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

Bronchiectasis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04765033
• Other study ID #: 2020729-8926
• Status: Completed
• Phase: Phase 4
• Start date: February 4, 2021
• Est. completion date: August 28, 2023

Study information

• Verified date: November 2023
• Source: University of Malaya
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: August 28, 2023
• Est. primary completion date: August 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Drug:
• Nebulized 5% Hypertonic saline
nebulized 0.9% saline

Locations

Country	Name	City	State
Malaysia	University Malaya Medical Centre	Kuala Lumpur	Lembah Pantai

Sponsors (1)

Lead Sponsor	Collaborator
University of Malaya

Country where clinical trial is conducted

Malaysia, 

References & Publications (35)

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Goyal V, Grimwood K, Marchant J, Masters IB, Chang AB. Does failed chronic wet cough response to antibiotics predict bronchiectasis? Arch Dis Child. 2014 Jun;99(6):522-5. doi: 10.1136/archdischild-2013-304793. Epub 2014 Feb 12. — View Citation

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Kapur N, Masel JP, Watson D, Masters IB, Chang AB. Bronchoarterial ratio on high-resolution CT scan of the chest in children without pulmonary pathology: need to redefine bronchial dilatation. Chest. 2011 Jun;139(6):1445-1450. doi: 10.1378/chest.10-1763. — View Citation

Kapur N, Masters IB, Morris PS, Galligan J, Ware R, Chang AB. Defining pulmonary exacerbation in children with non-cystic fibrosis bronchiectasis. Pediatr Pulmonol. 2012 Jan;47(1):68-75. doi: 10.1002/ppul.21518. Epub 2011 Aug 9. — View Citation

Kapur N, Masters IB, Newcombe P, Chang AB. The burden of disease in pediatric non-cystic fibrosis bronchiectasis. Chest. 2012 Apr;141(4):1018-1024. doi: 10.1378/chest.11-0679. Epub 2011 Sep 1. — View Citation

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Lovie-Toon YG, Grimwood K, Byrnes CA, Goyal V, Busch G, Masters IB, Marchant JM, Buntain H, O'Grady KF, Chang AB. Health-resource use and quality of life in children with bronchiectasis: a multi-center pilot cohort study. BMC Health Serv Res. 2019 Aug 13; — View Citation

McCallum GB, Binks MJ. The Epidemiology of Chronic Suppurative Lung Disease and Bronchiectasis in Children and Adolescents. Front Pediatr. 2017 Feb 20;5:27. doi: 10.3389/fped.2017.00027. eCollection 2017. — View Citation

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Newcombe PA, Sheffield JK, Chang AB. Parent cough-specific quality of life: development and validation of a short form. J Allergy Clin Immunol. 2013 Apr;131(4):1069-74. doi: 10.1016/j.jaci.2012.10.004. Epub 2012 Nov 10. — View Citation

Newcombe PA, Sheffield JK, Petsky HL, Marchant JM, Willis C, Chang AB. A child chronic cough-specific quality of life measure: development and validation. Thorax. 2016 Aug;71(8):695-700. doi: 10.1136/thoraxjnl-2015-207473. Epub 2016 Feb 3. — View Citation

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* Note: There are 35 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the Short Parent-proxy cough quality of life (PC-QOL) score	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
Primary	Change in the Chronic Cough-specific QoL(CC-QOL) score	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	Airway microbiome	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
Secondary	Number of Exacerbations	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
Secondary	Number of Unscheduled Health Care Visits	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
Secondary	No of episodes of rescue antibiotics	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
Secondary	FEV1	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
Secondary	FVC	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
Secondary	FEF 25-75%	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
Secondary	PEFR ( pre and post), if possible	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
Secondary	Cough diary	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
Secondary	Number of Adverse events	cough, haemoptysis, sore throat, throat burning, chest tightness, hoarseness of voice.	At day 1 of randomization, at 3 months of use of study drug