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

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Bronchiectasis; Airway Clearance Impairment
• Intervention / Treatment: Other: Hypertonic saline at 6%; Other: Airway clearance techniques (oscillating positive expiratory pressure therapy)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Beatriz Herrero-Cortina; Phone Number: 34653051357; Email: Beafisiorespi@gmail.com

Study Locations

• Spain
  • Barcelona, Spain
    • Hospital Clínic
  • Zaragoza, Spain
    • Beatriz Herrero Cortina
    • Contact: Beatriz Herrero-Cortina
    • Principal Investigator: Beatriz Herrero-Cortina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years or older
2. a total score less than 16 on the Leicester Cough Questionnaire
3. chronic daily expectoration over at least 3 months
4. being in a period of clinical stability during the previous 4 weeks
5. presenting a forced expiratory volume in 1 second (FEV1) value greater than 40% of predicted or >1 L
6. 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:

1. having received nebulised mucoactive treatment during the previous year
2. frequent haemoptysis (≥ 2 times/month)
3. diagnosis or suspicion of cystic fibrosis by genetic study or sweat test
4. being under active treatment for nontuberculous mycobacteria (NTM)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single daily session (Hypertonic saline + airway clearance techniques); 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%; 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.; Other: Airway clearance techniques (oscillating positive expiratory pressure therapy); 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
ACTIVE_COMPARATOR: Twice daily session (Hypertonic saline + airway clearance techniques); 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%; 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.; Other: Airway clearance techniques (oscillating positive expiratory pressure therapy); 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lung Function	Forced spirometry (forced expiratory volume in 1 second [FEV1] and forced vital capacity [FVC]) will be perform for safety analysis following the American Thoracic Society / European Respiratory Society guidelines	Baseline point, 1 month, 3 months, 6 months
Adverse events during sessions	Adverse events during nebulisation period will be recorded using a Likert scale and participants will also complete the Self-Reported Medication Scale	Baseline point, 1 month, 3 months, 6 months

Collaborators and Investigators

• Sponsor: Hospital Clínico Universitario Lozano Blesa
• Collaborators: Hospital Clinic of Barcelona; Universidad San Jorge
• Investigators: Principal Investigator: Victoria Alcaraz-Serrano, Hospital Clinic of Barcelona; Principal Investigator: Beatriz Herrero-Cortina, Hospital Clinico Universitario Lozano Blesa

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): July 1, 2021
• Primary Completion (ANTICIPATED): June 1, 2023
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (ACTUAL): May 28, 2021

Study Record Updates

• Last Update Posted (ACTUAL): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Hypertonic saline; Hyperosmolar agents; Airway clearance techniques; Oscillating positive expiratory pressure
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: HS_nonInferiority

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No