A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants with Bronchiolitis

 
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overview

Status: Recruiting
ClinicalTrials.gov Identifier:
NCT03567473
Principal Investigator:
Dr. Amy Plint
Project Manager:
Tremaine Rowe


Population

We will enroll 1,616 infants across Canada, New Zealand, and Australia at participating sites.  We will enroll children > 60 days of age and < 12 months of age presenting with bronchiolitis during the winter viral season. Children born at less than 37-weeks’ gestation and less than 60 days corrected age and those with known chronic lung disease, congenital heart disease, immunodeficiency, recent exposure to varicella, and those who are critically unwell will not be enrolled in the study.

Objectives

Primary Objective:

  1. To determine if treatment of infants presenting with bronchiolitis to the emergency department (ED) with nebulized epinephrine and a 2-day course of oral dexamethasone is effective in reducing the need for hospitalization (due to bronchiolitis) by day 7 post enrolment compared to placebo.

Secondary Objectives:

  1. To determine if treatment of infants presenting with bronchiolitis to the ED with nebulized epinephrine and a 2-day course of oral dexamethasone is effective in reducing admissions to hospital (for bronchiolitis) at enrolment ED visit compared to placebo.

  2. To determine if there is a difference between groups in all cause admission within 21 days post enrolment, all cause health care provider visits over 21 days post enrolment, and health care-related costs.

 

Inclusion Criteria

To be eligible to participate in the study, individuals must meet all of the following 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.

  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

Individuals who meet any of the following criteria will be excluded from participation in this study:

  1. Respiratory distress assessment instrument (RDAI) score of ≤ 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 weeks

  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 37 weeks 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.

Participating Sites

This study will enroll patients at six pediatric academic EDs across Canada.

Participating Canadian sites are: 
CHU Ste. Justine (Montreal), Children’s Hospital of Eastern Ontario (Ottawa), Children’s Hospital – London Health Sciences Centre (London), Health Sciences Centre Winnipeg Children’s Hospital (Winnipeg), Alberta Children’s Hospital (Calgary), and Stollery Children’s Hospital (Edmonton). 

This study will also enroll patients at academic pediatric EDs and community EDs in New Zealand and Australia.
In New Zealand, the following hospitals will participate:
Starship Children’s Hospital, Auckland; Kidz First Hospital, Auckland; Waikato Hospital, Hamilton.
In Australia, the following hospitals will participate:
Women and Children’s Hospital, Adelaide, South Australia; Monash Medical Centre, Melbourne, VIC; Perth Children’s Hospital, Perth, WA.