Background: Bronchiolitis exerts a significant burden of illness on infants worldwide predominantly due to need for hospitalization. Currently only supportive care is advised by national guidelines for infants with bronchiolitis. There is evidence that treating infants with bronchiolitis with a combination of inhaled epinephrine and dexamethasone may reduce hospital admissions. Synergy between beta-agonists and corticosteroids is recognized in asthma management and basic science literature demonstrates that co-administration of these medications enhances each other’s effectiveness.  Objective: To determine if infants with bronchiolitis treated with inhaled epinephrine (delivered by metered dose inhaler with spacer or nebulizer) in the emergency department and a 2-day course of oral dexamethasone have fewer hospitalizations (due to bronchiolitis) over 7 days compared to infants treated with placebo. Design: The BIPED study (Bronchiolitis in Infants Epinephrine versus Dexamethasone and Placebo) is a randomized, placebo-controlled, observer, investigator, clinician, and patient blinded superiority clinical trial being conducted in 12 emergency departments across three countries (Canada, New Zealand, and Australia). We will recruit 864 infants between 60 days and 12 months of age with bronchiolitis to receive either (1) two inhaled epinephrine treatments (3 mg via nebulizer or 625 mcg via metered dose inhaler with spacer) 30 minutes apart and a simultaneous dose of oral dexamethasone (0.6 mg/kg, maximum 10 mg) in the emergency department with the dexamethasone repeated at 24 hours or (2) inhaled placebo and oral placebo. The primary outcome is hospital admission for bronchiolitis within 7 days (168 hours) of enrolment. Secondary outcomes include hospital admission during enrolment, and all cause hospital admissions and healthcare provider visits within 21 days of enrolment. We will use a Bayesian approach for data analysis and inference.  Discussion: Given the healthcare burden of bronchiolitis, there is urgent need for a trial to confirm if combination therapy with epinephrine and dexamethasone is effective. Trial registration: ClinicalTrials.gov: NCT03567473.  Registered on 2018-06-13. Protocol version: CTO 1423, dated 20 January 2023 Sponsor-Investigator: Dr. Amy C Plint, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada Secondary Sponsor: Children’s Hospital of Eastern Ontario Research Institute, Ottawa, Ontario, Canada

The authors have declared no competing interest.

ClinicalTrials.gov: NCT03567473

This study was funded by the following. Canadian Institutes of Health Research. National Health Medical Research Council. Perth Childrens Hospital Foundation. Telethon Perth Childrens Hospital Research Fund. Starship Foundation. Cure Kids New Zealand. Childrens Hospital Research Institute of Manitoba and Research Manitoba. Women and Childrens Health Research Institute. Alberta Childrens Hospital Research Institute. Childrens Hospital of Eastern Ontario Research Institute. Hospital for Sick Children Research Institute. Department of Pediatrics at the University of Western Ontario. Centre Hospitalier Universitaire Ste Justine. ACP is supported by a University of Ottawa Research Chair. AH and TPK are supported Canada Research Chairs. SRD is supported by the Cure Kids Chair of Child Health Research.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of Centre Hospitalier Universitaire Sainte-Justine gave ethical approval for this work. Ethics committee of the Childrens Hospital of Eastern Ontario gave ethical approval for this work. Ethics committee of the University of Manitoba (Biomedical Research Board) gave ethical approval for this work. Ethics committee of the University of Alberta gave ethical approval for this study. Ethics committee of the University of Calgary gave ethical approval for this work. The Health and Disability Ethics Committee of New Zealand gave ethic approval for this study. The Child and Adolescent Health Services Human Research Ethics Committee of Australia gave ethical approval for this study.

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De-identified data from this study may be requested by other researchers 2 years after the publication of the primary manuscript by contacting the principal investigator (ACP). Consent for this data sharing will be obtained at the time of consent to enrolment in the trial. Researchers that wish to study the data must have the new study approved by a research ethics board and sign an agreement ensuring confidentiality and restricting data use only to the approved study.