Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study (BIPED)
Primary Purpose
Bronchiolitis
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Oral dexamethasone
Nebulized Epinephrine
Oral placebo
Nebulized normal saline
MDI Epinephrine
MDI placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bronchiolitis
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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:
- 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.
Sites / Locations
- Women and Children's HospitalRecruiting
- Monash Medical CentreRecruiting
- Perth Children's HospitalRecruiting
- Children's Hospital of AlbertaRecruiting
- Stollery Children's HospitalRecruiting
- Childrens Hospital at London Health SciencesRecruiting
- CHEORecruiting
- CHU Sainte-Justines HospitalRecruiting
- Children's Hospital of WinnipegRecruiting
- Starship Children's HospitalRecruiting
- Kidz First Hospital
- Waikato HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active Intervention Arm
Control Arm
Arm Description
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Admission to hospital for bronchiolitis at the time of the enrollment ED visit
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.
All cause admission to Hospital within 21 days following enrollment ED visit
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.
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
Health Care related costs within the 21 days following enrollment ED visits.
Health care related costs
Full Information
NCT ID
NCT03567473
First Posted
June 13, 2018
Last Updated
October 5, 2023
Sponsor
Children's Hospital of Eastern Ontario
Collaborators
Canadian Institutes of Health Research (CIHR), Children's Hospital Research Institute of Manitoba, Research Manitoba, Women and Children's Health Research Institute, University of Alberta, Alberta Children's Hospital Research Institute, The Hospital for Sick Children, Department of Pediatrics, Western University, St. Justine's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03567473
Brief Title
Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study
Acronym
BIPED
Official Title
A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 13, 2018 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Children's Hospital of Eastern Ontario
Collaborators
Canadian Institutes of Health Research (CIHR), Children's Hospital Research Institute of Manitoba, Research Manitoba, Women and Children's Health Research Institute, University of Alberta, Alberta Children's Hospital Research Institute, The Hospital for Sick Children, Department of Pediatrics, Western University, St. Justine's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiolitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
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.
Allocation
Randomized
Enrollment
864 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active Intervention Arm
Arm Type
Experimental
Arm Description
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Oral dexamethasone
Other Intervention Name(s)
Dexamethasone
Intervention Description
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
Intervention Name(s)
Nebulized Epinephrine
Other Intervention Name(s)
Nebulized Adrenaline
Intervention Description
Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
Intervention Type
Drug
Intervention Name(s)
Oral placebo
Other Intervention Name(s)
Placebo
Intervention Description
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
Intervention Name(s)
Nebulized normal saline
Other Intervention Name(s)
Saline
Intervention Description
Two nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
Intervention Type
Drug
Intervention Name(s)
MDI Epinephrine
Other Intervention Name(s)
MDI Adrenaline
Intervention Description
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
Intervention Name(s)
MDI placebo
Other Intervention Name(s)
Placebo
Intervention Description
Two doses of inhaled placebo given by MDI plus spacer, 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment.
Primary Outcome Measure Information:
Title
Admission to hospital for bronchiolitis within 7 days post enrollment
Description
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.
Time Frame
7 days post enrollment
Secondary Outcome Measure Information:
Title
Admission to hospital for bronchiolitis at the time of the enrollment ED visit
Description
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.
Time Frame
Enrollment visit
Title
All cause admission to Hospital within 21 days following enrollment ED visit
Description
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.
Time Frame
up to 21 days post enrollment
Title
All cause Health care provider visits (including ED visits) by day 21 following enrollment ED
Description
Visits to ED, other clinic, primary care provider, or any visit to see a nurse or physician following enrollment
Time Frame
up to 21 days post enrollment
Title
Health Care related costs within the 21 days following enrollment ED visits.
Description
Health care related costs
Time Frame
up to 21 days post enrollment
Other Pre-specified Outcome Measures:
Title
Safety outcome 1: Gastrointestinal bleeding
Description
involving melena or frank blood per rectum (and not attributable to other causes, as determined by the treating physician)
Time Frame
up to 21 days post enrollment
Title
Safety outcome 2: Serious Bacterial Infection
Description
meningitis, osteomyelitis or septicaemia
Time Frame
up to 21 days post enrollment
Title
Safety outcome 3: Severe Varicella
Description
All of the following including: arthritis, osteomyelitis, symptomatic hepatitis, pancreatitis, cerebritis, pneumonitis, glomerulonephritis, disseminated intravascular coagulation, thrombo-cytopenia, prolonged vesicular rash (<3 weeks), fasciitis, septicaemia, ocular complications, orchitis, myocarditis, intensive care admission and death
Time Frame
up to 21 days post enrollment
Title
Safety outcome 4: Death
Description
Death
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 1: Admission to hospital for bronchiolitis within 21 days following enrollment ED visit
Description
1) Patient 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.
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 2: Admission to ICU within 21 days following enrollment ED visit for bronchiolitis and requiring intubation or continuous positive airway pressure (CPAP)
Description
Physician admitting patient to ICU for bronchiolitis and requiring oxygen or ventilatory support
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 3: All cause admission to hospital with 7 days following enrollment ED visit
Description
1) Patient 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.
