Covid19NCT04594460

Hydrogen-oxygen Gas Mixture Inhalation in Patients With Convalescent Coronavirus Disease 2019 (COVID-19)

A study testing Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03 and OLO-1 Medical Molecular Sieve Oxygen Generator in people with Covid19 and Hydrogen-oxygen Gas, run by Guangzhou Institute of Respiratory Disease at 2 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

This study is a multicenter, randomized, open, parallel-controlled study. Qualified subjects will randomly be assigned to the experimental arm or the control arm according to the ratio of 1:1, with age (> 60 years or ≤ 60 years), smoking status (yes/no) and forced expiratory volume in one second/prediction (FEV1 %pred… Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Covid19, Hydrogen-oxygen Gas, AMS-H-03
What is being tested?: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03 and OLO-1 Medical Molecular Sieve Oxygen Generator
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 198 participants
Where: 2 sitesChina
Study dates: 31 Oct 2020to 31 Dec 2021
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

1） Male or female, aged between 18 and 75 (including boundary values) at screening.
2) Severe or critically ill patients who have been diagnosed with a novel coronavirus during hospitalization (COVID-19).
3) After treatment, the patients have met the discharge criteria of "COVID-19 Diagnosis and Treatment Guideline", and the time from hospital discharge is at least 1 month at the time of enrollment. The clinical symptoms of the subjects did not worsen significantly as compared with that at the time of discharge, and the COVID-19 nucleic acid test results are negative for at least 2 consecutive times (one of which could be the nucleic acid test before discharge).
4) Forced vital capacity/per predicted (FVC% pred) ≥ 50%. 5) 50% ≤ FEV1 %pred ≤80%。 6) Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures.
7) Agrees not to participate in other drug/device studies until the study is completed.

Who cannot join

1) With one of the following respiratory diseases:
Subjects with asthma history, or cannot rule out asthma based on the diagnosis of investigator;
Subjects with chronic obstructive pulmonary disease (COPD);
Subjects with following respiratory diseases such as active tuberculosis, lung cancer, sarcoidosis, pulmonary hypertension, pneumothorax, uncontrolled pleural effusion through intervention, pulmonary embolism, etc.;
Lung volume reduction: subjects have had lung volume reduction surgery, pulmonary lobectomy, or bronchoscopic lung volume reduction surgery.
2) Subjects with pulmonary heart disease. 3) Patients who are scheduled for elective surgery during the study period, such as thoracic and abdominal major surgery.

Show all 13Show fewer

4) Subjects, judged by investigators, with previous or current diseases, which may affect the participation in this study or the outcome of this study: such as cancer, diseases of heart, liver, kidney, hematopoietic system and other vital organs or systems, etc.
5) Patients who have undergone surgery within 1 month prior to screening and have not fully recovered.
6) Occurrence of congestive heart failure, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or history of pulmonary embolism within 6 months prior to screening.
7) Patients with active tuberculosis infection within 12 months prior to screening.
8) Pregnancy or lactating women, or women of childbearing potential not agree to either abstinence or use at least one primary form of contraception from the time of screening till the study is completed.
9) Subjects with mental disorders or other conditions that are unable to cooperate effectively with the conduct of the clinical trial.
10) Subjects intolerance to inhalation therapy. 11) Others whom the investigator or sub-investigator judged inappropriate for participation in the study.

Trial locations and contacts

2 sites in 1 country.

Wei-jie Guan, PhD contact

+86-13826042052

battery203@163.com

China2 sites

Guangzhou Institute of Respiratory Disease
Guangzhou, Guangdong, 510120
First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong

Other trials in China

About this study

Official title: A Clinical Trial to Evaluate the Efficacy and Safety of Hydrogen-oxygen Mixed Gas Inhalation in Convalescent Severe/Critically Ill Patients With Novel Coronavirus Pneumonia (COVID-19)

Read the detailed description

Subjects in the experimental arm and the control arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) and oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.), respectively; the treatment duration will not be less than 8 hours per day, for 12 weeks.

Subjects in the experimental arm and the control arm will also receive other medications (excluding antiviral drugs) by the investigator as clinically indicated. Six visits are required for each subject in this study, including Visit 1 (D-7~-1), Visit 2 (D1), Visit 3 (D14±3d), Visit 4 (D28±3d), Visit 5 (D56±7d), Visit 6 (D84±7d).

