Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study

NCT ID: NCT03567473

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 864 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-13
• Study Completion Date: 2025-05-21

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active Intervention Arm

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

Group Type: EXPERIMENTAL

Oral dexamethasone

Intervention Type: 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

Nebulized Epinephrine

Intervention Type: DRUG

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

MDI Epinephrine

Intervention Type: 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.

Control Arm

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.

Group Type: PLACEBO_COMPARATOR

Oral placebo

Intervention Type: 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.

Nebulized normal saline

Intervention Type: DRUG

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

MDI placebo

Intervention Type: DRUG

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

Interventions

Oral dexamethasone

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

Intervention Type: DRUG

Nebulized Epinephrine

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

Intervention Type: DRUG

Oral placebo

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.

Intervention Type: DRUG

Nebulized normal saline

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

Intervention Type: DRUG

MDI Epinephrine

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.

Intervention Type: DRUG

MDI placebo

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

Intervention Type: DRUG

Other Intervention Names

Dexamethasone; Nebulized Adrenaline; Placebo; Saline; MDI Adrenaline; Placebo

Eligibility Criteria

Inclusion Criteria

1. 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.

2. 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.

Exclusion Criteria

1. 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.

2. 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.

3. 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.

4. Presenting with symptoms of apnea prior to enrollment.

5. Treatment with oral, inhaled, or IV corticosteroids within the last 1 week.

6. History of adverse reaction to glucocorticoids.

7. Treatment with any beta-agonists (salbutamol/albuterol or epinephrine/adrenaline) in the ED prior to study enrolment.

8. 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.

9. Insurmountable language barrier (patient's parent/guardian is unable to understand English or French to give informed consent and participate in follow-up).

10. 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.

11. Previous enrolment in the trial.

12. Unavailability for follow-up period.

13. Certain admission to hospital.

• Minimum Eligible Age: 60 Days
• Maximum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Children's Hospital Research Institute of Manitoba

OTHER

Sponsor Role: collaborator

Research Manitoba

OTHER

Sponsor Role: collaborator

Women and Children's Health Research Institute, University of Alberta

UNKNOWN

Sponsor Role: collaborator

Alberta Children's Hospital Research Institute

OTHER

Sponsor Role: collaborator

The Hospital for Sick Children

OTHER

Sponsor Role: collaborator

Department of Pediatrics, Western University

UNKNOWN

Sponsor Role: collaborator

St. Justine's Hospital

OTHER

Sponsor Role: collaborator

Children's Hospital of Eastern Ontario

OTHER

Sponsor Role: lead

Responsible Party

Amy Plint

MD, MSc, FRCPC, Research Chair in Pediatric Emergency Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Amy Plint, MSc, MD

Role: PRINCIPAL_INVESTIGATOR

Childrens Hospital of Eastern Ontario (CHEO)

Locations

Women and Children's Hospital

Adelaide, , Australia

Monash Medical Centre

Melbourne, , Australia

Perth Children's Hospital

Perth, , Australia

Children's Hospital of Alberta

Calgary, Alberta, Canada

Stollery Children's Hospital

Edmonton, Alberta, Canada

Childrens Hospital at London Health Sciences

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

CHU Sainte-Justines Hospital

Montreal, Quebec, Canada

Children's Hospital of Winnipeg

Sherbrook, Winnipeg, Canada

Starship Children's Hospital

Auckland, , New Zealand

Kidz First Hospital

Auckland, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Countries

Australia; Canada; New Zealand

References

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.

Reference Type: DERIVED

PMID: 35410375 (View on PubMed)

Other Identifiers

CTO 1423

Identifier Type: -

Identifier Source: org_study_id