Bronchiolitis in Infants Placebo Versus Epinephrine and Dexamethasone Study

Bronchiolitis Clinical Trial

— BIPED  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03567473
• Other study ID #: CTO 1423
• Status: Recruiting
• Phase: Phase 3
• Start date: December 13, 2018
• Est. completion date: June 30, 2025

Study information

• Verified date: October 2023
• Source: Children's Hospital of Eastern Ontario
• Contact: Kristina I Vogel
• Phone: 613-737-7600
• Email: kvogel[@]cheo.on.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 864
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Days to 12 Months

Eligibility

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.

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.

Related Conditions & MeSH terms

• Bronchiolitis

Intervention

Drug:
• Oral dexamethasone
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
• Nebulized Epinephrine
Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
• Oral placebo
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
Two nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment
• MDI Epinephrine
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
Two doses of inhaled placebo given by MDI plus spacer, 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment.

Locations

Country	Name	City	State
Australia	Women and Children's Hospital	Adelaide
Australia	Monash Medical Centre	Melbourne
Australia	Perth Children's Hospital	Perth
Canada	Children's Hospital of Alberta	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	Childrens Hospital at London Health Sciences	London	Ontario
Canada	CHU Sainte-Justines Hospital	Montréal	Quebec
Canada	CHEO	Ottawa	Ontario
Canada	Children's Hospital of Winnipeg	Sherbrook	Winnipeg
New Zealand	Kidz First Hospital	Auckland
New Zealand	Starship Children's Hospital	Auckland
New Zealand	Waikato Hospital	Hamilton

Sponsors (9)

Lead Sponsor	Collaborator
Children's Hospital of Eastern Ontario	Alberta Children's Hospital Research Institute, Canadian Institutes of Health Research (CIHR), Children's Hospital Research Institute of Manitoba, Department of Pediatrics, Western University, Research Manitoba, St. Justine's Hospital, The Hospital for Sick Children, Women and Children's Health Research Institute, University of Alberta

Countries where clinical trial is conducted

Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Safety outcome 2: Serious Bacterial Infection	meningitis, osteomyelitis or septicaemia	up to 21 days post enrollment
Other	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
Other	Safety outcome 4: Death	Death	up to 21 days post enrollment
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	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
Other	Exploratory Outcome 8: Out of pocket expenses	transportation, days of missed work, missed leisure activities	up to 21 days post enrollment
Other	Exploratory Outcome 9: Age dependent variation in the efficacy of epinephrine and dexamethasone	to determine if treatment efficacy varies by age	up to 21 days post enrollment
Other	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
Other	Exploratory Outcome 11: Development of respiratory illnesses	asthma, wheezing and other respiratory illnesses	Up to 18 years of age
Primary	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
Secondary	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
Secondary	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.	up to 21 days post enrollment
Secondary	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
Secondary	Health Care related costs within the 21 days following enrollment ED visits.	Health care related costs	up to 21 days post enrollment