Conditions: Covid19, Hydrogen-oxygen Gas, AMS-H-03
Being tested: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, OLO-1 Medical Molecular Sieve Oxygen Generator
Keywords: Covid19, Hydrogen-oxygen Gas, AMS-H-03
Medical subject headings: COVID-19

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03Device
the experimental arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) ,the treatment duration will be 8 hours per day, for 12 weeks.
OLO-1 Medical Molecular Sieve Oxygen GeneratorDevice
the control arm will receive oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.)the treatment duration will be 8 hours per day, for 12 weeks.

Study groups in NCT04594460
Study group	Role	What they receive
experimental Group	Experimental	the experimental arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) ,the treatment duration will be 8 hours per day, for 12 weeks. Receives: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03
Control Group	Active comparator	the control arm will receive oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.)the treatment duration will be 8 hours per day, for 12 weeks. Receives: Device: OLO-1 Medical Molecular Sieve Oxygen Generator

What is being measured

The primary outcome is the main question the study is designed to answer.

(VO2max)
The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 12 of treatment.
Measured: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 12 of treatment.

Secondary outcomes (32)

(VO2max)
The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 4 of treatment.
Measured: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 4 of treatment.
(VO2max)
The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 8 of treatment.
Measured: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 8 of treatment.
(VE /VCO2)
Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 4 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 4 of treatment.
(VE /VCO2)
Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 8 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 8 of treatment.
(VE /VCO2)
Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 12 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 12 of treatment.
(VE /VO2)
Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 4 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 4 of treatment.
(VE /VO2)
Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 8 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 8 of treatment.
(VE /VO2)
Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 12 of treatment.
Measured: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 12 of treatment.
(VO2 /HR)
Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 4 treatment.
Measured: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 4 of treatment.
(VO2 /HR)
Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 8 of treatment.
Measured: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 8 of treatment.
(VO2 /HR)
Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 12 of treatment.
Measured: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 12 of treatment.
(P (A-a) O2)
The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 4 of treatment.
Measured: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 4 of treatment.
(P (A-a) O2)
The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 8 of treatment.
Measured: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 8 of treatment.
(P (A-a) O2)
The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 12 of treatment.
Measured: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 12 of treatment.
(P (a-et) CO2)
The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 4 of treatment.
Measured: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 4 of treatment.
(P (a-et) CO2)
The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 8 of treatment.
Measured: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 8 of treatment.
(P (a-et) CO2)
The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 12 of treatment.
Measured: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 12 of treatment.
maximum exercise power
The change from baseline in maximum exercise power at Week 4 of treatment.
Measured: The change from baseline in maximum exercise power at Week 4 of treatment.
maximum exercise power
The change from baseline in maximum exercise power at Week 8 of treatment.
Measured: The change from baseline in maximum exercise power at Week 8 of treatment.
maximum exercise power
The change from baseline in maximum exercise power at Week 12 of treatment.
Measured: The change from baseline in maximum exercise power at Week 12 of treatment.
RER
The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 4 of treatment.
Measured: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 4 of treatment.
RER
The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 8 of treatment.
Measured: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 8 of treatment.
RER
The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 12 of treatment.
Measured: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 12 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 4 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 4 of treatment.
Measured: The change from baseline in total exercise duration at maximum exercise load at Week 4 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 8 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 8 of treatment.
Measured: The change from baseline in total exercise duration at maximum exercise load at Week 8 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 12 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 12 of treatment.
Measured: The change from baseline in total exercise duration at maximum exercise load at Week 12 of treatment.
(SpO2)
The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 4 of treatment.
Measured: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 4 of treatment.
(SpO2)
The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 8 of treatment.
Measured: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 8 of treatment.
(SpO2)
The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 12 of treatment.
Measured: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 12 of treatment.
(mMRC)
The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 4 of treatment.
Measured: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 4 of treatment.
(mMRC)
The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 8 of treatment.
Measured: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 8 of treatment.
(mMRC)
The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 12 of treatment.
Measured: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 12 of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Oct 202031 Dec 2021

