Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)

Covid19 Clinical Trial

Official title:

A Multi-center, Randomized, Parallel Controlled, Double-Blinded Clinical Trial to Evaluate the Effectiveness and Safety of Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of Novel Coronavirus Disease 2019 (COVID-19)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05770206
• Other study ID #: AMS-H-03-105
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 1, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: March 2023
• Source: Guangzhou Institute of Respiratory Disease
• Contact: Guan Wei-jie, PhD
• Phone: +86-13826042052
• Email: battery203[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, randomized, parallel controlled, double-blinded clinical trial to evaluate the effectiveness and safety of Hydrogen-Oxygen Generator with Nebulizer for adjuvant treatment of COVID-19 patients. The test group is expected to be superior to the control group in the primary endpoint (percentage of subjects achieving clinical recovery at Day 7 of study treatment). Subjects in the test group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects); and subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group).

Description:

Data of the following effectiveness and safety endpoints of subjects in the two groups will be collected and analyzed in this study, including of the primary effectiveness endpoint: percentage of subjects achieving clinical recovery at Day 7 of study treatment; and the secondary effectiveness endpoints: percentage of subjects achieving clinical recovery on Day 2, 3, 5, 10 of study treatment and that before discharge; percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more on Day 2, 3, 5, 7, 10 of study treatment and before discharge; reduction of WHO Clinical Progression Scale score on Day 2, 3, 5, 7, 10 of study treatment and before discharge; changes in COVID-19 symptom scores on Day 2, 3, 5, 7, 10 of study treatment and before discharge; total length of hospital stay; time from randomization to conversion to general COVID-19; time from randomization to conversion to mild COVID-19 disease; percentage of patients with no fever, shortness of breath and chest pain on Day 2, 3, 5, 7, 10 of study treatment and before discharge; Oxygen saturation based on finger blood samples in resting non-oxygen inhalation state; and safety evaluation variables including incidences of AEs, SAEs and device deficiencies.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 218
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Male or female subjects aged between 18 and 75 years old (inclusive).

2. Diagnosed with mild, moderate or severe type of COVID-19 according to the criteria of Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (Trial Version 10).

3. Positive result for COVID-19 nucleic acid test or rapid antigen detection at screening visit;

4. Presenting with at least one respiratory symptom (e.g. dyspnoea, shortness of breath) at hospital admission.

5. Be willing to participate in this trial and provide written informed consent form.

Exclusion Criteria:

1. Subjects with critical or asymptomatic type of COVID-19;

2. Subjects with any known malignant tumor or life expectancy less than half a year.

3. Subjects who are intolerable to inhalation treatment.

4. Subjects with mental disorders or cognitive impairment who are unable to provide consent.

5. Subjects with any immunodeficiency requiring chronic treatment with any corticosteroid or other immunosuppressants.

6. Complicate with any serious cardiac, hepatic or renal disease (as indicated by aspartate aminotransferase [AST] and alanine aminotransferase [ALT] = 2 × upper limit of normal [ULN], or creatinine = 176.8mmol/L, or New York Heart Association (NYHA) Classification for heart failure of Class IV) or any serious primary systematic disease.

7. Subjects who are going to use any non-expectorant antioxidant drug, including large doses of vitamin C and vitamin E during the study period.

8. Subjects who are participating in any other clinical study on any investigational drug or medical device.

9. Pregnant or lactating women.

10. Subjects with any other condition judged as inappropriate to participate in this study by the investigator.

Related Conditions & MeSH terms

• AMS-H-03
• COVID-19
• Covid19
• Hydrogen-oxygen Gas

Intervention

Device:
• Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03
Subjects in the experimental group will receive treatment by using Hydrogen-Oxygen Generator with Nebulizer (manufactured by Shanghai Asclepius Meditec Co., Ltd., flow rate: 3L/min) combined with conventional basic supportive treatment (symptomatic support treatment determined by the investigator based on the condition of the subjects);
• OLO-1 Medical Molecular Sieve Oxygen Generator
subjects in the control group will receive treatment by using Medical Molecular Sieve Oxygen Generator (manufactured by Shanghai Ouliang Medical Devices Co., Ltd., flow rate: 3L/min, provided by the sponsor) combined with conventional basic supportive treatment (same with that in the test group).

