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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| hydrogen inhalation | Active Comparator | 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 mixture 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). Usual care referred to mucolytics (see below for details) alone or plus chest physiotherapy. |
|
| oxygen inhalation | Sham Comparator | Oxygen will be generated by an instrument provided by the sponsor, that would be capable of generating oxygen equivalent to that generated by the MUNHO (3L/min mixed gas containing 33.3% oxygen). Usual care referred to mucolytics [[ambroxool (30mg thrice daily), or N-acetylcysteine (0.2g thrice daily)/ serrapeptase (10mg thrice daily), or carbocisteine (500mg thrice daily)] alone or in combination with chest physiotherapy.](streamdown:incomplete-link) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| medical ultrasonic hydrogen/oxygen nebulizer (MUNHO) | Device | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of bronchiectasis exacerbations (BEs) within 12 months | Frequency of bronchiectasis exacerbations (BEs) within 12 months | up to 12 months (1 year) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Time to the first bronchiectasis exacerbations (BEs) within 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Nan-shan Zhong, MD | Contact | +86-13609003622 | nanshan@vip.163.com | |
| Wei-jie Guan, PhD | Contact | +86-13826042052 | battery203@163.com |
| Name | Affiliation | Role |
|---|---|---|
| Nan-shan Zhong, MD | Guangzhou Institute of Respiratory Disease | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| First Affiliated Hospital of Guangzhou Medical University | Recruiting | Guangzhou | Guangdong | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20627931 | Background | Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119. | |
| 19357155 | Background | Loebinger MR, Wells AU, Hansell DM, Chinyanganya N, Devaraj A, Meister M, Wilson R. Mortality in bronchiectasis: a long-term study assessing the factors influencing survival. Eur Respir J. 2009 Oct;34(4):843-9. doi: 10.1183/09031936.00003709. Epub 2009 Apr 8. |
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|
| Medical molecular mesh oxygen generator | Device | 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. |
|
|
Time to the first bronchiectasis exacerbations (BEs) within 12 months |
| up to 12 months |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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 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 |
| 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 |
| 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) |
| the rate of adverse events | the rate of adverse events | up to 12 months |
| The Second Affiliated Hospital of Guangzhou Medical University | Recruiting | Guangzhou | Guangdong | China |
|
| West China Hospital Affiliateyd to Sichuan Universit | Not yet recruiting | Chengdu | China |
|
| Affiliated Zhongshan Hospital of Fudan University | Not yet recruiting | Shanghai | China |
|
| Shanghai Pulmonary Hospital | Not yet recruiting | Shanghai | China |
|
| 11986413 | Background | Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available. |
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| ID | Term |
|---|---|
| D001987 | Bronchiectasis |
| D053120 | Respiratory Aspiration |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D012120 | Respiration Disorders |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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