 | from baseline to day 3 |
| The change from baseline in cough scale at the day before hospital discharge | The change from baseline in cough scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge | up to 14 days (from baseline to the day before hospital discharge) |
| The change from baseline in chest pain scale at day 2. | The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 |
| The change from baseline in chest pain scale at day 3. | The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 |
| The change from baseline in chest pain scale at the day before hospital discharge. | The change from baseline in chest pain scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge. | up to 14 days (from baseline to the day before hospital discharge) |
| The change from baseline in chest distress scale at day 2. | The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 2. | from baseline to day 2 |
| The change from baseline in chest distress scale at day 3. | The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at day 3. | from baseline to day 3 |
| The change from baseline in chest distress scale at the day before hospital discharge. | The change from baseline in chest distress scale (ranging from 0-4, with higher scores indicating severer outcomes) at the day before hospital discharge. | up to 14 days (from baseline to the day before hospital discharge) |
| Background |
| 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. |
| 30227423 | Background | 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. |
| 25118308 | Background | 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. |
| 16927073 | Background | 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. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D017530 | Health Care Quality, Access, and Evaluation |