Trial Outcomes & Findings for Nebulised Hypertonic Saline in Children and Young People With Neuromuscular Disease and Cerebral Palsy (NCT NCT03623698)

NCT ID: NCT03623698

Last Updated: 2020-09-16

Results Overview

Treatments due to respiratory exacerbations

• Recruitment status: COMPLETED
• Target enrollment: 24 participants
• Primary outcome timeframe: Change from baseline (before treatment) and 12 months after treatment
• Results posted on: 2020-09-16

Participant Flow

Participant milestones

Measure	Children and Young People With Neuromuscular Disease 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.
Overall Study STARTED	24
Overall Study COMPLETED	24
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Children and Young People With Neuromuscular Disease n=24 Participants Children and young people with neuromuscular disease before nebulised saline was prescribed to them.
Age, Continuous	11 years STANDARD_DEVIATION 4.7 • n=24 Participants
Sex: Female, Male Female	11 Participants n=24 Participants
Sex: Female, Male Male	13 Participants n=24 Participants
Region of Enrollment United Kingdom	24 Participants n=24 Participants
Diagnosis SMA	14 Participants n=24 Participants
Diagnosis Chromosomal myopathy	1 Participants n=24 Participants
Diagnosis Myotubular myopathy	2 Participants n=24 Participants
Diagnosis Nemaline Rod myopathy	1 Participants n=24 Participants
Diagnosis Congenital muscular dystrophy	2 Participants n=24 Participants
Diagnosis LGMD	1 Participants n=24 Participants
Diagnosis Joubert syndrome	1 Participants n=24 Participants
Diagnosis Muscle eye brain disease	1 Participants n=24 Participants
Diagnosis Rett syndrome	1 Participants n=24 Participants
Other characteristics Non-ambulant	21 Participants n=24 Participants
Other characteristics Tracheotomised	3 Participants n=24 Participants
Other characteristics Gastrostomy feeding	17 Participants n=24 Participants
Other characteristics Scoliosis	13 Participants n=24 Participants
Other treatments and medical procedures Antibiotic prophylaxus	12 Participants n=24 Participants
Other treatments and medical procedures Dornase alpha	5 Participants n=24 Participants
Other treatments and medical procedures Home mechanical ventilation	16 Participants n=24 Participants
Other treatments and medical procedures Mechanically assisted cough	14 Participants n=24 Participants
Tonicity of nebulised prescribed Hypertonic saline only (3%, 6%, 7%)	9 Participants n=24 Participants
Tonicity of nebulised prescribed Isotonic saline only (0.9%)	4 Participants n=24 Participants
Tonicity of nebulised prescribed Combination of hypertonic and isotonic saline	11 Participants n=24 Participants

PRIMARY outcome

Timeframe: 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

Treatments due to respiratory exacerbations

Outcome measures

Measure	Before Treatment n=22 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=22 Participants 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%)
Change in Antibiotic Courses Total courses of antibiotics	4 Courses of antibiotics Interval 2.0 to 6.0	1 Courses of antibiotics Interval 0.0 to 2.0
Change in Antibiotic Courses Courses of Oral antibiotics	2.50 Courses of antibiotics Interval 1.0 to 6.0	1.00 Courses of antibiotics Interval 0.0 to 2.0
Change in Antibiotic Courses Courses of intravenous antibiotics	1.00 Courses of antibiotics Interval 0.0 to 1.0	0.00 Courses of antibiotics Interval 0.0 to 0.0

PRIMARY outcome

Timeframe: 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.

