Acute Exacerbation of Bronchiectasis, Bronchiectasis, Oxidative Stress
Conditions
Keywords
Hydrogen, Inhalation, bronchiectasis
Brief 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.
Detailed 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.
Interventions
DEVICEmedical 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).
DEVICEMedical 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.
Sponsors
Guangzhou Institute of Respiratory Disease
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of bronchiectasis exacerbations (BEs) within 12 months | up to 12 months (1 year) | Frequency of bronchiectasis exacerbations (BEs) within 12 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to the first bronchiectasis exacerbations (BEs) within 12 months | up to 12 months | Time to the first bronchiectasis exacerbations (BEs) within 12 months |
| 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 | Changes in sputum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) 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 | Changes in serum 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 | Changes in sputum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 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 | Changes in spirometry, including FEV1, FEV1/FVC ratio and MMEF at each visit following randomization as compared with baseline |
| Changes in CRP levels at month 6 and 12 as compared with baseline | baseline, month 6 and month 12 | Changes in CRP levels 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 | 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 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 | Changes in serum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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 | The rates of Pseudomonas aeruginosa isolated from sputum at baseline and end-of-treatment at month 6 and 12 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 | Changes in airway impedance as measured by impulse oscillometry (Z5, R5, R20, X5, Fres and AX at each visit as compared with baseline |
| the rate of adverse events | up to 12 months | the rate of adverse events |
| Sputum microbiota compositions before and after hydrogen therapy | up to 12 months (at baseline, month 6, and month 12) | Sputum microbiota compositions before and after hydrogen therapy. This is an exploratory outcome. |
| Changes in dyshomogeneity (lung clearance index) at month 6 and 12 as compared with baseline | baseline, month 6 and month 12 | Changes in dyshomogeneity (lung clearance index) 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 | Changes in anaerobic threshold (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 | Changes in oxygen pulse (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 | 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 carbon dioxide ventilatory equivalent (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline | baseline, month 6 and month 12 | Changes in carbon dioxide ventilatory equivalent (during cardiopulmonary exercise testing) at month 6 and 12 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 | Changes in 24-hour sputum volume at each visit as compared with baseline |
| Changes in the levels of sputum inflammatory markers (interleukin-6, interleukin-8 and tumor necrosis factor-α) at month 6 and 12 as compared with baseline | baseline, month 6 and month 12 | Changes in the levels of sputum inflammatory markers (interleukin-6, interleukin-8 and tumor necrosis factor-α) 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 | Changes in sputum matrix metalloproteinases (MMP-8, MMP-9, MMP-9/TIMP-1 ratio) levels at month 6 and 12 as compared with baseline |
Countries
China
Contacts
Primary ContactNan-shan Zhong, MD
Backup ContactWei-jie Guan, PhD
Outcome results
None listed