First posted20 Oct 2020
Study start31 Oct 2020 (estimated)
Primary completion31 Oct 2021 (estimated)
Study completion31 Dec 2021 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (11)Papers the sponsor has linked to this study.
Other trials for Covid19Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Subjects in the experimental arm and the control arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) and oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.), respectively; the targeted treatment duration will be 8 hours per day, for 12 weeks.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 198 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04594460
Sponsor's protocol ID: AMS-H-03-101
Status last verified: Oct 2020
First submitted: 19 Oct 2020
Last updated: 22 Oct 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Kannan S, Shaik Syed Ali P, Sheeza A, Hemalatha K. COVID-19 (Novel Coronavirus 2019) - recent trends. Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2006-2011. doi: 10.26355/eurrev_202002_20378.
PubMed 32141569
Chinese Clinical Guidance for COVID-19 Penumonia Diagnosis and Treatment (7th edition)
Huang X, Wei F, Hu L, Wen L, Chen K. Epidemiology and Clinical Characteristics of COVID-19. Arch Iran Med. 2020 Apr 1;23(4):268-271. doi: 10.34172/aim.2020.09.
PubMed 32271601
Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, Zhang HY, Sun W, Wang Y. COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020 Jun;92(6):577-583. doi: 10.1002/jmv.25757. Epub 2020 Mar 23.
PubMed 32162702
Li K, Wu J, Wu F, Guo D, Chen L, Fang Z, Li C. The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia. Invest Radiol. 2020 Jun;55(6):327-331. doi: 10.1097/RLI.0000000000000672.
PubMed 32118615
Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, Lei C, Chen R, Zhong N, Li S. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020 Jun 18;55(6):2001217. doi: 10.1183/13993003.01217-2020. Print 2020 Jun.
PubMed 32381497
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.
PubMed 30227423
Yang Y, Zhu Y, Xi X. Anti-inflammatory and antitumor action of hydrogen via reactive oxygen species. Oncol Lett. 2018 Sep;16(3):2771-2776. doi: 10.3892/ol.2018.9023. Epub 2018 Jun 26.
PubMed 30127861
Zhang N, Deng C, Zhang X, Zhang J, Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma Res Pract. 2018 Mar 15;4:3. doi: 10.1186/s40733-018-0040-y. eCollection 2018.
PubMed 29568538
Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X, Shi JD, Lai PZ, Zheng ZG, Zhong NS. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J Thorac Dis. 2020 Jun;12(6):3448-3452. doi: 10.21037/jtd-2020-057. No abstract available.
PubMed 32642277
Ong KC, Ng AW, Lee LS, Kaw G, Kwek SK, Leow MK, Earnest A. Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome. Eur Respir J. 2004 Sep;24(3):436-42. doi: 10.1183/09031936.04.00007104.
PubMed 15358703

Want to know more?

Wei-jie Guan, PhD

+86-13826042052

battery203@163.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 22 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Clinical Trial to Evaluate the Efficacy and Safety of Hydrogen-oxygen Mixed Gas Inhalation in Convalescent Severe/Critically Ill Patients With Novel Coronavirus Pneumonia (COVID-19)
ClinicalTrials.gov ID: NCT04594460
Acronym / sponsor ID: AMS-H-03-101
Conditions: Covid19, Hydrogen-oxygen Gas, AMS-H-03
Keywords: Covid19, Hydrogen-oxygen Gas, AMS-H-03
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 198 participants (estimated)
Lead sponsor: Guangzhou Institute of Respiratory DiseaseUniversity, hospital or other
Study start: 31 Oct 2020 (estimated)
Primary completion: 31 Oct 2021 (estimated)
Study completion: 31 Dec 2021 (estimated)
First posted: 20 Oct 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: Subjects in the experimental arm and the control arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) and oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.), respectively; the targeted treatment duration will be 8 hours per day, for 12 weeks.

