Is a Single Daily Session Combining HS + Physio Sufficient to Obtain Long-term Clinical Benefits in Bronchiectasis?

Study Overview
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Brief Summary
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The present study will aim to find out whether a home treatment in people with bronchiectasis consisting of a single daily session to facilitate expectoration (combining nebulization of hypertonic saline (HS) at 6% followed by airway clearance techniques) is at least as effective as performing two sessions per day following the same process in each of the sessions, during a period of 6 months.

Detailed Description
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A non-inferiority randomised clinical trial (single-blind) will be conducted. At least 50 participants will be recruited from the outpatient clinics of the Hospital Clinic in Barcelona and the Clinical University Hospital in Zaragoza. The experimental group will nebulize once/day the hypertonic saline (HS) solution followed by airway clearance exercises (15 min) for 6 months. The control group will follow the same procedure, but the frequency of the sessions will be twice a day (reference as usual clinical practice). The main study outcomes will be: (1) cough severity (primary endpoint), symptoms and quality of life; (2) functional exercise capacity; (3) time to first exacerbation and total number of exacerbations; (4) indirect measures of mucociliary transport (rheology and concentration of solids in sputum samples); (5) inflammatory parameters; (5) tolerance, safety and adherence to treatment. Measurements will be taken at baseline (prior to randomization), at 1 month, 3 months, and 6 months. Finally, hypothesis testing will be performed using a linear mixed model (2x3) of repeated measures, establishing a priori a margin of non-inferiority.

Official Title
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Is a Single Daily Session Combining Hypertonic Saline Nebulisation and Airway Clearance Techniques Sufficient to Obtain Long-term Clinical Benefits in People With Bronchiectasis? A Randomised Non-inferiority Trial.

Conditions
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Bronchiectasis, Airway Clearance Impairment

Intervention / Treatment
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* Other: Hypertonic saline at 6%
* Other: Airway clearance techniques (oscillating positive expiratory pressure therapy)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older a total score less than 16 on the Leicester Cough Questionnaire chronic daily expectoration over at least 3 months being in a period of clinical stability during the previous 4 weeks presenting a forced expiratory volume in 1 second (FEV1) value greater than 40% of predicted or >1 L obtaining informed consent. In addition, all participants will have had to satisfactorily pass the tolerability tests, which will be performed twice: i) on the first day; ii) and the following week. Exclusion Criteria: having received nebulised mucoactive treatment during the previous year frequent haemoptysis (≥ 2 times/month) diagnosis or suspicion of cystic fibrosis by genetic study or sweat test being under active treatment for nontuberculous mycobacteria (NTM)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A non-inferiority randomized clinical trial (single-blinded assessor).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single daily session (Hypertonic saline + airway clearance techniques)<br>The experimental group will perform a daily session at home including nebulisation of 5 mL of hypertonic saline (at 6%) followed by 15 min of airway clearance techniques (oscillating positive expiratory pressure therapy) for 6 months. | Other: Hypertonic saline at 6%<br>* Participants will start the sessions by inhaling a short-acting bronchodilator or an anticholinergic to avoid the presence of bronchospasm during nebulisation. The hypertonic solution (at 6%) will be administered through the Turbo Boy nebuliser (Pari®). The intervention will take place at home.<br>Other: Airway clearance techniques (oscillating positive expiratory pressure therapy)<br>* Following nebulisation, participants will perform airway clearance techniques using an oscillating positive expiratory pressure device for at least 15 minutes. The intervention will take place at home<br>|
| Active Comparator: Twice daily session (Hypertonic saline + airway clearance techniques)<br>The control group will perform two daily sessions at home involving nebulisation of 5 mL of hypertonic saline (at 6%) followed by 15 min of airway clearance techniques (oscillating positive expiratory pressure therapy) for 6 months. | Other: Hypertonic saline at 6%<br>* Participants will start the sessions by inhaling a short-acting bronchodilator or an anticholinergic to avoid the presence of bronchospasm during nebulisation. The hypertonic solution (at 6%) will be administered through the Turbo Boy nebuliser (Pari®). The intervention will take place at home.<br>Other: Airway clearance techniques (oscillating positive expiratory pressure therapy)<br>* Following nebulisation, participants will perform airway clearance techniques using an oscillating positive expiratory pressure device for at least 15 minutes. The intervention will take place at home<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of coughing on quality of life | The Leicester Cough Questionnaire (LCQ) will be used to assess the daily cough impact | 6 months after starting the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of coughing on quality of life | The Leicester Cough Questionnaire (LCQ) will be used to assess the daily cough impact | Baseline point, 1 month and 3 months after starting the intervention | 
| Disease-specific quality of life questionnaire | The Quality of life of Bronchiectasis (QoL-B) questionnaire will be used to evaluate the quality of life | Baseline point, 1 month, 3 months and 6 months after starting the intervention | 
| Disease-specific symptoms questionnaire | The Bronchiectasis Impact Measure (BIM) outcome measure will be used to analyse the symptoms | Baseline point, 1 month, 3 months and 6 months after starting the intervention | 
| Exercise capacity | The sit to stand test (1 minute) will be used to assess the exercise capacity | Baseline point, 1 month, 3 months and 6 months after starting the intervention | 
| Exercise capacity | The six minute walk distance (6MWT) will be used to assess the exercise capacity | Baseline point | 
| Exacerbations | The number of exacerbations, the severity of exacerbations (hospital admission) and the time to the first exacerbation will be recorded prospectively | From baseline point to the end of the intervention (6 months) | 
| Biophysical properties of spontaneous sputum samples | Spontaneous sputum samples will be collected to analyse the main biophysical markers | Baseline point, 1 month, 3 months, 6 months | 
| Inflammation markers (airway inflammation and systemic inflammation) | Blood and salivary samples will be collected to analyse the main inflammatory markers (neutrophil elastase, cytokines, peptides) | Baseline point, 1 month, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Airway clearance techniques, Hypertonic saline, Hyperosmolar agents, Oscillating positive expiratory pressure