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Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study

Phase 3
Recruiting
Conditions
Bronchiolitis
Interventions
Drug: Oral dexamethasone
Drug: Oral placebo
Drug: Nebulized Epinephrine
Drug: Nebulized normal saline
Drug: MDI Epinephrine
Drug: MDI placebo
Registration Number
NCT03567473
Lead Sponsor
Children's Hospital of Eastern Ontario
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
864
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.

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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active Intervention ArmOral dexamethasoneOral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
Active Intervention ArmNebulized EpinephrineOral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
Active Intervention ArmMDI EpinephrineOral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
Control ArmOral 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.
Control ArmNebulized normal salineOral 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.
Control ArmMDI 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.
Primary Outcome Measures
NameTimeMethod
Admission to hospital for bronchiolitis within 7 days post enrollment7 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
NameTimeMethod
Admission to hospital for bronchiolitis at the time of the enrollment ED visitEnrollment 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 visitup to 21 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.

Health Care related costs within the 21 days following enrollment ED visits.up to 21 days post enrollment

Health care related costs

All cause Health care provider visits (including ED visits) by day 21 following enrollment EDup to 21 days post enrollment

Visits to ED, other clinic, primary care provider, or any visit to see a nurse or physician following enrollment

Trial Locations

Locations (12)

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

Children's Hospital of Eastern Ontario

🇨🇦

Ottawa, Ontario, Canada

Childrens Hospital at London Health Sciences

🇨🇦

London, Ontario, Canada

Stollery Children's Hospital

🇨🇦

Edmonton, Alberta, Canada

Starship Children's Hospital

🇳🇿

Auckland, New Zealand

CHU Sainte-Justines Hospital

🇨🇦

Montréal, Quebec, Canada

Children's Hospital of Winnipeg

🇨🇦

Sherbrook, Winnipeg, Canada

Kidz First Hospital

🇳🇿

Auckland, New Zealand

Waikato Hospital

🇳🇿

Hamilton, New Zealand

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