Clinical trial NCT02765295: Efficacy and Safety of Hydrogen Inhalation on Bronchiectasis: A Randomized, Multi-center, Double-blind Study
Official title: Efficacy and Safety of Hydrogen Inhalation on Bronchiectasis (HYBRID): A Randomized, Multi-center, Double-blind, Parallel-group Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Bronchiectasis
Acute Exacerbation of Bronchiectasis
Oxidative Stress
Keywords: Hydrogen
Inhalation
bronchiectasis
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2016-05-06
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of bronchiectasis exacerbations (BEs) within 12 months
timeFrame: up to 12 months (1 year)
Secondary outcomes:
measure: Changes in sputum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Time to the first bronchiectasis exacerbations (BEs) within 12 months
timeFrame: up to 12 months
measure: Changes in sputum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in serum oxidant (hydrogen peroxide, reactive oxygen species) levels at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in serum antioxidants levels (catalase, superoxide dismutase and total antioxidant capacity) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in spirometry, including FEV1, FEV1/FVC ratio and MMEF at each visit following randomization as compared with baseline
timeFrame: baseline, month 1, month 3, month 6, month 9 and month 12
measure: Changes in CRP levels at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in quality of life assessed by using Quality-of-Life Questionnaire--Bronchiectasis (QoL-B) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
Other outcomes:
measure: Changes in airway impedance as measured by impulse oscillometry (Z5, R5, R20, X5, Fres and AX at each visit as compared with baseline
timeFrame: baseline, month 1, month 3, month 6, month 9 and month 12
measure: Changes in dyshomogeneity (lung clearance index) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in anaerobic threshold (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in oxygen pulse (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in the difference of arterial and alveolar oxygen partial pressure (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in carbon dioxide ventilatory equivalent (during cardiopulmonary exercise testing) at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Changes in 24-hour sputum volume at each visit as compared with baseline
timeFrame: baseline, month 1, month 3, month 6, month 9 and month 12
measure: 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
timeFrame: baseline, month 6 and month 12
measure: Changes in sputum matrix metalloproteinases (MMP-8, MMP-9, MMP-9/TIMP-1 ratio) levels at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: The rates of Pseudomonas aeruginosa isolated from sputum at baseline and end-of-treatment at month 6 and 12 as compared with baseline
timeFrame: baseline, month 6 and month 12
measure: Sputum microbiota compositions before and after hydrogen therapy
timeFrame: up to 12 months (at baseline, month 6, and month 12)
measure: the rate of adverse events
timeFrame: up to 12 months
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Chengdu
country: China
facility: West China Hospital Affiliateyd to Sichuan Universit
city: Shanghai
country: China
facility: Affiliated Zhongshan Hospital of Fudan University
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
Study officials:
affiliation: Guangzhou Institute of Respiratory Disease
name: Nan-shan Zhong, MD
role: STUDY_CHAIR
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