Nebulised Hypertonic Saline in Children and Young People With Neuromuscular Disease and Cerebral Palsy

• Sponsor: Imperial College London (Other)
• Overall Status: Completed
• CT.gov ID: NCT03623698
• Collaborator: Royal Brompton & Harefield NHS Foundation Trust (Other)
• Enrollment: 24
• Location: 1
• Actual Duration (Months): 15.4
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

Pneumonia, respiratory exacerbations, and chronic pulmonary infection are important causes of emergency admissions, hospitalisations and death in children with Neuromuscular disorders and Cerebral Palsy. Hence, there is a need for research on how to therapeutically aid airway clearance and decrease respiratory exacerbations. Studies have shown that nebulised Hypertonic Saline is well tolerated, reduces pulmonary exacerbations and improves lung function and Lung Clearance Index in patients with Cystic Fibrosis, and enhances mucociliary clearance in asthmatic patients. Nevertheless, to the investigators' knowledge, there is no available data concerning the use of nebulised Hypertonic Saline in the management of children with Neuromuscular disorders and Cerebral Palsy. This study aims to assess the effectiveness of nebulised Hypertonic Saline to decrease hospitalisations and courses of antibiotics in children with Neuromuscular disorders and Cerebral Palsy.

Condition or Disease	Intervention/Treatment	Phase
Neuromuscular Diseases	Drug: Nebulised hypertonic saline

Detailed Description

Chart review of children and young people with Neuromuscular disease or Cerebral Palsy who are cared for in the Royal Brompton Hospital and that have been treated with nebulised hypertonic saline for at least 12 months.

To further complement data from hospital records, two questionnaires will be applied. Parents of children who meet criteria will be asked to complete the following questionnaires:

1. The National Health and Nutrition Examination Survey (NHANES) for Hospitalisation and access to are - HUQ.010; and

2. Questionnaire on Hypertonic Saline treatment.

Children from 10 - 18 years will be asked to complete the Questionnaire on Hypertonic Saline treatment.

AIMS

1. Explore whether treatment with nebulised Hypertonic Saline in children with Neuromuscular disease or Cerebral Palsy decreases respiratory-related complications.

2. Evaluate whether the treatment with nebulised hypertonic saline in children with neuromuscular disease or cerebral palsy improves the ease of airway clearance.

3. Explore how parents of children with Neuromuscular disease and children with Cerebral Palsy perceive the treatment with nebulised hypertonic saline compared with previous management.

Sample Size:

The investigators aim to recruit 40 participants for each group, including children and young people and their parents or legal guardians, as this is a pilot study.

STATISTICAL ANALYSIS PLAN

• Univariate X2 analysis for categorical variables to investigate Courses of antibiotic treatment.

• Univariate X2 analysis for categorical variables to investigate Number of hospitalisations.

• Student t testing will be used to analyse nocturnal oxygenation and ventilation outcomes comparing one year before and after starting treatment with Hypertonic Saline.

• Independent t testing and Mann-Whitney U test to analyse Rate of decline in pulmonary function.

• Cox proportional hazard model to test differences in primary endpoints for different baseline FVC.

• Univarate analysis to analyse Ease of airway clearance.

• Univariate analysis on perception of treatment.

Data and all appropriate documentation will be stored for a minimum of 10 years after the completion of the study, including the follow-up period.

ETHICS APPROVAL The Study Coordination Centre has obtained approval from the Yorkshire & The Humber - Leeds West Research Ethics Committee (REC) and Health Regulatory Authority (HRA). The study also received confirmation of capacity and capability from each participating NHS Trust before accepting participants into the study or any research activity was carried out. The study will be conducted in accordance with the recommendations for physicians involved in research on human subjects adopted by the 18th World Medical Assembly, Helsinki 1964 and later revisions.

CONSENT Consent to enter the study must be sought from each participant only after a full explanation has been given, an information leaflet offered and time allowed for consideration. Signed participant consent should be obtained. The right of the participant to refuse to participate without giving reasons must be respected. After the participant has entered the study the clinician remains free to give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the participant's best interest, but the reasons for doing so should be recorded. In these cases the participants remain within the study for the purposes of follow-up and data analysis. All participants are free to withdraw at any time from the protocol treatment without giving reasons and without prejudicing further treatment.

CONFIDENTIALITY The Chief Investigator will preserve the confidentiality of participants taking part in the study and is registered under the Data Protection Act.

PUBLICATION POLICY Data ownership rights will lie with the institution. Findings of this study will be presented as a Dissertation and will be available through Open Access. The investigators aim to publish findings in peer-review journals.

