Neuromuscular Diseases
Conditions
Keywords
Hypertonic saline, nebulised, children, young people, adolescents, respiratory
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.
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.
Interventions
DRUGNebulised hypertonic saline
Nebulised hypertonic saline used for a period of at least 12 months
Sponsors
Royal Brompton & Harefield NHS Foundation Trust
Imperial College London
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Antibiotic Courses | Change from baseline (before treatment) and 12 months after treatment | Treatments due to respiratory exacerbations |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| 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. |
| %SpO2 | Change from baseline (before treatment) and 12 months after treatment | Nocturnal oxygen saturation |
| 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. |
| TcPCO2 | Change from baseline (before treatment) and 12 months after treatment | Nocturnal Transcutaneous Carbon Dioxide in kPa |
| FEV1/FVC %Predicted Rate of Decline | Change from baseline (before treatment) and 12 months after treatment | Rate of decline per year of Tiffenau index |
| 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 |
| 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 |
| 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 |
| Nocturnal ODI | Change from baseline (before treatment) and 12 months after treatment | Oxygen desaturation index: Number of desaturations per hour of sleep |
| 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Children and Young People With Neuromuscular Disease Children and young people with neuromuscular disease before nebulised saline was prescribed to them. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | Children and Young People With Neuromuscular Disease | — |
|---|---|---|
| Age, Continuous | 11 years STANDARD_DEVIATION 4.7 | — |
| Diagnosis Chromosomal myopathy | 1 Participants | — |
| Diagnosis Congenital muscular dystrophy | 2 Participants | — |
| Diagnosis Joubert syndrome | 1 Participants | — |
| Diagnosis LGMD | 1 Participants | — |
| Diagnosis Muscle eye brain disease | 1 Participants | — |
| Diagnosis Myotubular myopathy | 2 Participants | — |
| Diagnosis Nemaline Rod myopathy | 1 Participants | — |
| Diagnosis Rett syndrome | 1 Participants | — |
| Diagnosis SMA | 14 Participants | — |
| Other characteristics Gastrostomy feeding | 17 Participants | — |
| Other characteristics Non-ambulant | 21 Participants | — |
| Other characteristics Scoliosis | 13 Participants | — |
| Other characteristics Tracheotomised | 3 Participants | — |
| Other treatments and medical procedures Antibiotic prophylaxus | 12 Participants | — |
| Other treatments and medical procedures Dornase alpha | 5 Participants | — |
| Other treatments and medical procedures Home mechanical ventilation | 16 Participants | — |
| Other treatments and medical procedures Mechanically assisted cough | 14 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United Kingdom | 24 Participants | — |
| Sex: Female, Male Female | 11 Participants | — |
| Sex: Female, Male Male | 13 Participants | — |
| Tonicity of nebulised prescribed Combination of hypertonic and isotonic saline | 11 Participants | — |
| Tonicity of nebulised prescribed Hypertonic saline only (3%, 6%, 7%) | 9 Participants | — |
| Tonicity of nebulised prescribed Isotonic saline only (0.9%) | 4 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Change in Antibiotic Courses
Treatments due to respiratory exacerbations
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: Two participants had incomplete data for this outcome, and/or their parents could not recall
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Before Treatment | Change in Antibiotic Courses | Courses of Oral antibiotics | 2.50 Courses of antibiotics |
| Before Treatment | Change in Antibiotic Courses | Courses of intravenous antibiotics | 1.00 Courses of antibiotics |
| Before Treatment | Change in Antibiotic Courses | Total courses of antibiotics | 4 Courses of antibiotics |
| After Treatment | Change in Antibiotic Courses | Total courses of antibiotics | 1 Courses of antibiotics |
| After Treatment | Change in Antibiotic Courses | Courses of Oral antibiotics | 1.00 Courses of antibiotics |
| After Treatment | Change in Antibiotic Courses | Courses of intravenous antibiotics | 0.00 Courses of antibiotics |
Comparison: Statistical analysis was performed using IBM SPSS Statistics software, version 25.~This analysis applies to the category of Total courses of antibiotics.p-value: <0.00195% CI: [-4, -1.5]Wilcoxon (Mann-Whitney)
Comparison: Statistical analysis was performed using IBM SPSS Statistics software, version 25.~This analysis applies to the category of Total courses of antibiotics.p-value: 0.00195% CI: [-4.46, -1.29]Mixed Models Analysis
Primary
Number of Hospitalsations Due to Respiratory Exacerbations
Number of respiratory exacerbations that required not planned hospitalisation
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 23/24 patients were analysed for this outcome, because one patient had incomplete records on hospitalisations.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Before Treatment | Number of Hospitalsations Due to Respiratory Exacerbations | 1 Hospitalisations |
| After Treatment | Number of Hospitalsations Due to Respiratory Exacerbations | 0 Hospitalisations |
Comparison: Statistical analysis was performed using IBM SPSS Statistics software, version 25.p-value: 0.00195% CI: [-1.5, -0.5]Wilcoxon (Mann-Whitney)
Comparison: Statistical analysis was performed using IBM SPSS Statistics software, version 25.p-value: <0.00195% CI: [-1.53, -0.52]Mixed Models Analysis
Secondary
AHI
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Treatment | AHI | 8.53 Events per hour of sleep | Standard Deviation 1.7 |
| After Treatment | AHI | 1.38 Events per hour of sleep | Standard Deviation 0.99 |
Secondary
Apnea Index (AI)
The number of apneas recorded during the study per hour of sleep
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 3/24 patients had records for this outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Treatment | Apnea Index (AI) | 4.87 Events per hour of sleep | Standard Deviation 1.02 |
| After Treatment | Apnea Index (AI) | 0.40 Events per hour of sleep | Standard Deviation 0.4 |
Secondary
FEV1/FVC %Predicted Rate of Decline
Rate of decline per year of Tiffenau index
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 5/24 patients had complete records for this outcome
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Before Treatment | FEV1/FVC %Predicted Rate of Decline | 97.37 percentage of predicted |
| After Treatment | FEV1/FVC %Predicted Rate of Decline | 98.89 percentage of predicted |
Secondary
FEV1% Predicted Rate of Decline
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Before Treatment | FEV1% Predicted Rate of Decline | -8.03 percentage of predicted |
| After Treatment | FEV1% Predicted Rate of Decline | 4.00 percentage of predicted |
Secondary
FVC% Predicted Rate of Decline
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
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Before Treatment | FVC% Predicted Rate of Decline | -7.44 percentage of predicted |
| After Treatment | FVC% Predicted Rate of Decline | 7.00 percentage of predicted |
Secondary
Nocturnal ODI
Oxygen desaturation index: Number of desaturations per hour of sleep
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 21/24 patients had complete records for this outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Treatment | Nocturnal ODI | 4.26 Events per hour of sleep | Standard Deviation 3.42 |
| After Treatment | Nocturnal ODI | 3.32 Events per hour of sleep | Standard Deviation 3.33 |
p-value: 0.0995% CI: [-3.26, 0.34]Wilcoxon (Mann-Whitney)
Secondary
Parent's or Legal Guardian's Perception of Treatment
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Before Treatment | Parent's or Legal Guardian's Perception of Treatment | Very useful | 15 Participants |
| Before Treatment | Parent's or Legal Guardian's Perception of Treatment | useful | 9 Participants |
| Before Treatment | Parent's or Legal Guardian's Perception of Treatment | not at all useful | 0 Participants |
| Before Treatment | Parent's or Legal Guardian's Perception of Treatment | neither useful or not useful | 0 Participants |
| Before Treatment | Parent's or Legal Guardian's Perception of Treatment | not useful | 0 Participants |
Secondary
Participant's Perception of Treatment
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
Population: Applied to all participants aged 10-15 years who were able to communicate their views.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Before Treatment | Participant's Perception of Treatment | Useful | 11 Participants |
| Before Treatment | Participant's Perception of Treatment | Not useful | 0 Participants |
| Before Treatment | Participant's Perception of Treatment | I don't know | 0 Participants |
Secondary
Peak Expiratory Flow (PEF)
Peak expiratory flow percentage of predicted
Time frame: Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Before Treatment | Peak Expiratory Flow (PEF) | 43.5 percentage of predicted |
| After Treatment | Peak Expiratory Flow (PEF) | 47 percentage of predicted |
Secondary
Score on the Ease of Airway Clearance From Parents or Legal Guardians
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Treatment | Score on the Ease of Airway Clearance From Parents or Legal Guardians | 4.21 score on a scale |
| After Treatment | Score on the Ease of Airway Clearance From Parents or Legal Guardians | 2.13 score on a scale |
p-value: <0.00195% CI: [-2.5, -2]Wilcoxon (Mann-Whitney)
Secondary
Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Before Treatment | Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants | 6.45 score on a scale |
| After Treatment | Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants | 2 score on a scale |
p-value: 0.00395% CI: [-5.5, -3]Wilcoxon (Mann-Whitney)
Secondary
%SpO2
Nocturnal oxygen saturation
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 21/24 patients had complete records for this outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Treatment | %SpO2 | 96.55 percentage of SpO2 | Standard Deviation 1.92 |
| After Treatment | %SpO2 | 96.53 percentage of SpO2 | Standard Deviation 1.83 |
p-value: 0.9795% CI: [-0.69, 0.76]Wilcoxon (Mann-Whitney)
Secondary
TcPCO2
Nocturnal Transcutaneous Carbon Dioxide in kPa
Time frame: Change from baseline (before treatment) and 12 months after treatment
Population: 21/24 patients had complete records for this outcome
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Before Treatment | TcPCO2 | 5.77 Kilopascal (kPa) | Standard Deviation 0.95 |
| After Treatment | TcPCO2 | 6.00 Kilopascal (kPa) | Standard Deviation 1.04 |
p-value: 0.6595% CI: [-0.38, 0.38]Wilcoxon (Mann-Whitney)