Clinical trial NCT05902702: Isotonic Saline for Children With Bronchiolitis
Official title: Isotonic Saline for Children With Bronchiolitis - a Randomized Controlled Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Bronchiolitis
Respiratory Disease
Asthma in Children
Viral Infection
Acute Respiratory Infection
Keywords: Nebulized saline
Nasal saline drops
Nasal saline irrigation
Respiratory severity score
Lead sponsor: Slagelse Hospital
Sponsor class: OTHER
Collaborators: name: Copenhagen University Hospital at Herlev
name: Zealand University Hospital
name: Copenhagen University Hospital, Hvidovre
name: Holbaek Sygehus
name: Nordsjaellands Hospital
name: Nykøbing Falster Hospital
First posted: 2023-06-15
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: An investigator-initiated, multicenter, open label, three-arm randomized, controlled non-inferiority trial.
Primary purpose: SUPPORTIVE_CARE

Brief 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).

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Duration of hospitalization
timeFrame: 0-7 days typically (max 14 days)
Secondary outcomes:
measure: Number of participants needing respiratory support
timeFrame: During admission (up to day 14)
measure: Number of participants being readmitted after discharge
timeFrame: 30 days after discharge
measure: Respiratory severity score
timeFrame: During admission (up to day 14)
measure: Number of participants needing oxygen therapy
timeFrame: During admission (up to day 14)
measure: Number of participants needing transfer to ICU or SICU
timeFrame: During admission (up to day 14)
measure: Health-related Quality of Life
timeFrame: Up to one month after discharge
measure: Fluid supplements
timeFrame: During admission (up to day 14)
measure: pCO2
timeFrame: During admission (up to day 14)
measure: Number of participants needing to switch treatment
timeFrame: During admission (up to day 14)
measure: Number of participants with visible distress
timeFrame: During admission (up to day 14)
measure: Parents satisfaction
timeFrame: Up to one month after discharge
Other outcomes:
Locations:
Study officials:
affiliation: Slagelse Hospital
name: Ann-Marie M Schoos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: