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

Neuromuscular Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03623698
• Other study ID #: 18IC4403
• Status: Completed
• Start date: June 15, 2018
• Est. completion date: September 26, 2019

Study information

• Verified date: August 2020
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: September 26, 2019
• Est. primary completion date: August 14, 2019
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cerebral Palsy
• Neuromuscular Diseases

Intervention

Drug:
• Nebulised hypertonic saline
Nebulised hypertonic saline used for a period of at least 12 months

Locations

Country	Name	City	State
United Kingdom	Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. — View Citation

Boitano LJ. Management of airway clearance in neuromuscular disease. Respir Care. 2006 Aug;51(8):913-22; discussion 922-4. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Antibiotic Courses	Treatments due to respiratory exacerbations	Change from baseline (before treatment) and 12 months after treatment
Primary	Number of Hospitalsations Due to Respiratory Exacerbations	Number of respiratory exacerbations that required not planned hospitalisation	Change from baseline (before treatment) and 12 months after treatment
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".	At 12 months after starting treatment with hypertonic saline
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.	At 12 months after starting treatment with hypertonic saline
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.	Change from baseline (before treatment) and 12 months after treatment
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.	Change from baseline (before treatment) and 12 months after treatment
Secondary	Apnea Index (AI)	The number of apneas recorded during the study per hour of sleep	Change from baseline (before treatment) and 12 months after treatment
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.	Change from baseline (before treatment) and 12 months after treatment
Secondary	%SpO2	Nocturnal oxygen saturation	Change from baseline (before treatment) and 12 months after treatment
Secondary	Nocturnal ODI	Oxygen desaturation index: Number of desaturations per hour of sleep	Change from baseline (before treatment) and 12 months after treatment
Secondary	TcPCO2	Nocturnal Transcutaneous Carbon Dioxide in kPa	Change from baseline (before treatment) and 12 months after treatment
Secondary	FEV1/FVC %Predicted Rate of Decline	Rate of decline per year of Tiffenau index	Change from baseline (before treatment) and 12 months after treatment
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	Change from the baseline (before treatment) and 12 months after treatment
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	Change from baseline (before treatment) and 12 months after treatment
Secondary	Peak Expiratory Flow (PEF)	Peak expiratory flow percentage of predicted	Change from baseline peak expiratory flow at 12 months after starting treatment with hypertonic saline