Sputum Clearance Effects of Hypertonic Saline in Non-cystic Fibrosis Bronchiectasis

Sputum Clearance Effects of Hypertonic Saline in Non-cystic Fibrosis Bronchiectasis: a Randomized, Double-blind, Crossover Trial

This study aims to analyze whether the hypertonic saline nebulization enhances sputum clearance effects, reduces the impact on cough severity and their level of safety and tolerability in a population with non-cystic fibrosis bronchiectasis (NCFBE). In addition, this trial aims to compare these health outcomes among 3 nebulized solutions: hypertonic saline (7%); hyaluronic acid + hypertonic saline (7%); isotonic saline (0,9%).

Study Overview

• Status: Completed
• Conditions: Bronchiectasis
• Intervention / Treatment: Other: Hypertonic saline solution; Other: Hyaneb solution; Other: Isotonic saline solution

Detailed Description

The present study will be a randomized, double-blind, crossover trial. Each nebulized solution [hypertonic saline (7%); hyaluronic acid + hypertonic saline (7%); isotonic saline (0,9%)] will be administrated during 4 days. After each inhalation, all patients will carry out a bronchial drainage session (autogenic drainage technique). All patients recruited will perform the three arms of intervention. In this way, each patient will be able to act as his/her own control.

A 7 days washout period will be required among the different solutions to avoid carryover effects.

During the study period the patients' pharmacological treatment remained unchanged.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic

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. Non-cystic Fibrosis bronchiectasis (NCFBE) diagnosed by High Resolution Computed Tomographic
2. Mean sputum production ≥ 10 ml /24h.
3. Clinical stability in the last 4 weeks
4. To be able to understand how to perform inhalation and the physiotherapy session.
5. To be able to provide written, informed consent

Exclusion Criteria:

1. Forced expiratory volume in 1 second < 30% pred. ; Total lung capacity < 45% pred.
2. Performing nebulization with any hyperosmolar agents, previously
3. Allergic bronchopulmonary aspergillosis diagnosis
4. Not to be able to overcome the safety test pre-intervention (oxygen saturation levels drop to < 90% and/or forced expiratory volume in 1 second decline more than < 12% from baseline during the nebulization process)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hypertonic saline solution; Hypertonic saline (7%) solution (5 ml) will be nebulized by all patients in a randomized order. Immediately after, patients will perform a bronchial drainage session. The airway clearance technique selected will be autogenic drainage (AD). Both patients and physiotherapist will be blind to the intervention.	Other: Hypertonic saline solution; All patients will perform 4 sessions during the same week. Each session will be include: inhalation period + bronchial drainage period. 20 minutes will be spent to perform the inhalation period. Moreover, 30 minutes will be spent to complete the bronchial drainage session post-inhalation.
Active Comparator: Hyaneb solution; Hyaneb (acid hyaluronic + hypertonic saline [7%]) solution (5 ml) will be nebulized by all patients in a randomized order. Immediately after, patients will perform a bronchial drainage session. The airway clearance technique selected will be autogenic drainage (AD). Both patients and physiotherapist will be blind to the intervention.	Other: Hyaneb solution; All patients will perform 4 sessions during the same week. Each session will be include: inhalation period + bronchial drainage period. 20 minutes will be spent to perform the inhalation period. Moreover, 30 minutes will be spent to complete the bronchial drainage session post-inhalation.
Placebo Comparator: Isotonic saline solution; Isotonic saline (0,9%) solution (5 ml) will be nebulized by all patients in a randomized order. Immediately after, patients will perform a bronchial drainage session. The airway clearance technique selected will be autogenic drainage (AD). Both patients and physiotherapist will be blind to the intervention.	Other: Isotonic saline solution; All patients will perform 4 sessions during the same week. Each session will be include: inhalation period + bronchial drainage period. 20 minutes will be spent to perform the inhalation period. Moreover, 30 minutes will be spent to complete the bronchial drainage session post-inhalation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wet sputum production	Sputum collected during nebulization period and physiotherapy session	1h wet sputum production (g)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wet sputum production	Spontaneous sputum expectorated during the following 24h after intervention	24h wet sputum production (g)
Impact on cough severity (Leicester Cough Questionnaire)	Self-administered questionnaire (Leicester Cough Questionnaire)	One week
Lung function (Forced spirometry)	Forced spirometry: forced expiratory volume in 1 second, Forced vital capacity, Forced expiratory flow 25-75	One week
Safety and tolerability (Adverse events)	Adverse events registration during the nebulization process (heart rate, saturation and dyspnoea)	20 minutes

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients´preference (Likert test)	Self-administered "Likert test" at the end of the trial	5 weeks

Collaborators and Investigators

• Sponsor: Hospital Clinic of Barcelona
• Investigators: Principal Investigator: Eva Polverino, Dr., Hospital Clínic

Publications and helpful links

General Publications

• Herrero-Cortina B, Alcaraz-Serrano V, Torres A, Polverino E. Reliability and Minimum Important Difference of Sputum Weight in Bronchiectasis. Respir Care. 2020 Oct;65(10):1478-1487. doi: 10.4187/respcare.07175. Epub 2020 Feb 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: March 13, 2015
• First Submitted That Met QC Criteria: March 18, 2015
• First Posted (Estimate): March 19, 2015

Study Record Updates

• Last Update Posted (Estimate): November 15, 2016
• Last Update Submitted That Met QC Criteria: November 11, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Tolerability; Hypertonic saline; Sputum clearance; Cough severity; Acid hyaluronic
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis; Pharmaceutical Solutions
• Other Study ID Numbers: Hyperosmolar_NCFB