Locations

Country	Name	City	State
China	First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease

Country where clinical trial is conducted

China, 

References & Publications (8)

de Groot RJ, Baker SC, Baric RS, Brown CS, Drosten C, Enjuanes L, Fouchier RA, Galiano M, Gorbalenya AE, Memish ZA, Perlman S, Poon LL, Snijder EJ, Stephens GM, Woo PC, Zaki AM, Zambon M, Ziebuhr J. Middle East respiratory syndrome coronavirus (MERS-CoV): announcement of the Coronavirus Study Group. J Virol. 2013 Jul;87(14):7790-2. doi: 10.1128/JVI.01244-13. Epub 2013 May 15. No abstract available. — View Citation

Drosten C, Gunther S, Preiser W, van der Werf S, Brodt HR, Becker S, Rabenau H, Panning M, Kolesnikova L, Fouchier RA, Berger A, Burguiere AM, Cinatl J, Eickmann M, Escriou N, Grywna K, Kramme S, Manuguerra JC, Muller S, Rickerts V, Sturmer M, Vieth S, Klenk HD, Osterhaus AD, Schmitz H, Doerr HW. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1967-76. doi: 10.1056/NEJMoa030747. Epub 2003 Apr 10. — View Citation

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. Erratum In: J Thorac Dis. 2020 Aug;12(8):4591-4592. — View Citation

Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T, Emery S, Tong S, Urbani C, Comer JA, Lim W, Rollin PE, Dowell SF, Ling AE, Humphrey CD, Shieh WJ, Guarner J, Paddock CD, Rota P, Fields B, DeRisi J, Yang JY, Cox N, Hughes JM, LeDuc JW, Bellini WJ, Anderson LJ; SARS Working Group. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003 May 15;348(20):1953-66. doi: 10.1056/NEJMoa030781. Epub 2003 Apr 10. — View Citation

Kuiken T, Fouchier RA, Schutten M, Rimmelzwaan GF, van Amerongen G, van Riel D, Laman JD, de Jong T, van Doornum G, Lim W, Ling AE, Chan PK, Tam JS, Zambon MC, Gopal R, Drosten C, van der Werf S, Escriou N, Manuguerra JC, Stohr K, Peiris JS, Osterhaus AD. Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome. Lancet. 2003 Jul 26;362(9380):263-70. doi: 10.1016/S0140-6736(03)13967-0. — View Citation

Zaki AM, van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med. 2012 Nov 8;367(19):1814-20. doi: 10.1056/NEJMoa1211721. Epub 2012 Oct 17. Erratum In: N Engl J Med. 2013 Jul 25;369(4):394. — View Citation

