Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study

NCT03567473 | Completed Phase 3 DMC

• 1 other identifier: CTO 1423
• Study Type: interventional
• Target: 864
• Locations: 3 countries
• Sites: 12

Brief Summary

We hypothesize that infants with bronchiolitis treated with inhaled epinephrine in the Emergency Department (ED) and a 2-day course of oral dexamethasone will have fewer hospitalizations over 7 days compared to infants treated with placebo. To examine this hypothesis, we will conduct a phase III, multicentre, randomized, double-blind trial. Infants presenting to one of twelve study EDs will be enrolled to one of two study groups: (1) inhaled epinephrine and oral dexamethasone or (2) inhaled placebo and oral placebo. Our primary outcome will be admission for bronchiolitis by day 7 following the enrolment. As a planned secondary analysis, a between-group comparison of the primary outcome will be performed in those patients presenting with a first episode of bronchiolitis.

Conditions

Bronchiolitis

Outcome Measures

Primary Outcomes (1)

• Admission to hospital for bronchiolitis within 7 days post enrollment

  1\) patient being admitted to inpatient ward, or 2) an ED length of stay 12 hours or greater or 3) a combined ED and observation unit stay of 12 hours or greater.

  7 days post enrollment

Secondary Outcomes (4)

• Admission to hospital for bronchiolitis at the time of the enrollment ED visit

  Enrollment visit

• All cause admission to Hospital within 21 days following enrollment ED visit

  up to 21 days post enrollment

• All cause Health care provider visits (including ED visits) by day 21 following enrollment ED

  up to 21 days post enrollment

• Health Care related costs within the 21 days following enrollment ED visits.

  up to 21 days post enrollment

Other Outcomes (14)

• Safety outcome 1: Gastrointestinal bleeding

  up to 21 days post enrollment

• Safety outcome 2: Serious Bacterial Infection

  up to 21 days post enrollment

• Safety outcome 3: Severe Varicella

  up to 21 days post enrollment

Study Arms (2)

Active Intervention Arm

EXPERIMENTAL

Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI

Drug: Oral dexamethasone; Drug: Nebulized Epinephrine; Drug: MDI Epinephrine

Control Arm

PLACEBO COMPARATOR

Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and nebulized saline. OR Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and inhaled placebo given by MDI.

Drug: Oral placebo; Drug: Nebulized normal saline; Drug: MDI placebo

Interventions

Oral dexamethasone DRUG

Two doses of oral dexamethasone, 0.6 mg/kg (maximum single dose 10 mg). One at the time of emergency department enrolment immediately prior to first nebulized treatment and one at approximately 24 hour later

Also known as: Dexamethasone

Active Intervention Arm

Nebulized Epinephrine DRUG

Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment

Also known as: Nebulized Adrenaline

Active Intervention Arm

Oral placebo DRUG

Two doses of oral placebo, 0.6 mL/kg (maximum single dose 10 mL). One at the time of emergency department enrolment immediately prior to nebulized treatment and one at approximately 24 hour later . Oral placebo at Canadian sites is composed of OraBlendTM and in New Zealand and Australian sites will be a compounded solution.

Also known as: Placebo

Control Arm

Nebulized normal saline DRUG

Two nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment

Also known as: Saline

Control Arm

MDI Epinephrine DRUG

Two doses of Epinephrine given by MDI plus spacer at 625 mcg (5 actuations of 125mcg) 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment.

Also known as: MDI Adrenaline

Active Intervention Arm

MDI placebo DRUG

Two doses of inhaled placebo given by MDI plus spacer, 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment.

Also known as: Placebo

Control Arm

Eligibility Criteria

• Age: 60 Days - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Presenting to the ED with an episode of bronchiolitis. Bronchiolitis will be defined as an episode of wheezing or crackles in a child \< 12 month of age associated with signs of an upper respiratory tract infection (e.g. cough, coryza, nasal congestion) during the period deemed to be peak season for RSV bronchiolitis (approximately December to April in Northern Hemisphere and June to October in Southern Hemisphere). We have chosen not to define bronchiolitis as the first episode of wheezing or crackles to better reflect the clinical guidelines and clinical practice internationally.
• \*Adjustment for COVID-19: The COVID-19 pandemic has resulted in unseasonal RSV and bronchiolitis seasons. As such, adjustments will be made to study recruitment to ensure recruitment occurs during peak RSV times. In order to achieve this aim, the study may in some sites recruit for 12 months of the year.
• Age 60 days to less than 12 months. Children younger than 60 days will not be enrolled due to the risk of concomitant infection and other issues pertaining to glucocorticoid use in the very young. Children older than 12 months will not be enrolled to minimize the risk of enrolling children with asthma.