Study Design

• Study Type: Observational
• Actual Enrollment: 24 participants
• Observational Model: Case-Only
• Time Perspective: Retrospective
• Official Title: A Chart Review Assessing the Effects of Nebulised Hypertonic Saline on Respiratory-related Complications in Children and Young People With Neuromuscular Disease and Cerebral Palsy
• Actual Study Start Date: Jun 15, 2018
• Actual Primary Completion Date: Aug 14, 2019
• Actual Study Completion Date: Sep 26, 2019

Arms and Interventions

Arm	Intervention/Treatment
Before treatment Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)
After treatment Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)	Drug: Nebulised hypertonic saline; Nebulised hypertonic saline used for a period of at least 12 months; Other Names: 3% Sodium Chloride 5% Sodium Chloride 7% Sodium Chloride

Outcome Measures

Primary Outcome Measures

1. Change in Antibiotic Courses [Change from baseline (before treatment) and 12 months after treatment]

   Treatments due to respiratory exacerbations

2. Number of Hospitalsations Due to Respiratory Exacerbations [Change from baseline (before treatment) and 12 months after treatment]

   Number of respiratory exacerbations that required not planned hospitalisation

Secondary Outcome Measures

1. Participant's Perception of Treatment [At 12 months after starting treatment with hypertonic saline]

   Questionnaire: "Hypertonic saline treatment questionnaire". Perception of overall usefulness of nebulised hypertonic saline: "Useful", "Not useful", "I don't know".

2. Parent's or Legal Guardian's Perception of Treatment [At 12 months after starting treatment with hypertonic saline]

   "Hypertonic saline treatment questionnaire for legal guardian". Measures the perception of overall usefulness of nebulised hypertonic saline through a likert scale: Very useful, useful, neither useful or not useful, not useful, not at all useful.

3. Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants [Change from baseline (before treatment) and 12 months after treatment]

   Pictorial visual scale "Facial Rating of perceived exertion Scale". Measures ease of airway clearance. Values range starting in 0 (Extremely easy) to 10 (Extremely hard), including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Numbers are also associated with facial expressions.

4. Score on the Ease of Airway Clearance From Parents or Legal Guardians [Change from baseline (before treatment) and 12 months after treatment]

   Measures ease of airway clearance through a 1-5 likert scale: 1) Very easy, 2) Easy, 3) Neither easy nor difficult, 4) Not easy, 5) Not at all easy.

5. Apnea Index (AI) [Change from baseline (before treatment) and 12 months after treatment]

   The number of apneas recorded during the study per hour of sleep

6. AHI [Change from baseline (before treatment) and 12 months after treatment]

   Nocturnal Apnoea Hipopnea index: total number of apnea events plus hypopnea events divided by the total number of minutes of actual sleep time and then multiplied by 60.

7. %SpO2 [Change from baseline (before treatment) and 12 months after treatment]

   Nocturnal oxygen saturation

8. Nocturnal ODI [Change from baseline (before treatment) and 12 months after treatment]

   Oxygen desaturation index: Number of desaturations per hour of sleep

9. TcPCO2 [Change from baseline (before treatment) and 12 months after treatment]

   Nocturnal Transcutaneous Carbon Dioxide in kPa

10. FEV1/FVC %Predicted Rate of Decline [Change from baseline (before treatment) and 12 months after treatment]

    Rate of decline per year of Tiffenau index

11. FEV1% Predicted Rate of Decline [Change from the baseline (before treatment) and 12 months after treatment]

    Rate of decline of Forced Expiratory Volume in first second (FEV1) percentage of predicted. Rate of decline is a measure of slope of FEV1 percentage predicted. Baseline slope: [(FEV1% at baseline / FEV1% 12 months before treatment) - 1] * 100 After treatment slope: [(FEV1% 12 months after treatment / FEV1% at baseline) - 1] * 100

12. FVC% Predicted Rate of Decline [Change from baseline (before treatment) and 12 months after treatment]

    Rate of decline of Forced Vital Capacity (FVC) percentage of predicted. Rate of decline is a measure of slope of FVC%. Baseline slope: [(FVC% at baseline / FVC% 12 months before treatment) - 1] * 100 After treatment slope: [(FVC% 12 months after treatment / FVC% at baseline) - 1] * 100

13. Peak Expiratory Flow (PEF) [Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline]

    Peak expiratory flow percentage of predicted

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 18 Years
• Sexes Eligible for Study: All

Inclusion Criteria:

• Children with Neuromuscular disease or Cerebral Palsy who have been on treatment with nebulised Hypertonic Saline for at least 12 months.

