Determinants Of Oral Corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY)

The aim of the prospective cohort study is to: (1) document the magnitude of response to oral corticosteroids administered to children presenting to the emergency department with moderate or severe asthma and (2) quantify clinically available potential determinants of the response to corticosteroids, such as age, gender, triggers of the index exacerbation, environmental tobacco smoke (ETS), gene polymorphisms, and their interactions.

Study Overview

• Status: Completed
• Conditions: Asthma

Detailed Description

The objective of the large multicentre cohort study is to quantify the response to oral corticosteroids in children aged 1 to 17 years presenting to the ED with a moderate or severe asthma exacerbation.

The main outcome is hospital admission within 72 hours of the oral corticosteroid administration.

Secondary outcomes include the change in Pediatric Respiratory Assessment Measure (PRAM), length of active treatment and other markers of response to therapy in the ED as well as markers of recovery over the next 10 days.

• Study Type: Observational
• Enrollment (Actual): 1011

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G2
    • Centre Hospitaliser de l'Université Laval
  • Ontario
    • London, Ontario, Canada, N6A 2V5
      • Children's Hospital of London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L1
      • Children's Hospital of Eastern Ontario
  • Quebec
    • Montreal, Quebec, Canada, H3T1C5
      • CHU Sainte-Justine (CHUSJ)
    • Montreal, Quebec, Canada, H3H 1P3
      • Montreal Children's Hospital (MCH)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Children aged 1 to 17 years with moderate to severe asthma with Pediatric Respiratory Assessment Measure (PRAM) ≥4.

Description

Inclusion Criteria:

• Subject will be eligible if he/she:

  1. is aged 1 to 17 years,
  2. has not received any oral, IM or IV corticosteroid within the last 5 days?
  3. Presents to the hospital emergency department with an acute episode of cough, wheezing and/or dyspnea?

  4. Has asthma as defined as one or more of the following 6 criteria:

     (i) prior diagnosis of asthma made by a physician; OR (ii) prior documented episode of acute cough, wheezing and/or dyspnea with significant response to inhaled β2-agonists or to oral corticosteroids; OR (iii) in a child aged <2 years, 3 or more episodes of cough, wheezing and/or dyspnea, including the index visit; OR (iv) previous lung function tests showing significant reversibility post-bronchodilation (≥12% FEV1 or ≥25% Rrs at 4 to 8 Hz); OR (v) a positive provocation test (PC20 ≤8 mg/mL or Provocation Dose (to increase Rrs by 50% or more (PD50) ≤8 mg/mL), OR (vi) the current episode diagnosed or suspected of asthma by the emergency physician?

  5. have moderate or severe airway obstruction, defined as a Paediatric Respiratory Asthma Measure (PRAM) score >3 at baseline,

Exclusion Criteria:

• Patient will be excluded if :