You may not qualify if:

• Respiratory distress assessment instrument (RDAI) score of less than or equal to 3. This RDAI will ensure children with very mild respiratory diseases are not enrolled. This is the lower limit of the RDAI range used in CanBEST.
• Previously known chronic disease that may affect cardiopulmonary status of the patient, such as bronchopulmonary dysplasia currently receiving oxygen, cystic fibrosis, congenital heart disease and immune deficiency. These children may be at higher risk for developing severe illness.
• Severe respiratory distress evidenced by a sustained pulse rate \> 200 beats/min, a sustained respiratory rate \> 80 breaths/min, profound lethargy (as deemed by the treating physician), or requiring resuscitation room care. We will exclude these children as they are likely to be admitted due to severity of illness.
• Presenting with symptoms of apnea prior to enrollment.
• Treatment with oral, inhaled, or IV corticosteroids within the last 1 week.
• History of adverse reaction to glucocorticoids.
• Treatment with any beta-agonists (salbutamol/albuterol or epinephrine/adrenaline) in the ED prior to study enrolment.
• Presence of varicella or recent (less than 3 weeks) close contact (defined as any household or daycare contact, or greater than 15 minutes of face to face contact, or greater than 1 hour of being in the same dwelling with an individual) without a history of prior infection. These patients are not enrolled to reduce any risk of developing severe varicella with corticosteroid use.
• Insurmountable language barrier (patient's parent/guardian is unable to understand English or French to give informed consent and participate in follow-up).
• Any child born at less than 37weeks gestation who is younger than 60 days corrected age. We will not enroll these children to lower any risk of exposing young infants to corticosteroids.
• Previous enrolment in the trial.
• Unavailability for follow-up period.
• Certain admission to hospital.

Sponsors & Collaborators

• Children's Hospital of Eastern Ontario: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Children's Hospital Research Institute of Manitoba: collaborator
• Research Manitoba: collaborator
• Women and Children's Health Research Institute, University of Alberta: collaborator
• Alberta Children's Hospital Research Institute: collaborator
• The Hospital for Sick Children: collaborator
• Department of Pediatrics, Western University: collaborator
• St. Justine's Hospital: collaborator

Study Sites (12)

Women and Children's Hospital

Adelaide, 5006, Australia

Location

Monash Medical Centre

Melbourne, 3168, Australia

Location

Perth Children's Hospital

Perth, 6008, Australia

Location

Children's Hospital of Alberta

Calgary, Alberta, T3B 6A9, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, T6G 2C8, Canada

Location

Childrens Hospital at London Health Sciences

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

CHU Sainte-Justines Hospital

Montreal, Quebec, HT3 1C5, Canada

Location

Children's Hospital of Winnipeg

Sherbrook, Winnipeg, R3A 1S1, Canada

Location

Starship Children's Hospital

Auckland, 1142, New Zealand

Location

Kidz First Hospital

Auckland, 2025, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

Related Publications (2)

• Heath A, Rios D, Vogel KI, Rowe T, Wills-Ibarra N, Oakley E, Offringa M, Pechlivanoglou P, Klassen TP, Dalziel SR, Plint AC; KidsCan Pediatric Emergency Research Canada (PERC) Innovative Pediatric Clinical Trials and Pediatric Research in Emergency Department International Collaborative (PREDICT) BIPED Study Team. A randomised controlled trial comparing epinephrine and dexamethasone to placebo in the treatment of infants with bronchiolitis (BIPED study): a statistical analysis plan. Trials. 2025 Nov 12;26(1):496. doi: 10.1186/s13063-025-09125-w.

  PMID: 41225556 DERIVED

• Lan J, Plint AC, Dalziel SR, Klassen TP, Offringa M, Heath A; Pediatric Emergency Research Canada (PERC) KIDSCAN/PREDICT BIPED Study Group. Remote, real-time expert elicitation to determine the prior probability distribution for Bayesian sample size determination in international randomised controlled trials: Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone (BIPED) study. Trials. 2022 Apr 11;23(1):279. doi: 10.1186/s13063-022-06240-w.

  PMID: 35410375 DERIVED

MeSH Terms

Conditions

Bronchiolitis

Interventions

Dexamethasone; Sodium Chloride

Condition Hierarchy (Ancestors)

Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Amy Plint, MSc, MD

  Childrens Hospital of Eastern Ontario (CHEO)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study personnel (including study nurses, coordinators, investigators, data management staff, and statistical team), health care staff providing patient care, and patients/families will be blinded to the study group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, MSc, FRCPC, Research Chair in Pediatric Emergency Medicine

Study Record Dates

• First Submitted: June 13, 2018
• First Posted: June 25, 2018
• Study Start: December 13, 2018
• Primary Completion: January 7, 2025
• Study Completion: May 21, 2025
• Last Updated: July 28, 2025

Record last verified: 2025-07

Locations

CA (6); NZ (3); AU (3)