Trial on The Efficacy of Hypertonic Saline on Non-CF CSLD.

November 27, 2023 updated by: Anna Marie Nathan, University of Malaya

Efficacy of Nebulised 5% Hypertonic Saline in Children With Chronic Suppurative Lung Disease

To determine the efficacy of nebulized 5% hypertonic saline on cough severity and quality of life, in children with non-CF CSLD.

Secondary Aims:

To determine the:

  1. Efficacy of nebulized 5% hypertonic saline on airway microbiome, pulmonary exacerbation rate, healthcare utilization, and rescue antibiotics.
  2. Efficacy of nebulized 5% hypertonic saline on lung function
  3. Adverse effects of nebulized 5% hypertonic saline in children

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Aim:

To determine the efficacy of nebulized 5% hypertonic saline on cough severity and quality of life, in children with non-CF CSLD.

Here the investigators will be using validated pediatric cough questionnaires to asses this. Patients will answer these questionnaires at first recruitment ( -1 mth), at randomization (0 month) and after 3 mths of use of the nebulized study drug (+ 3 mths)

Secondary Aims:

To determine the:

  1. Efficacy of nebulized 5% hypertonic saline on the airway microbiome, pulmonary exacerbation rate, healthcare utilization, and rescue antibiotics.

    Here the investigators will be taking history on the exacerbations, use of antibiotics and healthcare utilization before and after use of the hypertonic saline. Furthermore, Nasopharyngeal swabs will be done to review possible changes in microbiota, again before and after use of the 5% HS.

  2. Efficacy of nebulized 5% hypertonic saline on lung function. Here is investigators will be doing portable spirometry ( pre and post bronchodilator).

    Patients will perform at randomization (0 month) and after 3 mths of use of the nebulized study drug (+ 3 mths)

  3. Adverse effects of nebulized 5% hypertonic saline in children HS has been associated with side-effects. The investigators will monitor this. We will asses presence of these symptoms at randomization (0 month) and after 3 mths of use of the nebulized study drug (+ 3 mths) to ensure these are from the nebulizer.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Malaysia
    • Lembah Pantai
      • Kuala Lumpur, Lembah Pantai, Malaysia, 59100
        • University Malaya Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 18 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients < 18 years old
  • Followed up in the paediatric respiratory clinic of UMMC with a diagnosis of CSLD

Exclusion Criteria:

  • Incomplete data or refusal to participate
  • Unwell and/or unable to stop HS and/or antibiotics of any preparation other than azithromycin ( EOD
  • On supplementary oxygen/home ventilation
  • Poorly controlled asthma (as in the GINA guidelines) or bronchoconstriction that precedes the use of hypertonic saline.
  • Oral antibiotics for less than 4 weeks before randomization for medication.
  • Fall in PEFR > 20% post 5% HS challenge test or a positive HS challenge test in young children, as mentioned below.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 5% Hypertonic saline
5% hypertonic saline nebuliser 4 mls twice in a day for 3 months
Drug: Nebulized 5% Hypertonic saline
nebulized 0.9% saline
Other Names:
  • Placebo
Placebo Comparator: Placebo
0.9% saline nebuliser 4 mls twice in a day for 3 months
Drug: Nebulized 5% Hypertonic saline
nebulized 0.9% saline
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Short Parent-proxy cough quality of life (PC-QOL) score
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

Short PCQOL: This is a validated cough quality-of-life(QoL) questionnaire for parents of children with chronic cough, with a translated Malay version. Minimal Important Difference(MID) of 0.9 has been found in the validation study.

The answers are on a Likert scale from 1 (every time) to 7( none). A lower score denotes a lower quality of life.

The patients will answer either the English or the translated Malay version
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
Change in the Chronic Cough-specific QoL(CC-QOL) score
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

Chronic cough-specific QOL: This is a validated cough QoL questionnaire to be answered by children 7 years till 18 years old with a MID of about 1.1. The answers are in a Likert scale from 1 ( every time) to 7( none). A lower score denotes a lower quality of life.

