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

NCT04765033 | Completed Phase 4

• 1 other identifier: 2020729-8926
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

Conditions

Bronchiectasis

Keywords

CSLD; Child; Nebuliser; Hypertonic Saline; Outcome; Chronic cough

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (10)

• Airway microbiome

  At day 1 of randomization, at 3 months of use of study drug

• Number of Exacerbations

  at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

• Number of Unscheduled Health Care Visits

  at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

• No of episodes of rescue antibiotics

  at -1 month of randomization, at day 1 of randomization, at 3 months of use of study drug

• FEV1

  At day 1 of randomization, at 3 months of use of study drug

Study Arms (2)

5% Hypertonic saline

ACTIVE COMPARATOR

5% hypertonic saline nebuliser 4 mls twice in a day for 3 months

Drug: Nebulized 5% Hypertonic saline

Placebo

PLACEBO COMPARATOR

0.9% saline nebuliser 4 mls twice in a day for 3 months

Drug: Nebulized 5% Hypertonic saline

Interventions

Nebulized 5% Hypertonic saline DRUG

nebulized 0.9% saline

Also known as: Placebo

5% Hypertonic saline; Placebo

Eligibility Criteria

• Age: 3 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Malaya: lead

Study Sites (1)

University Malaya Medical Centre

Kuala Lumpur, Lembah Pantai, 59100, Malaysia

Location

Related Publications (35)

• 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.

  PMID: 28265556 RESULT

• 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;19(1):561. doi: 10.1186/s12913-019-4414-5.

  PMID: 31409413 RESULT

• Chang AB, Bush A, Grimwood K. Bronchiectasis in children: diagnosis and treatment. Lancet. 2018 Sep 8;392(10150):866-879. doi: 10.1016/S0140-6736(18)31554-X.

  PMID: 30215382 RESULT

• Nathan AM, Muthusamy A, Thavagnanam S, Hashim A, de Bruyne J. Chronic suppurative lung disease in a developing country: impact on child and parent. Pediatr Pulmonol. 2014 May;49(5):435-40. doi: 10.1002/ppul.23001. Epub 2014 Jan 31.

  PMID: 24482322 RESULT

• Kumar A, Lodha R, Kumar P, Kabra SK. Non-cystic fibrosis bronchiectasis in children: clinical profile, etiology and outcome. Indian Pediatr. 2015 Jan;52(1):35-7. doi: 10.1007/s13312-015-0563-8.

  PMID: 25638182 RESULT

• 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.

  PMID: 21885727 RESULT

• Gaillard EA, Carty H, Heaf D, Smyth RL. Reversible bronchial dilatation in children: comparison of serial high-resolution computer tomography scans of the lungs. Eur J Radiol. 2003 Sep;47(3):215-20. doi: 10.1016/s0720-048x(02)00122-5.

  PMID: 12927665 RESULT

• Cole PJ. Inflammation: a two-edged sword--the model of bronchiectasis. Eur J Respir Dis Suppl. 1986;147:6-15.

  PMID: 3533593 RESULT

• Hahn A, Warnken S, Perez-Losada M, Freishtat RJ, Crandall KA. Microbial diversity within the airway microbiome in chronic pediatric lung diseases. Infect Genet Evol. 2018 Sep;63:316-325. doi: 10.1016/j.meegid.2017.12.006. Epub 2017 Dec 7.

  PMID: 29225146 RESULT

• Zemanick ET, Harris JK, Wagner BD, Robertson CE, Sagel SD, Stevens MJ, Accurso FJ, Laguna TA. Inflammation and airway microbiota during cystic fibrosis pulmonary exacerbations. PLoS One. 2013 Apr 30;8(4):e62917. doi: 10.1371/journal.pone.0062917. Print 2013.

  PMID: 23646159 RESULT

• Cox MJ, Allgaier M, Taylor B, Baek MS, Huang YJ, Daly RA, Karaoz U, Andersen GL, Brown R, Fujimura KE, Wu B, Tran D, Koff J, Kleinhenz ME, Nielson D, Brodie EL, Lynch SV. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS One. 2010 Jun 23;5(6):e11044. doi: 10.1371/journal.pone.0011044.

  PMID: 20585638 RESULT

• Prentice BJ, Wales S, Doumit M, Owens L, Widger J. Children with bronchiectasis have poorer lung function than those with cystic fibrosis and do not receive the same standard of care. Pediatr Pulmonol. 2019 Dec;54(12):1921-1926. doi: 10.1002/ppul.24491. Epub 2019 Sep 1.

  PMID: 31475469 RESULT

• Chang AB. Bronchiectasis: so much yet to learn and to do. Paediatr Respir Rev. 2011 Jun;12(2):89-90. doi: 10.1016/j.prrv.2011.01.001. Epub 2011 Feb 2. No abstract available.

  PMID: 21458735 RESULT

• Tarran R, Grubb BR, Parsons D, Picher M, Hirsh AJ, Davis CW, Boucher RC. The CF salt controversy: in vivo observations and therapeutic approaches. Mol Cell. 2001 Jul;8(1):149-58. doi: 10.1016/s1097-2765(01)00286-6.

