Clinical trial NCT03567473: Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study
Official title: A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Bronchiolitis
Lead sponsor: Children's Hospital of Eastern Ontario
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
name: Children's Hospital Research Institute of Manitoba
name: Research Manitoba
name: Women and Children's Health Research Institute, University of Alberta
name: Alberta Children's Hospital Research Institute
name: The Hospital for Sick Children
name: Department of Pediatrics, Western University
name: St. Justine's Hospital
First posted: 2018-06-25
Enrollment: 864
Sex: ALL
Minimum age (years): 60
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Admission to hospital for bronchiolitis within 7 days post enrollment
timeFrame: 7 days post enrollment
Secondary outcomes:
measure: Admission to hospital for bronchiolitis at the time of the enrollment ED visit
timeFrame: Enrollment visit
measure: All cause admission to Hospital within 21 days following enrollment ED visit
timeFrame: up to 21 days post enrollment
measure: All cause Health care provider visits (including ED visits) by day 21 following enrollment ED
timeFrame: up to 21 days post enrollment
measure: Health Care related costs within the 21 days following enrollment ED visits.
timeFrame: up to 21 days post enrollment
Other outcomes:
measure: Safety outcome 1: Gastrointestinal bleeding
timeFrame: up to 21 days post enrollment
measure: Safety outcome 2: Serious Bacterial Infection
timeFrame: up to 21 days post enrollment
measure: Safety outcome 3: Severe Varicella
timeFrame: up to 21 days post enrollment
measure: Safety outcome 4: Death
timeFrame: up to 21 days post enrollment
measure: Exploratory Outcome 1: Admission to hospital for bronchiolitis within 21 days following enrollment ED visit
timeFrame: up to 21 days post enrollment
measure: Exploratory Outcome 2: Admission to ICU within 21 days following enrollment ED visit for bronchiolitis and requiring intubation or continuous positive airway pressure (CPAP)
timeFrame: up to 21 days post enrollment
measure: Exploratory Outcome 3: All cause admission to hospital with 7 days following enrollment ED visit
timeFrame: up to 7 days post enrollment ED visit
measure: Exploratory Outcome 4: All cause ED visits within 21 days following enrollment ED visit
timeFrame: up to 21 days post enrollment ED
measure: Exploratory Outcome 5: Length of stay for the enrollment ED visit (in hours)
timeFrame: Enrollment ED visit
measure: Exploratory Outcome 6: Length of hospital admission for those patients admitted at their enrollment visit
timeFrame: Admissions at enrollment ED visit
measure: Exploratory Outcome 7: Resolution of symptoms as documented on a standardized questionnaire during the telephone or email at day 7 and 21 days.
timeFrame: up to 21 days post enrollment
measure: Exploratory Outcome 8: Out of pocket expenses
timeFrame: up to 21 days post enrollment
measure: Exploratory Outcome 10: Health care utilization (including ambulatory visits, ED visits, hospitalization) for respiratory illness
timeFrame: Up to 18 years of age
measure: Exploratory Outcome 11: Development of respiratory illnesses
timeFrame: Up to 18 years of age
Locations:
city: Adelaide
country: Australia
facility: Women and Children's Hospital
city: Melbourne
country: Australia
facility: Monash Medical Centre
city: Perth
country: Australia
facility: Perth Children's Hospital
city: Calgary
country: Canada
facility: Children's Hospital of Alberta
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: London
country: Canada
facility: Childrens Hospital at London Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
state: Ontario
city: Montréal
country: Canada
facility: CHU Sainte-Justines Hospital
state: Quebec
city: Sherbrook
country: Canada
facility: Children's Hospital of Winnipeg
state: Winnipeg
city: Auckland
country: New Zealand
facility: Starship Children's Hospital
city: Auckland
country: New Zealand
facility: Kidz First Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
Study officials:
affiliation: Childrens Hospital of Eastern Ontario (CHEO)
name: Amy Plint, MSc, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.