The patients will answer either the English or the translated Malay version
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Airway microbiome
Time Frame: At day 1 of randomization, at 3 months of use of study drug
DNA will be extracted from swabs using the Qiagen DNA Isolation Kit in accordance with the manufacturer's instructions. Bacterial profiling utilised the 16S rRNA gene targeting variable regions V3 - V4 will be carried out using Nextseq 2500 platform. Resulting raw fastq data will be processed using Dada2 R package and exported into phyloseq Rprogram for downstream analysis. The Alpha diversity will be measured using the Shannon and Simpson diversity indices while the beta diversity will be accessed using principle coordinate analysis and Permutational multivariate analysis of variance(PERMANOVA). Differentially abundant taxa will be identified by comparing the fold-change different using DESeq2.
At day 1 of randomization, at 3 months of use of study drug
Number of Exacerbations
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

Defined as having one major and 2 minor OR 2 major criteria irrespective of whether antibiotics are prescribed.

Criteria for exacerbation:

Major: (1) Wet cough over 72 hours, (2) Severe cough over 72 hours Minor: (1) Change in Sputum colour, (2) Chest pain, (3) SOB, (4) Haemoptysis, (5) + ve Chest signs

At -1 month, we will look at the no of exacerbations in the past 1 year. Before the use of the study drug and after 3 months of use of the study drug, we will look at the no of exacerbations in the preceding 1 month and 3 months, respectively.
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
Number of Unscheduled Health Care Visits
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

any unscheduled doctor visits for cough, shortness of breath or any other respiratory associated symptom.

This will be for the last 3 months before day 1 of randomization and after 3 months of use of study drug
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
No of episodes of rescue antibiotics
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

Prescription of antibiotics (including nebulized antibiotics) at least for 3 days for respiratory associated symptoms.

This will be in the past 3 months, before randomization and during the next 3 months, while on the study drug.
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
FEV1
Time Frame: At day 1 of randomization, at 3 months of use of study drug
FEV1 will be performed in sitting position(both pre and post 4 puffs of MDI Salbutamol) using the portable spirometry, performed in clinic. The best spirometric measure of at least 3 reproducible attempts will be recorded for analysis. Reference values from Morris/Polgar will be used with ethnic corrections. FEV1 value will be converted into z-score by using GrowingLungs software.
At day 1 of randomization, at 3 months of use of study drug
FVC
Time Frame: At day 1 of randomization, at 3 months of use of study drug
FVC will be performed in sitting position(both pre and post 4 puffs of MDI Salbutamol) using the portable spirometry, performed in clinic. The best spirometric measure of at least 3 reproducible attempts will be recorded for analysis. Reference values from Morris/Polgar will be used with ethnic corrections. FVC value will be converted into z-score by using GrowingLungs software.
At day 1 of randomization, at 3 months of use of study drug
FEF 25-75%
Time Frame: At day 1 of randomization, at 3 months of use of study drug
FEF 25-75% will be performed in sitting position(both pre and post 4 puffs of MDI Salbutamol) using the portable spirometry, performed in clinic. The best spirometric measure of at least 3 reproducible attempts will be recorded for analysis. Reference values from Morris/Polgar will be used with ethnic corrections. FEF25-75% value will be converted into z-score by using GrowingLungs software.
At day 1 of randomization, at 3 months of use of study drug
PEFR ( pre and post), if possible
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
The best PEFR measure out of 3 reproducible attempts ( both pre and post 4 puffs of MDI Salbutamol), performed when relatively well and stable, will be recorded for analysis.
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
Cough diary
Time Frame: at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

The cough score will be assessed using the Malay version, used in the HOspitalised Pneumonia Extended study, whereby the cough score will be tabulated daily.

The cough diary has recordings for both day time cough: score 0 ( no cough) till score 5 ( Cannot perform most usual day-time activity due to severe coughing).

The night cough is scored score 0 ( no cough) till score 5 ( distressing cough.).

A higher score indicates more severe cough.
at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug
Number of Adverse events
Time Frame: At day 1 of randomization, at 3 months of use of study drug
cough, haemoptysis, sore throat, throat burning, chest tightness, hoarseness of voice.
At day 1 of randomization, at 3 months of use of study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Malaya

Investigators

  • Principal Investigator: Anna M Nathan, UMMC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 4, 2021

Primary Completion (Actual)

August 28, 2023

Study Completion (Actual)

August 28, 2023

Study Registration Dates

First Submitted

February 8, 2021

First Submitted That Met QC Criteria

February 18, 2021

First Posted (Actual)

February 21, 2021

Study Record Updates

Last Update Posted (Estimated)

December 1, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020729-8926

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Not to share

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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