Exclusion Criteria:

• Children also diagnosed with cystic fibrosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Royal Brompton Hospital	London		United Kingdom	SW36NP

Sponsors and Collaborators

• Imperial College London
• Royal Brompton & Harefield NHS Foundation Trust

Investigators

• Principal Investigator: Natalia Galaz Souza, Professional, Imperial College London

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Apr 4, 2018

More Information

Publications

• Allen J. Pulmonary complications of neuromuscular disease: a respiratory mechanics perspective. Paediatr Respir Rev. 2010 Mar;11(1):18-23. doi: 10.1016/j.prrv.2009.10.002. Epub 2009 Dec 2.
• Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010 May;65(5):379-83. doi: 10.1136/thx.2009.125831.
• Bell CF, Kurosky SK, Candrilli SD. Muscular dystrophy-related hospitalizations among male pediatric patients in the United States. Hosp Pract (1995). 2015;43(3):180-5. doi: 10.1080/21548331.2015.1033375. Epub 2015 Apr 1.
• Boitano LJ. Management of airway clearance in neuromuscular disease. Respir Care. 2006 Aug;51(8):913-22; discussion 922-4. Review.
• Elkins MR, Bye PT. Mechanisms and applications of hypertonic saline. J R Soc Med. 2011 Jul;104 Suppl 1:S2-5. doi: 10.1258/jrsm.2011.s11101. Review.
• Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40.
• Gerdung CA, Tsang A, Yasseen AS 3rd, Armstrong K, McMillan HJ, Kovesi T. Association Between Chronic Aspiration and Chronic Airway Infection with Pseudomonas aeruginosa and Other Gram-Negative Bacteria in Children with Cerebral Palsy. Lung. 2016 Apr;194(2):307-14. doi: 10.1007/s00408-016-9856-5. Epub 2016 Feb 16.
• Lo Mauro A, Aliverti A. Physiology of respiratory disturbances in muscular dystrophies. Breathe (Sheff). 2016 Dec;12(4):318-327. doi: 10.1183/20734735.012716.
• Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med. 2001 Dec 15;164(12):2191-4.
• Yuan JX, McGowan M, Hadjikoumi I, Pant B. Do children with neurological disabilities use more inpatient resources: an observational study. Emerg Themes Epidemiol. 2017 Apr 27;14:5. doi: 10.1186/s12982-017-0059-1. eCollection 2017.

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03623698
• Other Study ID Numbers: 18IC4403
• First Posted: Aug 9, 2018
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Imperial College London: Hypertonic saline; nebulised; children; young people; adolescents; respiratory
• Additional relevant MeSH terms: Cerebral Palsy; Neuromuscular Diseases

Study Results

Participant Flow

Arm/Group Title	Children and Young People With Neuromuscular Disease
Arm/Group Description	Children and young people with neuromuscular disease 18 years old or younger, who had been at least 12 months on prescribed nebulised saline (0.9%, 3%, 6%, and/or 7%) between 2011 and 2019.
Period Title: Overall Study
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Children and Young People With Neuromuscular Disease
Arm/Group Description	Children and young people with neuromuscular disease before nebulised saline was prescribed to them.
Overall Participants	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11 (4.7)
Sex: Female, Male (Count of Participants)
Female	11 45.8%
Male	13 54.2%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
United Kingdom	24 100%
Diagnosis (Count of Participants)
SMA	14 58.3%
Chromosomal myopathy	1 4.2%
Myotubular myopathy	2 8.3%
Nemaline Rod myopathy	1 4.2%
Congenital muscular dystrophy	2 8.3%
LGMD	1 4.2%
Joubert syndrome	1 4.2%
Muscle eye brain disease	1 4.2%
Rett syndrome	1 4.2%
Other characteristics (Count of Participants)
Non-ambulant	21 87.5%
Tracheotomised	3 12.5%
Gastrostomy feeding	17 70.8%
Scoliosis	13 54.2%
Other treatments and medical procedures (Count of Participants)
Antibiotic prophylaxus	12 50%
Dornase alpha	5 20.8%
Home mechanical ventilation	16 66.7%
Mechanically assisted cough	14 58.3%
Tonicity of nebulised prescribed (Count of Participants)
Hypertonic saline only (3%, 6%, 7%)	9 37.5%
Isotonic saline only (0.9%)	4 16.7%
Combination of hypertonic and isotonic saline	11 45.8%

Outcome Measures

1. Primary Outcome

Title	Change in Antibiotic Courses
Description	Treatments due to respiratory exacerbations
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

