BronchiolitisPhase 3BIPEDNCT03567473
Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study
A Phase 3 study testing Oral dexamethasone, Nebulized Epinephrine and Nebulized normal saline in people with Bronchiolitis, run by Children's Hospital of Eastern Ontario at 12 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 days to 12 months
- Conditions the study is for
- Bronchiolitis
- What is being tested?
- Oral dexamethasone, Nebulized Epinephrine and Nebulized normal saline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 864 participants
- Where
- 12 sitesin 3 countries
- Study dates
- 13 Dec 2018to 21 May 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 days to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 13Show fewer
- 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.
Trial locations and contacts
12 sites in 3 countries.
12 sites in 3 countries
Canada6 sites
Children's Hospital of Alberta
Calgary, Alberta, T3B 6A9
Stollery Children's Hospital
Edmonton, Alberta, T6G 2C8
Childrens Hospital at London Health Sciences
London, Ontario, N6A 5W9
CHU Sainte-Justines Hospital
Montreal, Quebec, HT3 1C5
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1
Children's Hospital of Winnipeg
Sherbrook, Winnipeg, R3A 1S1
Australia3 sites
Women and Children's Hospital
Adelaide, 5006
Monash Medical Centre
Melbourne, 3168
Perth Children's Hospital
Perth, 6008
New Zealand3 sites
Starship Children's Hospital
Auckland, 1142
Kidz First Hospital
Auckland, 2025
Waikato Hospital
Hamilton, 3240
About this study
Official title: A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
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
- Being tested
- Oral dexamethasone, Nebulized Epinephrine, Oral placebo, Nebulized normal saline, MDI Epinephrine
- Medical subject headings
- Bronchiolitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral dexamethasoneDrug
Also called 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
Nebulized EpinephrineDrug
Also called Nebulized Adrenaline
Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
Oral placeboDrug
Also called 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.
Nebulized normal salineDrug
Also called Saline
Two nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
MDI EpinephrineDrug
Also called MDI Adrenaline
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.
MDI placeboDrug
Also called Placebo
Two doses of inhaled placebo given by MDI plus spacer, 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment.
| Study group | Role | What they receive |
|---|---|---|
| Active Intervention Arm | Experimental | Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI Receives: 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. Receives: Drug: Oral placebo; Drug: Nebulized normal saline; Drug: MDI placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Admission to hospital for bronchiolitis within 7 days post enrollment
- 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.
Measured: 7 days post enrollment
Secondary outcomes (4)
Admission to hospital for bronchiolitis at the time of the enrollment ED visit
- 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.
Measured: Enrollment visit
All cause admission to Hospital within 21 days following enrollment ED visit
- 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.
Measured: up to 21 days post enrollment
All cause Health care provider visits (including ED visits) by day 21 following enrollment ED
Visits to ED, other clinic, primary care provider, or any visit to see a nurse or physician following enrollment
Measured: up to 21 days post enrollment
Health Care related costs within the 21 days following enrollment ED visits.
Health care related costs
Measured: up to 21 days post enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2018
- Study start13 Dec 2018
- Primary completion7 Jan 2025
- Study completion21 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for BronchiolitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 864 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Eastern Ontario
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Children's Hospital Research Institute of Manitoba, Research Manitoba, Women and Children's Health Research Institute, Canada, Alberta Children's Hospital Research Institute, The Hospital for Sick Children, Department of Pediatrics, Western University, St. Justine's Hospital
- Responsible party
- Principal investigator, Amy Plint, Children's Hospital of Eastern Ontario
- Investigators
- Amy Plint, MSc, MD, Principal investigator, Childrens Hospital of Eastern Ontario (CHEO)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03567473
- Sponsor's protocol ID
- CTO 1423
- Acronym
- BIPED
- Status last verified
- Jul 2025
- First submitted
- 13 Jun 2018
- Last updated
- 28 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 41225556Lan 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.
PubMed 35410375
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
- ClinicalTrials.gov ID
- NCT03567473
- Acronym / sponsor ID
- BIPED / CTO 1423
- Conditions
- Bronchiolitis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 864 participants (actual)
- Lead sponsor
- Children's Hospital of Eastern OntarioUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Children's Hospital Research Institute of Manitoba, Research Manitoba, Women and Children's Health Research Institute, Canada, Alberta Children's Hospital Research Institute, The Hospital for Sick Children, Department of Pediatrics, Western University, St. Justine's Hospital
- Study start
- 13 Dec 2018 (actual)
- Primary completion
- 7 Jan 2025 (actual)
- Study completion
- 21 May 2025 (actual)
- First posted
- 25 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Intervention Arm | Experimental | Drug: Oral dexamethasone, Drug: Nebulized Epinephrine, Drug: MDI EpinephrineOral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI |
| Control Arm | Placebo comparator | Drug: Oral placebo, Drug: Nebulized normal saline, Drug: MDI placeboOral 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. |
Who may qualify
- Ages
- 60 days to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral dexamethasoneAlso: DexamethasoneTwo 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 | Drug | Active Intervention Arm |
| Nebulized EpinephrineAlso: Nebulized AdrenalineTwo nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment | Drug | Active Intervention Arm |
| Oral placeboAlso: PlaceboTwo 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. | Drug | Control Arm |
| Nebulized normal salineAlso: SalineTwo nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment | Drug | Control Arm |
| MDI EpinephrineAlso: MDI AdrenalineTwo 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. | Drug | Active Intervention Arm |
| MDI placeboAlso: PlaceboTwo doses of inhaled placebo given by MDI plus spacer, 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment. | Drug | Control Arm |
Primary outcome
Admission to hospital for bronchiolitis within 7 days post enrollment
Time frame: 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.
4 secondary outcomes
Admission to hospital for bronchiolitis at the time of the enrollment ED visit
Time frame: Enrollment visit
All cause admission to Hospital within 21 days following enrollment ED visit
Time frame: up to 21 days post enrollment
All cause Health care provider visits (including ED visits) by day 21 following enrollment ED
Time frame: up to 21 days post enrollment
Health Care related costs within the 21 days following enrollment ED visits.
Time frame: up to 21 days post enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2025.
- Derived from this study: PubMed 41225556Heath 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.
- Derived from this study: PubMed 35410375Lan 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy Plint, MSc, MD principal investigator
Childrens Hospital of Eastern Ontario (CHEO)
12 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Oral dexamethasone, Nebulized Epinephrine and Nebulized normal saline in people with Bronchiolitis, run by Children's Hospital of Eastern Ontario at 12 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Canada, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Admission to hospital for bronchiolitis within 7 days post enrollment (time frame: 7 days post enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03567473, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2025.