Efficacy and Safety of Hydrogen Inhalation on Bronchiectasis: A Randomized, Multi-center, Double-blind Study

Oxidative Stress Clinical Trial

— HYBRID  

Official title:

Efficacy and Safety of Hydrogen Inhalation on Bronchiectasis (HYBRID): A Randomized, Multi-center, Double-blind, Parallel-group Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02765295
• Other study ID #: GWJ-2015-H2
• Status: Recruiting
• Phase: N/A
• Start date: June 1, 2016
• Est. completion date: December 2021

Study information

• Verified date: July 2019
• Source: Guangzhou Institute of Respiratory Disease
• Contact: Nan-shan Zhong, MD
• Phone: +86-13609003622
• Email: nanshan[@]vip.163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, randomized, double-blind, parallel-group trial. After a 2-week run-in period, eligible patients will be, based on the randomization codes kept in sealed envelopes, randomly assigned to receive usual care (mucolytics and/or chest physiotherapy) plus oxygen inahaltion (1 hr daily for 12 consecutive months) or hydrogen inhalation (1 hr daily for 12 consecutive months) provided by the sponsor. At 3 months after the end-of-treatment, a follow-up visit will be scheduled for all patients.

Description:

This is a multi-center, randomized, double-blind, parallel-group trial. After 2-week run-in period, eligible patients will be, based on the randomization codes kept in sealed envelopes, randomly assigned to two groups.On the basis of usual care [ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily)/ serrapeptase (10mg thrice daily), or carbocisteine (500mg thrice daily) and/or chest physiotherapy (10 min, twice daily)], patients were randomized to receive either hydrogen (66.7%, 3L/min, 1 hr twice daily) inhalation or oxygen inhalation (3L/min, 1 hr twice daily) via nasal canula for 12 months. A follow-up visit at month 3 following end-of-treatment was also scheduled. The primary endpoint was the annual frequency of bronchiectasis exacerbations. Hospital visits were scheduled at baseline and months 1, 3, 6, 9, 12 and 15, respectively. At 3 months after the end-of-treatment, a follow-up visit will be scheduled for all patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Out-patients of either gender, ex- or never-smokers, aged between 18 and 75 years

• Clinically stable bronchiectasis, defined as respiratory symptoms and lung function parameters not exceeding normal daily variations and no acute upper respiratory tract infections for 4 consecutive weeks

• Patients with a history of 2 or more bronchiectasis exacerbations (BEs) within the previous 2 years

Exclusion Criteria:

• Other unstable concomitant systemic illnesses (i.e. coronary heart disease, recent cerebral stroke, severe uncontrolled hypertension, active gastric or duodenal ulcer, uncontrolled diabetes, malignancy, hepatic or renal dysfunction)

• Concomitant asthma, allergic bronchopulmonary aspergillosis, or active tuberculosis

• Concomitant chronic obstructive pulmonary disease as the predominant diagnosis

• Treatment with inhaled, oral or systemic antibiotics within 4 weeks

• Type 2 respiratory failure needing oxygen therapy or non-invasive mechanical ventilation

• Females during lactation or pregnancy

• Poor understanding or failure to properly operate the instrument

• Participation in other clinical trials within 3 months.

Related Conditions & MeSH terms

• Acute Exacerbation of Bronchiectasis
• Bronchiectasis
• Oxidative Stress
• Respiratory Aspiration

Intervention

Device:
• medical ultrasonic hydrogen/oxygen nebulizer (MUNHO)
The medical ultrasonic nebulizers with hydrogen/oxygen generating function (MUNHO) will be provided exclusively by the sponsor, Asclepius Meditec Inc (Shanghai, China). The MUNHO consists of a electrolytic tank which, by using direct current converted from alternating current (220 V), generates the hydrogen and oxygen gas from pure water (2:1 in volume). The MUNHO is also capable of nebulizing the water via ultrasounds with the hydrogen-oxygen mixed gas which is finally delivered to the patient's airways via the facial mask through a plastic tube. Typically, the volume of hydrogen-oxygen mixed gas is 3 liters per minute (3 L/min).
• Medical molecular mesh oxygen generator
medical molecular mesh oxygen generator, type: OLO-1, oxygen flow: 3L/min; Shanghai Ouliang Medical Instrument Inc., Shanghai, China; Registration No.: Shanghai Medical Instrument approval No. 20152540046. This device has an identical appearance as compared with the MUHNO so that the patients could not readily discriminate with the MUHNO, and is also capable of displaying the actual cumulative duration of oxygen inhalation.