Two participants had incomplete data for this outcome, and/or their parents could not recall

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9%, 3%, 6%, and/or 7%)
Measure Participants	22	22
Total courses of antibiotics	4	1
Courses of Oral antibiotics	2.50	1.00
Courses of intravenous antibiotics	1.00	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments	Statistical analysis was performed using IBM SPSS Statistics software, version 25. This analysis applies to the category of Total courses of antibiotics.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.500
	Confidence Interval	(2-Sided) 95%; -4.000 to -1.500
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments	Statistical analysis was performed using IBM SPSS Statistics software, version 25. This analysis applies to the category of Total courses of antibiotics.
	Type of Statistical Test	Other
	Comments	Linear mixed-effects model
Statistical Test of Hypothesis	p-Value	0.001
	Comments	95% confidence interval, significance level p-values <0.05. Random effects pre-defined from theory and published data, and AIC was were used to define the best model. Outcome measures: Courses of antibiotics; Fixed effect: nebulised saline treatment.
	Method	Mixed Models Analysis
	Comments	Random effects: age, gender, mechanical ventilation, tracheostomy, gastrostomy, non-ambulant.
Method of Estimation	Estimation Parameter	Restricted Maximum Likelihood (REML)
	Estimated Value	-2.88
	Confidence Interval	(2-Sided) 95%; -4.46 to -1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Hospitalsations Due to Respiratory Exacerbations
Description	Number of respiratory exacerbations that required not planned hospitalisation
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

23/24 patients were analysed for this outcome, because one patient had incomplete records on hospitalisations.

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9%, 3%, 6%, and/or 7%)
Measure Participants	23	23
Median (Inter-Quartile Range) [Hospitalisations]	1	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments	Statistical analysis was performed using IBM SPSS Statistics software, version 25.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-1.00
	Confidence Interval	(2-Sided) 95%; -1.50 to -0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments	Statistical analysis was performed using IBM SPSS Statistics software, version 25.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	95% confidence interval, significance level p-values <0.05. Random effects pre-defined from theory and published data, and AIC was were used to define the best model. Outcome measures: Courses of antibiotics; Fixed effect: nebulised saline treatment.
	Method	Mixed Models Analysis
	Comments	Random effects: age, gender, prolonged mechanical ventilation (nasal or tracheostomy), and antibiotic prophylaxis
Method of Estimation	Estimation Parameter	Restricted Maximum Likelihood (REML)
	Estimated Value	-1.02
	Confidence Interval	(2-Sided) 95%; -1.53 to -0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Participant's Perception of Treatment
Description	Questionnaire: "Hypertonic saline treatment questionnaire". Perception of overall usefulness of nebulised hypertonic saline: "Useful", "Not useful", "I don't know".
Time Frame	At 12 months after starting treatment with hypertonic saline

Outcome Measure Data

Analysis Population Description

Applied to all participants aged 10-15 years who were able to communicate their views.

Arm/Group Title	Children and Young People With Neuromuscular Disease
Arm/Group Description	Children and young people with neuromuscular disease 18 years old or younger, who had been at least 12 months on prescribed nebulised saline (0.9%, 3%, 6%, and/or 7%) between 2011 and 2019.
Measure Participants	11
Useful	11 45.8%
Not useful	0 0%
I don't know	0 0%

4. Secondary Outcome

Title	Parent's or Legal Guardian's Perception of Treatment
Description	"Hypertonic saline treatment questionnaire for legal guardian". Measures the perception of overall usefulness of nebulised hypertonic saline through a likert scale: Very useful, useful, neither useful or not useful, not useful, not at all useful.
Time Frame	At 12 months after starting treatment with hypertonic saline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Parent's or Legal Guardians
Arm/Group Description	One parent or legal guardian for each of the study participants
Measure Participants	24
Very useful	15 62.5%
useful	9 37.5%
neither useful or not useful	0 0%
not useful	0 0%
not at all useful	0 0%

5. Secondary Outcome

Title	Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants
Description	Pictorial visual scale "Facial Rating of perceived exertion Scale". Measures ease of airway clearance. Values range starting in 0 (Extremely easy) to 10 (Extremely hard), including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Numbers are also associated with facial expressions.
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	11	11
Mean (Full Range) [score on a scale]	6.45	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-4.50
	Confidence Interval	(2-Sided) 95%; -5.50 to -3.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Score on the Ease of Airway Clearance From Parents or Legal Guardians
Description	Measures ease of airway clearance through a 1-5 likert scale: 1) Very easy, 2) Easy, 3) Neither easy nor difficult, 4) Not easy, 5) Not at all easy.
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Parents of children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Parents pf children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	24	24
Mean (Full Range) [score on a scale]	4.21	2.13

