Isotonic Saline for Children With Bronchiolitis

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Asthma in Children; Bronchiolitis; Respiratory Disease; Acute Respiratory Infection; Viral Infection
• Intervention / Treatment: Other: Nebulized isotonic saline; Other: Nasal irrigation with isotonic saline

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ann-Marie M Schoos, MD, PhD; Phone Number: +45 20681250; Email: annms@regionsjaelland.dk
• Study Contact Backup: Name: Maren J Rytter, MD, PhD; Email: mjry@regionsjaelland.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nebulized isotonic saline; 5 ml of isotonic saline is administered through a nebulizer with a flow of 10 l oxygen/min	Other: Nebulized isotonic saline; The intervention will constitute nebulized isotonic saline.
Experimental: Nasal irrigation with isotonic saline; 0.5-2 ml isotonic saline in each nostril administered as nasal drops	Other: Nasal irrigation with isotonic saline; The intervention will constitute isotonic saline administered as nasal drops.
No Intervention: No treatment with saline; These children will not receive any treatment with isotonic saline, but superficial suctioning of nasal secretions as needed (as part of standard care).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of hospitalization	In hours	0-7 days typically (max 14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Number of participants being readmitted after discharge	If readmitted to the hospital	30 days after discharge
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)
Number of participants needing oxygen therapy	Need for oxygen therapy	During admission (up to day 14)
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)
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
Fluid supplements	Requirement of fluid supplements either by nasogastric tube or intravenous	During admission (up to day 14)
pCO2	Highest pCO2 measured	During admission (up to day 14)
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)
Number of participants with visible distress	Visible distress in the child during delivery of treatment	During admission (up to day 14)
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

Collaborators and Investigators

• Sponsor: Slagelse Hospital
• Collaborators: Zealand University Hospital; Copenhagen University Hospital at Herlev; Holbaek Sygehus; Copenhagen University Hospital, Hvidovre; Nordsjaellands Hospital; Nykøbing Falster Hospital
• Investigators: Principal Investigator: Ann-Marie M Schoos, MD, PhD, Slagelse Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2029

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: June 13, 2023
• First Posted (Actual): June 15, 2023

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Nasal saline irrigation; Nebulized saline; Nasal saline drops; Respiratory severity score
• Additional Relevant MeSH Terms: Pathologic Processes; Lung Diseases; Disease Attributes; Bronchial Diseases; Lung Diseases, Obstructive; Bronchitis; Infections; Communicable Diseases; Virus Diseases; Respiratory Tract Infections; Bronchiolitis; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: Bronchiolitis project

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We have planned to share all IPD with other researchers upon request.
• IPD Sharing Time Frame: We have planned to share all IPD with other researchers upon request 5 years after publication.
• IPD Sharing Access Criteria: Researchers who request access.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No