Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of COVID-19 Positive Patients

A Prospective, Multi-center, Randomized, Controlled Clinical Trial to Evaluate the Effectiveness and Safety of Hydrogen-Oxygen Generator With Nebulizer for Adjuvant Treatment of 2019 Novel Coronavirus Pneumonia (COVID-19) Positive Patients

This is a prospective, multicenter, randomized, controlled, superiority clinical trial. It is expected that the test group would have better effectiveness than the control group in the primary evaluation indicator (time to negative viral nucleic acid detection from the start of study treatment). The test group will use the investigational medical device Hydrogen-Oxygen Generator with Nebulizer (Shanghai Asclepius Meditec Co., Ltd.) + basic treatment (the investigator provides corresponding symptomatic support treatment based on the condition of the patients), and the control group will use the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen) + basic treatment, to evaluate the effectiveness and safety of the investigational medical device Hydrogen-Oxygen Generator with Nebulizer for adjuvant treatment of COVID-19 patients.

Study Overview

• Status: Active, not recruiting
• Conditions: Covid19; Hydrogen-oxygen Gas; AMS-H-03
• Intervention / Treatment: Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen)

Detailed Description

A total of 188 subjects who met the requirements of this study will be randomized into the test group or the control group in a 1:1 ratio to receive treatment, and the subjects will be observed and evaluated in the period from treatment after enrollment to discharge.

All enrolled subjects will receive treatment and visit, including screening visit (within 3 days before enrollment), randomization and treatment visit (Day 0), 1, 2, 3, 5, 7, 10, and discharge visit after treatment.

The primary effectiveness evaluation indicator (time to negative viral nucleic acid detection from the start of the study treatment), the secondary effectiveness evaluation indicators (viral nucleic acid negative conversion rate, imaging evaluation, inflammatory indicators such as CRP, IL-6, lymphocytes, clinical response rate at 7 days of treatment, recovery rate and recovery time of major symptoms, index oxygen saturation, and Ct value of nucleic acid detection), and safety evaluation indicators ( incidence of AE and SAE, incidence of device deficiencies) of the two groups will be collected and analyzed.

• Study Type: Interventional
• Enrollment (Anticipated): 188
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital, Medical School of Shanghai Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female subjects aged between 18 and 80 years old (inclusive).
• Diagnosed as general type of COVID-19 according to the criteria of Scheme for Diagnosis and Treatment of 2019 Novel Coronavirus Pneumonia (Trial Version 9).
• Subjects who are willing to participate and provided written informed consent form.

Exclusion Criteria:

• Diagnosed as mild, severe, critical or asymptomatic type of COVID-19.
• Subjects in the treatment or active stage of malignant tumor.
• Subjects who are intolerable to inhalation treatment.
• Subjects with mental disorders or cognitive impairment who are unable to provide consent.
• Subjects with any immunodeficiency requiring chronic treatment with any corticosteroid or other immunosuppressants.
• Complicate serious primary diseases such as heart, liver, kidney, and hematopoietic diseases; acute exacerbation phase of chronic obstructive pulmonary disease, or acute attack of bronchial asthma.
• Subjects who are using any non-expectorant antioxidant drug, including large doses of vitamin C and vitamin E.
• Subjects who are participating any other clinical study of any investigational drug or medical device.
• Pregnant or lactating women.
• Any other condition judged as inappropriate to participate in this study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: experimental Group; The test group will use the investigational medical device Hydrogen-Oxygen Generator with Nebulizer (Shanghai Asclepius Meditec Co., Ltd.) + basic treatment (the investigator provides corresponding symptomatic support treatment based on the condition of the patients)	Device: Hydrogen-Oxygen Generator with Nebulizer, AMS-H-03; The experimental group used the experimental medical device Hydrogen-Oxygen Generator with Nebulizer(Shanghai Asclepius Meditec Co., Ltd. ) The flow rate was 3L/min, and the cumulative treatment time was not less than 6 hours per day.
ACTIVE_COMPARATOR: Control Group; The control group will use the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen) + basic treatment	Device: the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen); the hospital routine oxygen supply equipment (wall oxygen or cylinder oxygen). The flow rate was 3L/min, and the cumulative treatment time was not less than 6 hours per day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to negative viral nucleic acid detection from the start of the study treatment.	Time to negative viral nucleic acid detection is defined as two consecutive negative viral nucleic acid detections of respiratory specimens (samples will be taken at least 24 hours apart).	through study completion, The average time from enrollment to two consecutive negative nucleic acid tests of respiratory specimens (sampling time interval of at least 24 hours) was approximately 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Negative rate based on viral nucleic acid detection	Negative viral nucleic acid detection is defined as two consecutive negative nucleic acid detections of respiratory specimens (the sampling time interval will be at least 24 hours).	The negative rate of viral nucleic acid detection from 3, 5, 7, 10 days after the treatment to discharge will be analyzed.
Imaging evalution indicators	Significant lesion absorption >50%, lesion absorption degree of 10%-50%, lesion absorption degree of < 10%, and lesion progression compared with that at enrollment as showed in lung imaging.	Lung imaging changes were analyzed on the 3rd and 7th day after treatment.
CRP	Inflammatory indicators such as CRP	The changes were compared with those on day 3, 5 and 7 before treatment.
Clinical effectiveness within 7 days	Clinically effective is defined as "cured" + "significant effective" + "effective". Clinical response rate = (total number of patients of "cured" + "significant effective" + "effective")/total number of subjects included in the analysis ×100%. It should be noted that in the actual situation, some clinical symptoms or signs may still be observed in the follow up after the end of treatment. If it is indicated that the above situation is resulted from the underlying disease, the investigator can also consider the patient to be clinically cured after comprehensive judgment based on the clinical data.	The clinical effective rate after 7 days of treatment will be used as the evaluation indiactor
recovery rate and time to recovery of main symptoms	It is defined as all major symptoms (fever, fatigue, cough, expectoration, chest tightness, chest pain, shortness of breath, and dyspnea) at enrollment had all disappeared or completely returned to normal at follow up.	The patients will be followed up at 3, 5, 7, 10 days after the treatment and at discharge visit.
Oxygen saturation	Oxygen saturation	This will be evaluated at 3, 5, 7, and 10 days after the treatment and at discharge. The oxygen saturation will be measured at rest after stopping oxygen or hydrogen inhalation for 10 minutes.
Ct value in nucleic acid detection	Ct value in nucleic acid detection	This will be evaluated at1,2，3, 5, 7, and 10 days after the treatment and at discharge.
IL-6	Inflammatory indicators such as IL-6	The changes were compared with those on day 3, 5 and 7 before treatment.
lymphocytes	Inflammatory indicators such as lymphocytes	The changes were compared with those on day 3, 5 and 7 before treatment.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE/SAE percentage	AE/SAE percentage	through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Helpful Links

• WHO. Summary of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003. Dec 31, 2003.
• WHO. Middle East respiratory syndrome coronavirus (MERS-CoV). November, 2019.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 16, 2022
• Primary Completion (ANTICIPATED): December 30, 2022
• Study Completion (ANTICIPATED): December 30, 2022

Study Registration Dates

• First Submitted: August 14, 2022
• First Submitted That Met QC Criteria: September 13, 2022
• First Posted (ACTUAL): September 14, 2022

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: Covid19; Hydrogen-oxygen Gas; AMS-H-03
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: AMS-H-03-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No