Time Frame
up to 7 days post enrollment ED visit
Title
Exploratory Outcome 4: All cause ED visits within 21 days following enrollment ED visit
Description
Visits to the ED after initial enrollment ED visit
Time Frame
up to 21 days post enrollment ED
Title
Exploratory Outcome 5: Length of stay for the enrollment ED visit (in hours)
Description
defined as discharge time minus oral study medication time, for participants discharged at the enrollment ED
Time Frame
Enrollment ED visit
Title
Exploratory Outcome 6: Length of hospital admission for those patients admitted at their enrollment visit
Description
time of hospital discharge minus the time of oral study medication
Time Frame
Admissions at enrollment ED visit
Title
Exploratory Outcome 7: Resolution of symptoms as documented on a standardized questionnaire during the telephone or email at day 7 and 21 days.
Description
cough, noisy breathing, respiratory distress, sleep and ability to feed
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 8: Out of pocket expenses
Description
transportation, days of missed work, missed leisure activities
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 9: Age dependent variation in the efficacy of epinephrine and dexamethasone
Description
to determine if treatment efficacy varies by age
Time Frame
up to 21 days post enrollment
Title
Exploratory Outcome 10: Health care utilization (including ambulatory visits, ED visits, hospitalization) for respiratory illness
Description
future health care utilization
Time Frame
Up to 18 years of age
Title
Exploratory Outcome 11: Development of respiratory illnesses
Description
asthma, wheezing and other respiratory illnesses
Time Frame
Up to 18 years of age
10. Eligibility
Sex
All
Minimum Age & Unit of Time
60 Days
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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:
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kristina I Vogel
Phone
613-737-7600
Ext
3348
Email
kvogel@cheo.on.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Candice McGahern
Phone
613-737-7600
Ext
4111
Email
CMcGahern@cheo.on.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amy Plint, MSc, MD
Organizational Affiliation
Childrens Hospital of Eastern Ontario (CHEO)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Women and Children's Hospital
City
Adelaide
ZIP/Postal Code
5006
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gaby Nivea
Email
gaby.nieva@sa.gov.au
First Name & Middle Initial & Last Name & Degree
Amit Kochar, MD
Facility Name
Monash Medical Centre
City
Melbourne
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Grant
Email
jennifer.grant1@monash.edu
First Name & Middle Initial & Last Name & Degree
Simon Craig, MD
Facility Name
Perth Children's Hospital
City
Perth
ZIP/Postal Code
6008
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharon O'brien
Email
Sharon.O'Brien@health.wa.gov.au
First Name & Middle Initial & Last Name & Degree
Meredith Borland, MD
Facility Name
Children's Hospital of Alberta
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B 6A9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelly Kim
Phone
403-955-5451
Email
kelly.kim@albertahealthservices.ca
First Name & Middle Initial & Last Name & Degree
Graham Thompson, MD
Facility Name
Stollery Children's Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2C8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadia Schular
Phone
587-588-7231
Email
nadiaschular@ualberta.ca
First Name & Middle Initial & Last Name & Degree
Andrew Dixon, MD
Facility Name
Childrens Hospital at London Health Sciences
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Leslie Boisvert
Email
Leslie.Boisvert@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Gary Joubert, MD
Facility Name
CHEO
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kristina Vogel
Phone
613-737-7600
Ext
3348
Email
kvogel@cheo.on.ca
First Name & Middle Initial & Last Name & Degree
Candice McGahern
Phone
613-737-7600
Ext
4111
Email
CMcGahern@cheo.on.ca
First Name & Middle Initial & Last Name & Degree
Amy Plint, MD MSc
Facility Name
CHU Sainte-Justines Hospital
City
Montréal
State/Province
Quebec
ZIP/Postal Code
HT3 1C5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stephanie Pellerin
Phone
514-345-4931
Ext
3827
Email
stephanie.pellerin.hsj@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Serge Gouin, MD
Facility Name
Children's Hospital of Winnipeg
City
Sherbrook
State/Province
Winnipeg
ZIP/Postal Code
R3A 1S1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lise Bourrier
Email
lbourrier@chrim.ca
First Name & Middle Initial & Last Name & Degree
Scott Sawyer, MD
Facility Name
Starship Children's Hospital
City
Auckland
ZIP/Postal Code
1142
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Bonisch
Email
MBonisch@adhb.govt.nz
First Name & Middle Initial & Last Name & Degree
Stuart Dalziel, MD
Facility Name
Kidz First Hospital
City
Auckland
ZIP/Postal Code
2025
Country
New Zealand
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chris Lash
Email
christopher.lash@middlemore.co.nz
First Name & Middle Initial & Last Name & Degree
Christopher Lash, MD
Facility Name
Waikato Hospital
City
Hamilton
ZIP/Postal Code
3240
Country
New Zealand
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julia Laing
Email
julia.laing@waikatodhb.health.nz
First Name & Middle Initial & Last Name & Degree
Alex Wallace, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
35410375
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.
Results Reference
derived
Learn more about this trial
Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study
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