Nebulised 3% Hypertonic Saline Versus 0.9% Saline for Treating Patients Hospitalized With Acute Bronchiolitis

Study Overview
=================
Brief Summary
-----------------
Bronchiolitis is an acute viral infection of the lower respiratory tract. It is most commonly caused by respiratory syncytial virus (RSV). Only supportive therapy, including suctioning nasal secretions, water-electrolyte balance maintenance, and oxygen supplementation when needed, is recommended. The inhalation of 3% hypertonic saline is not recommended in bronchiolitis management. However, a recently published meta-analysis revealed that the inhalation of hypertonic saline can reduce the risk of hospitalisation for outpatients with bronchiolitis, while resulting in a shorter length of hospital stay and reduced severity of respiratory distress for inpatients, although the evidence is of low certainty. The aim of the study is to assess the efficacy of nebulised hypertonic saline for the treatment of children hospitalised with bronchiolitis.

Official Title
-----------------
Nebulised 3% Hypertonic Saline Versus 0.9% Saline for Treating Patients Hospitalized With Acute Bronchiolitis: Protocol of a Randomized, Double-blind, Multicentre Trial

Conditions
-----------------
Bronchiolitis

Intervention / Treatment
-----------------
* Drug: Hypertonic saline
* Drug: Normal saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Children admitted to the hospital with the clinical diagnosis of acute bronchiolitis, which is defined as an apparent viral respiratory tract infection associated with airway obstruction manifested by at least one of following symptoms: Tachypnoea (WHO definition). Increased respiratory effort manifested as follows: Nasal flaring; Grunting; Use of accessory muscles; Intercostal and/or subcostal chest wall retractions; Apnoe. Crackles and/or wheezing. Aged 5 weeks - 24 months old. A caregiver must provide written informed consent. Exclusion Criteria: Infants hospitalised with severe bronchiolitis (requiring mechanical ventilation or intensive care, or oxygen saturation < 85% on room air). History of prematurity (gestational age <34 weeks). Diagnosis of a clinically significant chronic disease (cardiac, respiratory, neuromuscular, or metabolic). Immunodeficiency. Gastro-oesophageal reflux. Diagnosis or suspicion of asthma. Inhaling a nebulised 3% hypertonic saline solution within 12 hours before enrolment. Inhaling bronchodilators within 24 hours before enrolment. Inhaling steroids within 24 hours before enrolment. Systemic steroid therapy in the preceding 2 weeks.

Ages Eligible for Study
-----------------
Minimum Age: 5 Weeks
Maximum Age: 24 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomization will occur within 24 hours of admission
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hypertonic saline<br>3% hypertonic saline (NEBU-dose hypertonic). The treatment will be delivered through nebulisation using oxygen with 5 litres of O2 flow, or through a compressed air-driven jet nebuliser, every 6 hours for three times daily with a night break, until discharge. | Drug: Hypertonic saline<br>* Nebulised 3% hypertonic saline (NEBU-dose hypertonic). Nebulisation will be performed by trained study nurses or by parents under the supervision of a nurse<br>|
| Placebo Comparator: Normal saline<br>0,9% normal saline (NEBU-dose isotonic).The treatment will be delivered through nebulisation using oxygen with 5 litres of O2 flow, or through a compressed air-driven jet nebuliser, every 6 hours for three times daily with a night break, until discharge. | Drug: Normal saline<br>* 0,9% normal saline (NEBU-dose isotonic). Nebulisation will be performed by trained study nurses or by parents under the supervision of a nurse<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of hospital stay (LOS). |  | From admission to hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants requiring oxygen supplementation |  | During the intervention | 
| Duration of oxygen supplementation | among those requiring oxygen | During the intervention | 
| The time until the infant will be assessed as being 'fit for discharge' | which is defined as the point at which the infant will be feeding adequately (taking >75% of their usual intake based on parents' assessment) and will have a saturation of at least 92% for 6 h on room air, while the axillary body temperature will remain - among those requiring oxygen | During the intervention | 
| Number of participants requiring hospital readmission after discharge |  | 7 days after the end of interventions | 
| Number of adverse events | especially incidence of acute otitis media and pneumonia | 7 days after the end of interventions | 
| Worsening of clinical status, including the following: | PICU admission The need for oxygen supplementation via HNFC; Bronchospasm within 30 minutes of a nebulised study treatment as indicated by an increase/worsening of the RDAI of <4 points. | During the intervention | 
| Value of clinical severity score (RDAI and Wang Scale) | 30 minutes after intervention and 24 h, 48 h, and 72 h after enrolment | During the intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
hypertonic saline, infants, RCT