Number of respiratory exacerbations that required not planned hospitalisation

Outcome measures

Measure	Before Treatment n=23 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=23 Participants 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%)
Number of Hospitalsations Due to Respiratory Exacerbations	1 Hospitalisations Interval 0.0 to 2.0	0 Hospitalisations Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Before Treatment n=11 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment 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%)
Participant's Perception of Treatment Useful	11 Participants	—
Participant's Perception of Treatment Not useful	0 Participants	—
Participant's Perception of Treatment I don't know	0 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Before Treatment n=24 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment 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%)
Parent's or Legal Guardian's Perception of Treatment Very useful	15 Participants	—
Parent's or Legal Guardian's Perception of Treatment useful	9 Participants	—
Parent's or Legal Guardian's Perception of Treatment neither useful or not useful	0 Participants	—
Parent's or Legal Guardian's Perception of Treatment not useful	0 Participants	—
Parent's or Legal Guardian's Perception of Treatment not at all useful	0 Participants	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Before Treatment n=11 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=11 Participants 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%)
Score on the Ease of Airway Clearance Pictorial Analogue Scale From Children and Young Adults as Participants	6.45 score on a scale Interval 4.0 to 9.0	2 score on a scale Interval 0.0 to 4.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Before Treatment n=24 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=24 Participants 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%)
Score on the Ease of Airway Clearance From Parents or Legal Guardians	4.21 score on a scale Interval 3.0 to 5.0	2.13 score on a scale Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: Change from baseline (before treatment) and 12 months after treatment

Population: 3/24 patients had records for this outcome

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

Outcome measures

Measure	Before Treatment n=3 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=3 Participants 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%)
Apnea Index (AI)	4.87 Events per hour of sleep Standard Deviation 1.02	0.40 Events per hour of sleep Standard Deviation 0.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Before Treatment n=3 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=4 Participants 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%)
AHI	8.53 Events per hour of sleep Standard Deviation 1.70	1.38 Events per hour of sleep Standard Deviation 0.99

SECONDARY outcome

Timeframe: Change from baseline (before treatment) and 12 months after treatment

Population: 21/24 patients had complete records for this outcome

Nocturnal oxygen saturation

Outcome measures

Measure	Before Treatment n=21 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=21 Participants 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%)
%SpO2	96.55 percentage of SpO2 Standard Deviation 1.92	96.53 percentage of SpO2 Standard Deviation 1.83

SECONDARY outcome

Timeframe: Change from baseline (before treatment) and 12 months after treatment

Population: 21/24 patients had complete records for this outcome

Oxygen desaturation index: Number of desaturations per hour of sleep

Outcome measures

Measure	Before Treatment n=21 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=21 Participants 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%)
Nocturnal ODI	4.26 Events per hour of sleep Standard Deviation 3.42	3.32 Events per hour of sleep Standard Deviation 3.33

SECONDARY outcome

Timeframe: Change from baseline (before treatment) and 12 months after treatment

Population: 21/24 patients had complete records for this outcome

Nocturnal Transcutaneous Carbon Dioxide in kPa

Outcome measures

Measure	Before Treatment n=21 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=21 Participants 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%)
TcPCO2	5.77 Kilopascal (kPa) Standard Deviation 0.95	6.00 Kilopascal (kPa) Standard Deviation 1.04

SECONDARY outcome

Timeframe: Change from baseline (before treatment) and 12 months after treatment

Population: 5/24 patients had complete records for this outcome

Rate of decline per year of Tiffenau index

Outcome measures

Measure	Before Treatment n=5 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=5 Participants 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%)
FEV1/FVC %Predicted Rate of Decline	97.37 percentage of predicted Interval 84.5 to 110.5	98.89 percentage of predicted Interval 92.0 to 109.0

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Before Treatment n=2 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=5 Participants 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%)
FEV1% Predicted Rate of Decline	-8.03 percentage of predicted Interval -8.67 to -8.03	4.00 percentage of predicted Interval -2.14 to 17.55

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Before Treatment n=2 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=3 Participants 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%)
FVC% Predicted Rate of Decline	-7.44 percentage of predicted Interval -9.33 to -7.44	7.00 percentage of predicted Interval -15.43 to 7.0

SECONDARY outcome

Timeframe: Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline

Peak expiratory flow percentage of predicted

Outcome measures

Measure	Before Treatment n=6 Participants Children and young people with neuromuscular disease during the 12 months before being prescribed treatment with nebulised saline	After Treatment n=5 Participants 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%)
Peak Expiratory Flow (PEF)	43.5 percentage of predicted Interval 33.0 to 47.5	47 percentage of predicted Interval 42.0 to 74.0

Adverse Events

Children and Young People With Neuromuscular Disease

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Mrs. Natalia Galaz Souza

Imperial College London

Phone: 07751842851

Email: natalia.galaz-souza16@imperial.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place