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| Name | Class |
|---|---|
| Canadian Institutes of Health Research (CIHR) | OTHER_GOV |
| Children's Hospital Research Institute of Manitoba | OTHER |
| Research Manitoba | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Intervention Arm | Experimental | Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Enrollment visit |
| All cause admission to Hospital within 21 days following enrollment ED visit |
| Measure | Description | Time Frame |
|---|---|---|
| Safety outcome 1: Gastrointestinal bleeding | involving melena or frank blood per rectum (and not attributable to other causes, as determined by the treating physician) | up to 21 days post enrollment |
| Safety outcome 2: Serious Bacterial Infection |
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.
*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.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Amy Plint, MSc, MD | Childrens Hospital of Eastern Ontario (CHEO) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Women and Children's Hospital | Adelaide | 5006 | Australia | |||
| Monash Medical Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41225556 | Derived | 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. | |
| 35410375 |
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| Women and Children's Health Research Institute, Canada |
| OTHER |
| Alberta Children's Hospital Research Institute | OTHER |
| The Hospital for Sick Children | OTHER |
| Department of Pediatrics, Western University | UNKNOWN |
| St. Justine's Hospital | OTHER |
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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.
|
| Nebulized Epinephrine | Drug | Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment |
|
|
| 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. |
|
|
| 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 |
|
|
| 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. |
|
|
| 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. |
|
|
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. |
| 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 | up to 21 days post enrollment |
| Health Care related costs within the 21 days following enrollment ED visits. | Health care related costs | up to 21 days post enrollment |
meningitis, osteomyelitis or septicaemia
| up to 21 days post enrollment |
| Safety outcome 3: Severe Varicella | 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 | up to 21 days post enrollment |
| Safety outcome 4: Death | Death | up to 21 days post enrollment |
| Exploratory Outcome 1: Admission to hospital for bronchiolitis within 21 days following enrollment ED visit | 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. | up to 21 days post enrollment |
| Exploratory Outcome 2: Admission to ICU within 21 days following enrollment ED visit for bronchiolitis and requiring intubation or continuous positive airway pressure (CPAP) | Physician admitting patient to ICU for bronchiolitis and requiring oxygen or ventilatory support | up to 21 days post enrollment |
| Exploratory Outcome 3: All cause admission to hospital with 7 days following enrollment ED visit | 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. | up to 7 days post enrollment ED visit |
| Exploratory Outcome 4: All cause ED visits within 21 days following enrollment ED visit | Visits to the ED after initial enrollment ED visit | up to 21 days post enrollment ED |
| Exploratory Outcome 5: Length of stay for the enrollment ED visit (in hours) | defined as discharge time minus oral study medication time, for participants discharged at the enrollment ED | Enrollment ED visit |
| Exploratory Outcome 6: Length of hospital admission for those patients admitted at their enrollment visit | time of hospital discharge minus the time of oral study medication | Admissions at enrollment ED visit |
| Exploratory Outcome 7: Resolution of symptoms as documented on a standardized questionnaire during the telephone or email at day 7 and 21 days. | cough, noisy breathing, respiratory distress, sleep and ability to feed | up to 21 days post enrollment |
| Exploratory Outcome 8: Out of pocket expenses | transportation, days of missed work, missed leisure activities | up to 21 days post enrollment |
| Exploratory Outcome 10: Health care utilization (including ambulatory visits, ED visits, hospitalization) for respiratory illness | future health care utilization | Up to 18 years of age |
| Exploratory Outcome 11: Development of respiratory illnesses | asthma, wheezing and other respiratory illnesses | Up to 18 years of age |
| Melbourne |
| 3168 |
| Australia |
| Perth Children's Hospital | Perth | 6008 | Australia |
| Children's Hospital of Alberta | Calgary | Alberta | T3B 6A9 | Canada |
| Stollery Children's Hospital | Edmonton | Alberta | T6G 2C8 | Canada |
| Childrens Hospital at London Health Sciences | London | Ontario | N6A 5W9 | Canada |
| Children's Hospital of Eastern Ontario | Ottawa | Ontario | K1H 8L1 | Canada |
| CHU Sainte-Justines Hospital | Montreal | Quebec | HT3 1C5 | Canada |
| Children's Hospital of Winnipeg | Sherbrook | Winnipeg | R3A 1S1 | Canada |
| Starship Children's Hospital | Auckland | 1142 | New Zealand |
| Kidz First Hospital | Auckland | 2025 | New Zealand |
| Waikato Hospital | Hamilton | 3240 | New Zealand |
| 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. |
| ID | Term |
|---|---|
| D001988 | Bronchiolitis |
| ID | Term |
|---|---|
| D001991 | Bronchitis |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D003907 | Dexamethasone |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |
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