Arm	Type	Receives
experimental Group	Experimental	Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03the experimental arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) ,the treatment duration will be 8 hours per day, for 12 weeks.
Control Group	Active comparator	Device: OLO-1 Medical Molecular Sieve Oxygen Generatorthe control arm will receive oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.)the treatment duration will be 8 hours per day, for 12 weeks.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

1） Male or female, aged between 18 and 75 (including boundary values) at screening.
2) Severe or critically ill patients who have been diagnosed with a novel coronavirus during hospitalization (COVID-19).
3) After treatment, the patients have met the discharge criteria of "COVID-19 Diagnosis and Treatment Guideline", and the time from hospital discharge is at least 1 month at the time of enrollment. The clinical symptoms of the subjects did not worsen significantly as compared with that at the time of discharge, and the COVID-19 nucleic acid test results are negative for at least 2 consecutive times (one of which could be the nucleic acid test before discharge).
4) Forced vital capacity/per predicted (FVC% pred) ≥ 50%. 5) 50% ≤ FEV1 %pred ≤80%。 6) Subject (or legally authorized representative) provides written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures.
7) Agrees not to participate in other drug/device studies until the study is completed.

Key exclusion criteria (13 listed)

1) With one of the following respiratory diseases:
2) Subjects with pulmonary heart disease. 3) Patients who are scheduled for elective surgery during the study period, such as thoracic and abdominal major surgery.
4) Subjects, judged by investigators, with previous or current diseases, which may affect the participation in this study or the outcome of this study: such as cancer, diseases of heart, liver, kidney, hematopoietic system and other vital organs or systems, etc.
5) Patients who have undergone surgery within 1 month prior to screening and have not fully recovered.
6) Occurrence of congestive heart failure, uncontrolled or unstable angina or myocardial infarction, cerebrovascular accident, or history of pulmonary embolism within 6 months prior to screening.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03the experimental arm will receive hydrogen-oxygen mixed gas inhalation (Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03, output: 3 L/min (hydrogen concentration: 66.7%, oxygen concentration: 33.3%)) ,the treatment duration will be 8 hours per day, for 12 weeks.	Device	experimental Group
OLO-1 Medical Molecular Sieve Oxygen Generatorthe control arm will receive oxygen inhalation (OLO-1 Medical Molecular Sieve Oxygen Generator, output: 3 L/min (oxygen concentration: 33.3%), Shanghai Ouliang Medical Devices Co., Ltd.)the treatment duration will be 8 hours per day, for 12 weeks.	Device	Control Group

Primary outcome

(VO2max)
Time frame: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 12 of treatment.
The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 12 of treatment.

32 secondary outcomes

(VO2max)
Time frame: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 4 of treatment.
(VO2max)
Time frame: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 8 of treatment.
(VE /VCO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 4 of treatment.
(VE /VCO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 8 of treatment.
(VE /VCO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for carbon dioxide (VE /VCO2) at maximum exercise load at Week 12 of treatment.
(VE /VO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 4 of treatment.
(VE /VO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 8 of treatment.
(VE /VO2)
Time frame: Differences in the change from baseline in ventilatory equivalent for oxygen (VE /VO2) at maximum exercise load at Week 12 of treatment.
(VO2 /HR)
Time frame: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 4 of treatment.
(VO2 /HR)
Time frame: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 8 of treatment.
(VO2 /HR)
Time frame: Differences in the change from baseline in oxygen pulse (VO2 /HR) at maximum exercise load at Week 12 of treatment.
(P (A-a) O2)
Time frame: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 4 of treatment.
(P (A-a) O2)
Time frame: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 8 of treatment.
(P (A-a) O2)
Time frame: The change from baseline in the alveolar-arterial oxygen tension gradient (P (A-a) O2) at maximum exercise load at Week 12 of treatment.
(P (a-et) CO2)
Time frame: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 4 of treatment.
(P (a-et) CO2)
Time frame: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 8 of treatment.
(P (a-et) CO2)
Time frame: The change from baseline in the arterial-to-end-tidal CO2 difference (P (a-et) CO2) at maximum exercise load at Week 12 of treatment.
maximum exercise power
Time frame: The change from baseline in maximum exercise power at Week 4 of treatment.
maximum exercise power
Time frame: The change from baseline in maximum exercise power at Week 8 of treatment.
maximum exercise power
Time frame: The change from baseline in maximum exercise power at Week 12 of treatment.
RER
Time frame: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 4 of treatment.
RER
Time frame: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 8 of treatment.
RER
Time frame: The change from baseline in respiratory quotient (RER) at maximum exercise load at Week 12 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 4 of treatment.
Time frame: The change from baseline in total exercise duration at maximum exercise load at Week 4 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 8 of treatment.
Time frame: The change from baseline in total exercise duration at maximum exercise load at Week 8 of treatment.
The change from baseline in total exercise duration at maximum exercise load at Week 12 of treatment.
Time frame: The change from baseline in total exercise duration at maximum exercise load at Week 12 of treatment.
(SpO2)
Time frame: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 4 of treatment.
(SpO2)
Time frame: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 8 of treatment.
(SpO2)
Time frame: The change from baseline in fingertip oxygen saturation (SpO2) at rest and without oxygen inhalation at Week 12 of treatment.
(mMRC)
Time frame: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 4 of treatment.
(mMRC)
Time frame: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 8 of treatment.
(mMRC)
Time frame: The change from baseline in the modified Medical Research Council (mMRC) Dyspnea Scale score at week 12 of treatment.