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.00
	Confidence Interval	(2-Sided) 95%; -2.5 to -2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Apnea Index (AI)
Description	The number of apneas recorded during the study per hour of sleep
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

3/24 patients had records for this outcome

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9%, 3%, 6%, and/or 7%)
Measure Participants	3	3
Mean (Standard Deviation) [Events per hour of sleep]	4.87 (1.02)	0.40 (0.4)

8. Secondary Outcome

Title	AHI
Description	Nocturnal Apnoea Hipopnea index: total number of apnea events plus hypopnea events divided by the total number of minutes of actual sleep time and then multiplied by 60.
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	3	4
Mean (Standard Deviation) [Events per hour of sleep]	8.53 (1.70)	1.38 (0.99)

9. Secondary Outcome

Title	%SpO2
Description	Nocturnal oxygen saturation
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

21/24 patients had complete records for this outcome

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9%, 3%, 6%, and/or 7%)
Measure Participants	21	21
Mean (Standard Deviation) [percentage of SpO2]	96.55 (1.92)	96.53 (1.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.97
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Nocturnal ODI
Description	Oxygen desaturation index: Number of desaturations per hour of sleep
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

21/24 patients had complete records for this outcome

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	21	21
Mean (Standard Deviation) [Events per hour of sleep]	4.26 (3.42)	3.32 (3.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.47
	Confidence Interval	(2-Sided) 95%; -3.26 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	TcPCO2
Description	Nocturnal Transcutaneous Carbon Dioxide in kPa
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

21/24 patients had complete records for this outcome

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9%, 3%, 6%, and/or 7%)
Measure Participants	21	21
Mean (Standard Deviation) [Kilopascal (kPa)]	5.77 (0.95)	6.00 (1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Before Treatment, After Treatment
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	FEV1/FVC %Predicted Rate of Decline
Description	Rate of decline per year of Tiffenau index
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

5/24 patients had complete records for this outcome

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	5	5
Median (Inter-Quartile Range) [percentage of predicted]	97.37	98.89

13. Secondary Outcome

Title	FEV1% Predicted Rate of Decline
Description	Rate of decline of Forced Expiratory Volume in first second (FEV1) percentage of predicted. Rate of decline is a measure of slope of FEV1 percentage predicted. Baseline slope: [(FEV1% at baseline / FEV1% 12 months before treatment) - 1] * 100 After treatment slope: [(FEV1% 12 months after treatment / FEV1% at baseline) - 1] * 100
Time Frame	Change from the baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	2	5
Median (Inter-Quartile Range) [percentage of predicted]	-8.03	4.00

14. Secondary Outcome

Title	FVC% Predicted Rate of Decline
Description	Rate of decline of Forced Vital Capacity (FVC) percentage of predicted. Rate of decline is a measure of slope of FVC%. Baseline slope: [(FVC% at baseline / FVC% 12 months before treatment) - 1] * 100 After treatment slope: [(FVC% 12 months after treatment / FVC% at baseline) - 1] * 100
Time Frame	Change from baseline (before treatment) and 12 months after treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	2	3
Median (Inter-Quartile Range) [percentage of predicted]	-7.44	7.00

15. Secondary Outcome

Title	Peak Expiratory Flow (PEF)
Description	Peak expiratory flow percentage of predicted
Time Frame	Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Before Treatment	After Treatment
Arm/Group Description	Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline (0.9% - 7%)	Children and young people with neuromuscular disease during the 12 months after being prescribed treatment with nebulised saline (0.9% - 7%)
Measure Participants	6	5
Median (Inter-Quartile Range) [percentage of predicted]	43.5	47

Adverse Events

Time Frame	This was a retrospective study. Adverse events data was not collected.
Adverse Event Reporting Description	This was a retrospective study. Adverse events data was not collected.
Arm/Group Title	Children and Young People With Neuromuscular Disease
Arm/Group Description	Children and young people with neuromuscular disease 18 years old or younger, who had been at least 12 months on prescribed nebulised saline (0.9%, 3%, 6%, and/or 7%) between 2011 and 2019.
All Cause Mortality
	Children and Young People With Neuromuscular Disease
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Serious Adverse Events
	Children and Young People With Neuromuscular Disease
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Children and Young People With Neuromuscular Disease
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

This was a retrospective study, with potential for bias from self-selection. Each patient was used as their own control. The use of questionnaires had the potential for recall bias. This study did not have adherence data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.