Zheng ZG, Sun WZ, Hu JY, Jie ZJ, Xu JF, Cao J, Song YL, Wang CH, Wang J, Zhao H, Guo ZL, Zhong NS. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respir Res. 2021 May 13;22(1):149. doi: 10.1186/s12931-021-01740-w. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of AEs/SAEs	Definition: An AE is defined as any untoward medical occurrence during the course of the clinical trial, whether or not related to the study device. For the definition of SAE	through study completion, an average of 14 days
Other	Incidence of Device Deficiency	Definition: a device deficiency is defined as any inadequacy of a medical device which may pose inappropriate risks to the health or safety of the subjects under normal use of the device during the clinical trial, including inadequate labelling, quality issue, and malfunctions, etc.	through study completion, an average of 14 days
Primary	the percentage of subjects with clinical recovery on Day 7 of study treatment.	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	Day 7of study treatment
Secondary	Percentage of subjects achieving clinical recovery	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	Day 2of study treatment
Secondary	Percentage of subjects achieving clinical recovery	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	Day 3 of study treatment
Secondary	Percentage of subjects achieving clinical recovery	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	Day 5of study treatment
Secondary	Percentage of subjects achieving clinical recovery	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	Day 10 of study treatment
Secondary	Percentage of subjects achieving clinical recovery	continuous clinical recovery is defined as score (see Appendix 2) of COVID-19 related symptoms = 1 continued for 2 consecutive days or discharge criteria is met. Time of continuous clinical recovery is defined as time (days) between the first initiation of the study treatment devices and the time when the score of relevant COVID-19 related symptoms = 1 continues for 2 consecutive days or discharge criteria is met (whichever comes first).	through study completion, an average of 10 days
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Day 2 of study treatment
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Day 3 of study treatment
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Day 5 of study treatment
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Day 7 of study treatment
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Day 10 of study treatment
Secondary	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	Percentage of subjects whose WHO Clinical Progression Scale score decreased by 1 point or more	The period from the beginning of treatment in patients enrolled to the time before discharge
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	Day 2 of study treatment
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	Day 3 of study treatment
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	Day 5 of study treatment
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	Day 7 of study treatment
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	Day 10 of study treatment
Secondary	Point reduction of WHO Clinical Progression Scale score	Point reduction of WHO Clinical Progression Scale score	The period from the beginning of treatment in patients enrolled to the time before discharge
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	Day 2 of the study treatment
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	Day 3 of the study treatment
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	Day 5 of the study treatment
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	Day 7 of the study treatment
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	Day 10 of the study treatment
Secondary	Changes in scores of COVID-19 related symptoms	Changes in scores of COVID-19 related symptoms	The period from the beginning of treatment in patients enrolled to the time before discharge
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Day 2 of the study treatment
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Day 3 of the study treatment
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Day 5 of the study treatment
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Day 7 of the study treatment
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Day 10 of the study treatment
Secondary	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	Percentage of subjects whose COVID-19 related symptoms have recovered to normal	through study completion, an average of 10 days
Secondary	Total length of hospital stay	Total length of hospital stay	through study completion, an average of 14 days
Secondary	Time from randomization to conversion to mild type of COVID-19	Time from randomization to conversion to mild type of COVID-19	Time from randomization to conversion to mild type of COVID-19
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	Day 2 of study treatment
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	Day 3 of study treatment
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	Day 5 of study treatment
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	Day 7 of study treatment
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	Day 10 of study treatment
Secondary	Oxygen saturation in resting non-oxygen inhalation state	Oxygen saturation will be measured based on finger blood samples in resting state at 10 minutes after stopping the use of the study device for subjects in the test group and the control group	through study completion, an average of 10 days
Secondary	CRP	C-reactive protein	Day 3 of study treatment
Secondary	CRP	C-reactive protein	Day 7 of study treatment
Secondary	CRP	C-reactive protein	Day 10 of study treatment
Secondary	CRP	C-reactive protein	through study completion, an average of 10 days
Secondary	IL-6	IL-6	Day 3 of study treatment
Secondary	IL-6	IL-6	Day 7 of study treatment
Secondary	IL-6	IL-6	Day 10 of study treatment
Secondary	IL-6	IL-6	through study completion, an average of 10 days
Secondary	ferritin	ferritin	Day 3 of study treatment
Secondary	ferritin	ferritin	Day 7 of study treatment
Secondary	ferritin	ferritin	Day 10 of study treatment
Secondary	ferritin	ferritin	through study completion, an average of 10 days
Secondary	lymphocytes	lymphocytes	Day 3 of study treatment
Secondary	lymphocytes	lymphocytes	Day 7of study treatment
Secondary	lymphocytes	lymphocytes	Day 10 of study treatment
Secondary	lymphocytes	lymphocytes	through study completion, an average of 10 days
Secondary	neutrophil to lymphocyte ratio	neutrophil to lymphocyte ratio	Day 3 of study treatment
Secondary	neutrophil to lymphocyte ratio	neutrophil to lymphocyte ratio	Day 7 of study treatment
Secondary	neutrophil to lymphocyte ratio	neutrophil to lymphocyte ratio	Day 10 of study treatment
Secondary	neutrophil to lymphocyte ratio	neutrophil to lymphocyte ratio	through study completion, an average of 10 days
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Day 2 of study treatment
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Day 3 of study treatment
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Day 5 of study treatment
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Day 7 of study treatment
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Day 10 of study treatment
Secondary	Percentage of patients with fever, shortness of breath and chest pain all disappeared	Percentage of patients with fever, shortness of breath and chest pain all disappeared	through study completion, an average of 10 days