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2020.
Background: PubMed 32141569Kannan S, Shaik Syed Ali P, Sheeza A, Hemalatha K. COVID-19 (Novel Coronavirus 2019) - recent trends. Eur Rev Med Pharmacol Sci. 2020 Feb;24(4):2006-2011. doi: 10.26355/eurrev_202002_20378.
BackgroundChinese Clinical Guidance for COVID-19 Penumonia Diagnosis and Treatment (7th edition)
Background: PubMed 32271601Huang X, Wei F, Hu L, Wen L, Chen K. Epidemiology and Clinical Characteristics of COVID-19. Arch Iran Med. 2020 Apr 1;23(4):268-271. doi: 10.34172/aim.2020.09.
Background: PubMed 32162702Li LQ, Huang T, Wang YQ, Wang ZP, Liang Y, Huang TB, Zhang HY, Sun W, Wang Y. COVID-19 patients' clinical characteristics, discharge rate, and fatality rate of meta-analysis. J Med Virol. 2020 Jun;92(6):577-583. doi: 10.1002/jmv.25757. Epub 2020 Mar 23.
Background: PubMed 32118615Li K, Wu J, Wu F, Guo D, Chen L, Fang Z, Li C. The Clinical and Chest CT Features Associated With Severe and Critical COVID-19 Pneumonia. Invest Radiol. 2020 Jun;55(6):327-331. doi: 10.1097/RLI.0000000000000672.
Background: PubMed 32381497Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, Lei C, Chen R, Zhong N, Li S. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020 Jun 18;55(6):2001217. doi: 10.1183/13993003.01217-2020. Print 2020 Jun.
Background: PubMed 30227423Zhou 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.
Background: PubMed 30127861Yang Y, Zhu Y, Xi X. Anti-inflammatory and antitumor action of hydrogen via reactive oxygen species. Oncol Lett. 2018 Sep;16(3):2771-2776. doi: 10.3892/ol.2018.9023. Epub 2018 Jun 26.
Background: PubMed 29568538Zhang N, Deng C, Zhang X, Zhang J, Bai C. Inhalation of hydrogen gas attenuates airway inflammation and oxidative stress in allergic asthmatic mice. Asthma Res Pract. 2018 Mar 15;4:3. doi: 10.1186/s40733-018-0040-y. eCollection 2018.
Background: PubMed 32642277Guan WJ, Wei CH, Chen AL, Sun XC, Guo GY, Zou X, Shi JD, Lai PZ, Zheng ZG, Zhong NS. Hydrogen/oxygen mixed gas inhalation improves disease severity and dyspnea in patients with Coronavirus disease 2019 in a recent multicenter, open-label clinical trial. J Thorac Dis. 2020 Jun;12(6):3448-3452. doi: 10.21037/jtd-2020-057. No abstract available.
Background: PubMed 15358703Ong KC, Ng AW, Lee LS, Kaw G, Kwek SK, Leow MK, Earnest A. Pulmonary function and exercise capacity in survivors of severe acute respiratory syndrome. Eur Respir J. 2004 Sep;24(3):436-42. doi: 10.1183/09031936.04.00007104.
Individual participant dataSharing planned: Undecided

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Wei-jie Guan, PhD contact

+86-13826042052

battery203@163.com

Wei-jie Guan, PhD principal investigator

Guangzhou Institute of Respiratory Disease

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Wei-jie Guan, PhD (+86-13826042052, battery203@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

(VO2max) (time frame: The change from baseline in maximum oxygen consumption (VO2max) at maximum exercise load at Week 12 of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04594460, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2020.