Locations

Country	Name	City	State
China	West China Hospital Affiliateyd to Sichuan Universit	Chengdu
China	First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Affiliated Zhongshan Hospital of Fudan University	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Guangzhou Institute of Respiratory Disease

Country where clinical trial is conducted

China, 

References & Publications (36)

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* Note: There are 36 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in airway impedance as measured by impulse oscillometry (Z5, R5, R20, X5, Fres and AX at each visit as compared with baseline	Changes in airway impedance as measured by impulse oscillometry (Z5, R5, R20, X5, Fres and AX at each visit as compared with baseline	baseline, month 1, month 3, month 6, month 9 and month 12
Other	Changes in dyshomogeneity (lung clearance index) at month 6 and 12 as compared with baseline	Changes in dyshomogeneity (lung clearance index) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in anaerobic threshold (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	Changes in anaerobic threshold (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in oxygen pulse (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	Changes in oxygen pulse (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in the difference of arterial and alveolar oxygen partial pressure (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	Changes in the difference of arterial and alveolar oxygen partial pressure (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in carbon dioxide ventilatory equivalent (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	Changes in carbon dioxide ventilatory equivalent (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in 24-hour sputum volume at each visit as compared with baseline	Changes in 24-hour sputum volume at each visit as compared with baseline	baseline, month 1, month 3, month 6, month 9 and month 12
Other	Changes in the levels of sputum inflammatory markers (interleukin-6, interleukin-8 and tumor necrosis factor-a) at month 6 and 12 as compared with baseline	Changes in the levels of sputum inflammatory markers (interleukin-6, interleukin-8 and tumor necrosis factor-a) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Changes in sputum matrix metalloproteinases (MMP-8, MMP-9, MMP-9/TIMP-1 ratio) levels at month 6 and 12 as compared with baseline	Changes in sputum matrix metalloproteinases (MMP-8, MMP-9, MMP-9/TIMP-1 ratio) levels at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	The rates of Pseudomonas aeruginosa isolated from sputum at baseline and end-of-treatment at month 6 and 12 as compared with baseline	The rates of Pseudomonas aeruginosa isolated from sputum at baseline and end-of-treatment at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Other	Sputum microbiota compositions before and after hydrogen therapy	Sputum microbiota compositions before and after hydrogen therapy. This is an exploratory outcome.	up to 12 months (at baseline, month 6, and month 12)
Other	the rate of adverse events	the rate of adverse events	up to 12 months
Primary	Frequency of bronchiectasis exacerbations (BEs) within 12 months	Frequency of bronchiectasis exacerbations (BEs) within 12 months	up to 12 months (1 year)
Secondary	Changes in sputum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline	Changes in sputum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Secondary	Time to the first bronchiectasis exacerbations (BEs) within 12 months	Time to the first bronchiectasis exacerbations (BEs) within 12 months	up to 12 months
Secondary	Changes in sputum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline	Changes in sputum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Secondary	Changes in serum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline	Changes in serum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Secondary	Changes in serum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline	Changes in serum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Secondary	Changes in spirometry, including FEV1, FEV1/FVC ratio and MMEF at each visit following randomization as compared with baseline	Changes in spirometry, including FEV1, FEV1/FVC ratio and MMEF at each visit following randomization as compared with baseline	baseline, month 1, month 3, month 6, month 9 and month 12
Secondary	Changes in CRP levels at month 6 and 12 as compared with baseline	Changes in CRP levels at month 6 and 12 as compared with baseline	baseline, month 6 and month 12
Secondary	Changes in quality of life assessed by using Quality-of-Life Questionnaire--Bronchiectasis (QoL-B) at month 6 and 12 as compared with baseline	Changes in quality of life assessed by using Quality-of-Life Questionnaire--Bronchiectasis (QoL-B) at month 6 and 12 as compared with baseline	baseline, month 6 and month 12