  1. he/she has another chronic respiratory condition (such as bronchopulmonary dysplasia or cystic fibrosis);
  2. there is a reasonable suspicion of bronchiolitis or foreign body aspiration;
  3. he/she has a prior history of hypersensitivity to salbutamol, ipratropium bromide or oral prednisone/prednisolone;
  4. he/she has a relative or absolute contraindication to receiving oral corticosteroids such as recent exposure to varicella or live vaccine in past 14 days,
  5. there is confirmed or suspected pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Oral corticosteroids (OCS); All patients receive: Prednisone or Prednisolone at 1 mg/kg (in 1 site) or 2 mg/kg (in all other sites) (max. 50 mg); if vomiting prednisone/prednisolone: they receive dexamethasone (0.3 mg/kg, max. 10 mg); 2 to 3 doses of salbutamol within the first hour of therapy according to severity Those with severe exacerbations receive 3 treatments with salbutamol and ipratropium bromide within the initial hour of therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital admission	Hospital admission or Length of active treatment for 8 or more hours after the oral corticosteroid administration or ED return visit associated with hospital admission within 72 hours after the oral corticosteroid administration or ED return visit associated within 72 hours with length of active treatment for 8 or more hours after the oral corticosteroid administration	72 hours after oral corticosteroids administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of active treatment in hospital		8 hours after oral corticosteroid administration
Meeting the severity criteria for admission	Proportion of children with a PRAM score ≥4 within 4 hours of oral corticosteroid administration	Within 4 hours of oral corticosteroid administration
PRAM profile in the ED	Area under the curve of the PRAM measured hourly for the time of oral corticosteroid (OCS) until 4 hours after OCS	Within 4 hours of oral corticosteroid administration
Time to meeting discharge criteria	Time until PRAM score ≤ 3	Within 8 hours of oral corticosteroid administration
Change in respiratory resistance	Change in respiratory resistance between baseline and disposition will be documented on the MasterScreen Impulse Oscillometry (Cardinal Health Canada, Montreal, Canada) using previously described standardized techniques in cooperative children aged ≥3 years. (measured in a subset of individuals)	Within 4 hours of oral corticosteroid administration
Unscheduled visits for asthma	unscheduled visits for asthma as reported by parents and confirmed by medical charts.	Within 7 days of the index ED exacerbation
Symptom score	Area under the curve of symptoms measured daily on the validated Asthma flare-up diary for children	Within 7 days of the index ED exacerbation
Duration of asthma symptoms	Duration of symptoms measured daily on the validated Asthma flare-up diary for children	Within 7 days of the index ED exacerbation
Cumulative reliever use	Cumulative number of puffs of reliever medication as recorded daily on the Asthma flare-up diary for children	Within 7 days of the index ED exacerbation
Duration of use of rescue ß2-agonists	Duration of use of rescue ß2-agonists as recorded on the Asthma flare-up diary for children	Within 7 days of the index ED exacerbation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Number of children with vomiting, serious Infection, psychosis, and mood disturbances	Within 7 days of the index ED exacerbation
Serious Adverse Health Events	Number of children with adverse events requiring hospitalization, prolonged hospitalization, life threatening, other medically important events or associated with significant disability or incapacity	Within 7 days of the index ED exacerbation

Collaborators and Investigators

• Sponsor: St. Justine's Hospital
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Principal Investigator: Francine M Ducharme, MD., M.Sc., CHU Sainte Justine, University of Montreal

Publications and helpful links

General Publications

• Tse SM, Krajinovic M, Chauhan BF, Zemek R, Gravel J, Chalut D, Poonai N, Quach C, Laberge S, Ducharme FM; DOORWAY research group of the Pediatric Emergency Research in Canada (PERC) network. Genetic determinants of acute asthma therapy response in children with moderate-to-severe asthma exacerbations. Pediatr Pulmonol. 2019 Apr;54(4):378-385. doi: 10.1002/ppul.24247. Epub 2019 Jan 15.
• Merckx J, Ducharme FM, Martineau C, Zemek R, Gravel J, Chalut D, Poonai N, Quach C; Pediatric Emergency Research Canada (PERC) DOORWAY team. Respiratory Viruses and Treatment Failure in Children With Asthma Exacerbation. Pediatrics. 2018 Jul;142(1):e20174105. doi: 10.1542/peds.2017-4105. Epub 2018 Jun 4.
• Ducharme FM, Zemek R, Chauhan BF, Gravel J, Chalut D, Poonai N, Guertin MC, Quach C, Blondeau L, Laberge S; DOORWAY research group of the Pediatric Emergency Research in Canada (PERC) network. Factors associated with failure of emergency department management in children with acute moderate or severe asthma: a prospective, multicentre, cohort study. Lancet Respir Med. 2016 Dec;4(12):990-998. doi: 10.1016/S2213-2600(16)30160-6. Epub 2016 Jul 20.
• Ducharme FM, Zemek R, Gravel J, Chalut D, Poonai N, Laberge S, Quach C, Krajinovic M, Guimont C, Lemiere C, Guertin MC. Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations. BMJ Open. 2014 Apr 7;4(4):e004699. doi: 10.1136/bmjopen-2013-004699.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: December 11, 2013
• First Submitted That Met QC Criteria: December 11, 2013
• First Posted (Estimate): December 17, 2013

Study Record Updates

• Last Update Posted (Estimate): July 22, 2014
• Last Update Submitted That Met QC Criteria: July 18, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: Asthma; Children; Cohort study; Corticosteroids
• Additional Relevant MeSH Terms: Signs and Symptoms, Respiratory; Respiratory Sounds
• Other Study ID Numbers: CHUSJ