Isotonic Saline for Children With Bronchiolitis

Asthma in Children Clinical Trial

Official title:

Isotonic Saline for Children With Bronchiolitis - a Randomized Controlled Non-inferiority Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05902702
• Other study ID #: Bronchiolitis project
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 2023
• Est. completion date: September 2029

Study information

• Verified date: June 2023
• Source: Slagelse Hospital
• Contact: Ann-Marie M Schoos, MD, PhD
• Phone: +45 20681250
• Email: annms[@]regionsjaelland.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this randomized clinical trial is to investigate the optimal supportive treatment of bronchiolitis in infants from 0-12 months of age. The main question[s] it aims to answer are:

• To investigate whether isotonic saline should be used as supportive treatment for children with bronchiolitis, and if so, identify the optimal route of administration. The primary outcome is duration of hospitalization.

• To investigate the current epidemiology of the viral pathogens causing bronchitis in children in Denmark, and to assess whether children infected with specific pathogens might benefit from treatment with isotonic saline.

The children are randomized after inclusion through computer randomization to one of the 3 arms in the study:

1. Nebulized isotonic saline

2. Nasal irrigation with isotonic saline

3. No treatment with saline

The investigators will compare treatment with saline (both methods) with no treatment, and the investigators will also compare the two methods of delivery of saline (nebulized vs. nasal irrigation).

Description:

Design: An investigator-initiated, multicenter, open label, three-arm randomized, controlled non-inferiority trial.

Study sites: Seven pediatric departments in eastern Denmark (Slagelse Hospital, Holbæk Hospital, Zealand University Hospital Roskilde, Copenhagen University Hospital Hvidovre, Copenhagen University Hospital Herlev, Nordsjaellands Hospital, and Nykoebing Falster Hospital).

Participants: Children aged 0-12 months admitted to a pediatric department or emergency department in eastern Denmark with bronchiolitis, whose parents provide informed consent for participation.

Randomization: Participating children are randomized 1:1:1 through computer randomization to either nebulized isotonic saline, nasal irrigation with isotonic saline or no isotonic saline therapy at all. Participating children will have a nasal sample collected and tested for a panel of viral pathogens. Excess material (1 ml nasal lining fluid) from upper airway respiratory samples will be stored in a research biobank until 31.12.2030 and used for sub-phenotyping of bronchiolitis and for developing personalized treatment and prediction of later asthma by means of host transcriptomics and metabolomics, 16S sequencing of the airway microbiome and meta-transcriptomics.

All other treatment is given according to standard of care guidelines.

Sample size: By including 249 children in total (83 in each arm) the investigators can prove non-inferiority of nasal irrigation or nebulized saline relative to no saline with a non-inferiority limit of 12 hours admission, alpha 2.5% and a power of 80%. The investigators aim to include 300 children in total to account for dropouts.

Recruitment: Children will only be included if both parents provide informed consent.

Perspectives: This study may improve current practice for supportive treatment of children with bronchiolitis. If saline is found to be helpful, it may be implemented into global guidelines. If no effect of saline is found, physicians may stop spending resources and manpower on an ineffective and potentially unpleasant treatment. Second, if saline is effective, but nasal irrigation proves to be non-inferior to nebulization, it may also reduce the workload of nurses, and possibly duration of hospitalization, because the treatment can be delivered by the parents at home. Moreover, the parents are empowered to manage their child's illness themselves, potentially improving the experience of parents as well as the affected child.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: September 2029
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 12 Months

Eligibility

Inclusion Criteria:

• Children aged 0-12 months, whose parents give informed consent to participate, with symptoms of bronchiolitis including at least one of:

• Runny nose

• Dry and persistent cough

• Labored breathing (tachypnea, retractions, nasal flaring)

• Grunting

• Cyanosis or apnea

• Wheezing or crackles on auscultation

• O2 saturations below 92 %

• Difficulties feeding

Exclusion Criteria:

• Children with cystic fibrosis or other serious congenital lung diseases

• Children in whom treatment with short-acting beta-2 agonist is initiated (as this is delivered in nebulized isotonic saline).

Related Conditions & MeSH terms

• Acute Respiratory Infection
• Asthma in Children
• Bronchiolitis
• Communicable Diseases
• Infections
• Respiration Disorders
• Respiratory Disease
• Respiratory Tract Diseases
• Respiratory Tract Infections
• Viral Infection
• Virus Diseases

Intervention

Other:
• Nebulized isotonic saline
The intervention will constitute nebulized isotonic saline.
• Nasal irrigation with isotonic saline
The intervention will constitute isotonic saline administered as nasal drops.

Locations

Country	Name	City	State
n/a

Sponsors (7)

Lead Sponsor	Collaborator
Slagelse Hospital	Copenhagen University Hospital at Herlev, Copenhagen University Hospital, Hvidovre, Holbaek Sygehus, Nordsjaellands Hospital, Nykøbing Falster Hospital, Zealand University Hospital

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of hospitalization	In hours	0-7 days typically (max 14 days)
Secondary	Number of participants needing respiratory support	The need for respiratory support with nasal continuous positive airway pressure or high-flow oxygen therapy.	During admission (up to day 14)
Secondary	Number of participants being readmitted after discharge	If readmitted to the hospital	30 days after discharge
Secondary	Respiratory severity score	Respiratory Severity Score with Heart Rate (RSS-HR), scale from 0-12, higher score means worse outcome.	During admission (up to day 14)
Secondary	Number of participants needing oxygen therapy	Need for oxygen therapy	During admission (up to day 14)
Secondary	Number of participants needing transfer to ICU or SICU	Transfer to the intensive care unit or semi-intensive care unit	During admission (up to day 14)
Secondary	Health-related Quality of Life	Health-related Quality of Life questionnaire developed by Díez-Gandía et al. (PMID: 34488668) including 12 items. Item responses will be scored using the following algorithm (unweighted method): (1) Each response item will be assigned a value according to its gravity (1 = best level or 9 = worst level). (2) The sum of the scores will be standardized using the min-max normalization to a 0-1-point scale, with 1 indicating the best quality of life and 0 the worst.	Up to one month after discharge
Secondary	Fluid supplements	Requirement of fluid supplements either by nasogastric tube or intravenous	During admission (up to day 14)
Secondary	pCO2	Highest pCO2 measured	During admission (up to day 14)
Secondary	Number of participants needing to switch treatment	Clinician-initiated switch to the opposite treatment from the one they were randomized to	During admission (up to day 14)
Secondary	Number of participants with visible distress	Visible distress in the child during delivery of treatment	During admission (up to day 14)
Secondary	Parents satisfaction	Parents satisfaction with the given treatment, questionnaire developed by the investigators exploring satisfaction of 3 items on a scale from 1-10 (total score from 3-30) where higher score means better outcome.	Up to one month after discharge