  PMID: 11511368 RESULT

• Kerem E, Reisman J, Corey M, Canny GJ, Levison H. Prediction of mortality in patients with cystic fibrosis. N Engl J Med. 1992 Apr 30;326(18):1187-91. doi: 10.1056/NEJM199204303261804.

  PMID: 1285737 RESULT

• Reeves EP, Williamson M, O'Neill SJ, Greally P, McElvaney NG. Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis. Am J Respir Crit Care Med. 2011 Jun 1;183(11):1517-23. doi: 10.1164/rccm.201101-0072OC. Epub 2011 Feb 17.

  PMID: 21330456 RESULT

• Elkins MR, Bye PT. Inhaled hypertonic saline as a therapy for cystic fibrosis. Curr Opin Pulm Med. 2006 Nov;12(6):445-52. doi: 10.1097/01.mcp.0000245714.89632.b2.

  PMID: 17053496 RESULT

• Dellon EP, Donaldson SH, Johnson R, Davis SD. Safety and tolerability of inhaled hypertonic saline in young children with cystic fibrosis. Pediatr Pulmonol. 2008 Nov;43(11):1100-1106. doi: 10.1002/ppul.20909.

  PMID: 18828160 RESULT

• Kellett F, Redfern J, Niven RM. Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis. Respir Med. 2005 Jan;99(1):27-31. doi: 10.1016/j.rmed.2004.05.006.

  PMID: 15672845 RESULT

• Kellett F, Robert NM. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. Respir Med. 2011 Dec;105(12):1831-5. doi: 10.1016/j.rmed.2011.07.019. Epub 2011 Oct 22.

  PMID: 22018993 RESULT

• Nicolson CH, Stirling RG, Borg BM, Button BM, Wilson JW, Holland AE. The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis. Respir Med. 2012 May;106(5):661-7. doi: 10.1016/j.rmed.2011.12.021. Epub 2012 Feb 19.

  PMID: 22349069 RESULT

• Paff T, Daniels JM, Weersink EJ, Lutter R, Vonk Noordegraaf A, Haarman EG. A randomised controlled trial on the effect of inhaled hypertonic saline on quality of life in primary ciliary dyskinesia. Eur Respir J. 2017 Feb 23;49(2):1601770. doi: 10.1183/13993003.01770-2016. Print 2017 Feb.

  PMID: 28232410 RESULT

• Sidhu MK, Mandal P, Hill AT. Developing drug therapies in bronchiectasis. Expert Opin Investig Drugs. 2015 Feb;24(2):169-81. doi: 10.1517/13543784.2015.971153. Epub 2014 Oct 11.

  PMID: 25307313 RESULT

• 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.

  PMID: 24521788 RESULT

• Chang AB, Boyce NC, Masters IB, Torzillo PJ, Masel JP. Bronchoscopic findings in children with non-cystic fibrosis chronic suppurative lung disease. Thorax. 2002 Nov;57(11):935-8. doi: 10.1136/thorax.57.11.935.

  PMID: 12403874 RESULT

• 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. Epub 2010 Sep 23.

  PMID: 20864608 RESULT

• 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.

  PMID: 26842959 RESULT

• Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016 Jul;13(7):581-3. doi: 10.1038/nmeth.3869. Epub 2016 May 23.

  PMID: 27214047 RESULT

• McMurdie PJ, Holmes S. phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PLoS One. 2013 Apr 22;8(4):e61217. doi: 10.1371/journal.pone.0061217. Print 2013.

  PMID: 23630581 RESULT

• Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550. doi: 10.1186/s13059-014-0550-8.

  PMID: 25516281 RESULT

• Chang AB, Fong SM, Yeo TW, Ware RS, McCallum GB, Nathan AM, Ooi MH, de Bruyne J, Byrnes CA, Lee B, Nachiappan N, Saari N, Torzillo P, Smith-Vaughan H, Morris PS, Upham JW, Grimwood K. HOspitalised Pneumonia Extended (HOPE) Study to reduce the long-term effects of childhood pneumonia: protocol for a multicentre, double-blind, parallel, superiority randomised controlled trial. BMJ Open. 2019 Apr 24;9(4):e026411. doi: 10.1136/bmjopen-2018-026411.

  PMID: 31023759 RESULT

• 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.

  PMID: 21830316 RESULT

• Stanojevic S, Wade A, Stocks J, Hankinson J, Coates AL, Pan H, Rosenthal M, Corey M, Lebecque P, Cole TJ. Reference ranges for spirometry across all ages: a new approach. Am J Respir Crit Care Med. 2008 Feb 1;177(3):253-60. doi: 10.1164/rccm.200708-1248OC. Epub 2007 Nov 15.

  PMID: 18006882 RESULT

• Walker PP, Key AL. How to perform peak flow and spirometry tests. BMJ. 2016 May 11;353:h6159. doi: 10.1136/sbmj.h6159. No abstract available.

  PMID: 31055386 RESULT

• 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.

  PMID: 23146374 RESULT

MeSH Terms

Conditions

Bronchiectasis; Chronic Cough

Interventions

Saline Solution, Hypertonic

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Cough; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Hypertonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Anna M Nathan

  UMMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant and Professor

Model Details: Double-blind Placebo-controlled trial

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 21, 2021
• Study Start: February 4, 2021
• Primary Completion: August 28, 2023
• Study Completion: August 28, 2023
• Last Updated: December 1, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

MY (1)