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Nebulized Epinephrine and Oral Dexamethasone in Bronchiolitis

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ClinicalTrials.gov Identifier: NCT03567473
Recruitment Status : Not yet recruiting
First Posted : June 25, 2018
Last Update Posted : June 25, 2018
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Children's Hospital Research Institute of Manitoba
Research Manitoba
Women and Children's Health Research Institute, Univesrity of Alberta
Alberta Children's Hospital Research Institute
The Hospital for Sick Children
Department of Pediatrics, Western University
St. Justine's Hospital
Information provided by (Responsible Party):
Amy Plint, Children's Hospital of Eastern Ontario

Brief Summary:
We hypothesize that infants with bronchiolitis treated with nebulized 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 six study EDs will be enrolled to one of two study groups: (1) nebulized epinephrine and oral dexamethasone or (2) nebulized normal saline 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.

Condition or disease Intervention/treatment Phase
Bronchiolitis Drug: Oral dexamethasone Drug: Nebulized Epinephrine Drug: Oral placebo Drug: Nebulized normal saline Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1616 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial Comparing Epinephrine and Dexamethasone to Placebo in the Treatment of Infants With Bronchiolitis
Estimated Study Start Date : December 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2023


Arm Intervention/treatment
Experimental: Active Intervention Arm
Oral dexamethasone and nebulized epinephrine
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

Drug: Nebulized Epinephrine
Two nebulized treatments of 3 mL 1:1000 epinephrine 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment

Placebo Comparator: Control Arm
Oral placebo (OraBlendTM in Canada and a compounded oral placebo solution at New Zealand/Australia sites) and nebulized saline.
Drug: 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.

Drug: Nebulized normal saline
Two nebulized treatments of 3 mL of normal saline 30 minutes apart (+/- 15 minutes) at the time of emergency department enrolment




Primary Outcome Measures :
  1. Admission to hospital for bronchiolitis within 7 days post enrollment [ Time Frame: 7 days post enrollment ]
    A physician writing "admit to ward" orders or similar language, 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 :
  1. Admission to hospital for bronchiolitis at the time of the enrollment ED visit [ Time Frame: Enrollment visit ]
    A physician writing "admit to ward" orders or similar language, 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.

  2. All cause admission to Hospital within 21 days following enrollment ED visit [ Time Frame: up to 21 days post enrollment ]
    A physician writing "admit to ward" orders or similar language, 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.

  3. All cause Health care provider visits (including ED visits) by day 21 following enrollment ED [ Time Frame: up to 21 days post enrollment ]
  4. Health Care related costs within the 21 days following enrollment ED visits. [ Time Frame: up to 21 days post enrollment ]
    Health care related costs


Other Outcome Measures:
  1. Safety outcome 1: Gastrointestinal bleeding [ Time Frame: up to 21 days post enrollment ]
    involving melena or frank blood per rectum (and not attributable to other causes, as determined by the treating physician

  2. Safety outcome 2: Serious Bacterial Infection [ Time Frame: up to 21 days post enrollment ]
    Urinary tract infection, meningitis, osteomyelitis or septicaemia

  3. Safety outcome 3: Severe Varicella [ Time Frame: up to 21 days post enrollment ]
    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

  4. Safety outcome 4: Death [ Time Frame: up to 21 days post enrollment ]
    Death

  5. Exploratory Outcome 1: Admission to hospital for bronchiolitis within 21 days following enrollment ED visit [ Time Frame: up to 21 days post enrollment ]
    A physician writing "admit to ward" orders or similar language, 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.

  6. Exploratory Outcome 2: Admission to ICU within 21 days following enrollment ED visit for bronchiolitis and requiring intubation or continuous positive airway pressure (CPAP) [ Time Frame: up to 21 days post enrollment ]
    Physician admitting patient to ICU for bronchiolitis and requiring oxygen or ventilatory support

  7. Exploratory Outcome 3: All cause admission to hospital with 7 days following enrollment ED visit [ Time Frame: up to 7 days post enrollment ED visit ]
    A physician writing "admit to ward" orders or similar language, 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.

  8. Exploratory Outcome 4: All cause ED visits within 21 days following enrollment ED visit [ Time Frame: up to 21 days post enrollment ED ]
    Visits to the ED after initial enrollment ED visit

  9. Exploratory Outcome 5: Length of stay for the enrollment ED visit (in hours) [ Time Frame: Enrollment ED visit ]
    defined as discharge time minus oral study medication time, for participants discharged at the enrollment ED

  10. Exploratory Outcome 6: Length of hospital admission for those patients admitted at their enrollment visit [ Time Frame: Admissions at enrollment ED visit ]
    time of hospital discharge minus the time of oral study medication

  11. Exploratory Outcome 7: Symptoms [ Time Frame: up to 21 days post enrollment ]
    cough, noisy breathing, respiratory distress, sleep and ability to feed

  12. Exploratory Outcome 8: Out of pocket expenses [ Time Frame: up to 21 days post enrollment ]
    transportation, days of missed work, missed leisure activities



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Days to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 respiratory syncytial virus (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.
  3. Respiratory distress assessment instrument (RDAI) score of > 3. This RDAI will ensure children very mild respiratory diseases are not enrolled. This is the lower limit of the RDAI range used in CanBEST.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. Presenting with symptoms of apnea prior to enrollment.
  4. Treatment with oral, inhaled, or IV corticosteroids within the last 2 weeks or a history of adverse reaction to glucocorticoids.
  5. 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.
  6. Insurmountable language barrier (patient's parent/guardian is unable to understand English or French to give informed consent and participate in follow-up).
  7. 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.
  8. Previous enrolment in the trial.
  9. Unavailability for follow-up period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03567473


Contacts
Contact: Tremaine T Rowe 613-737-7600 ext 3348 trowe@cheo.on.ca
Contact: Candice McGahern 613-737-7600 ext 4111 CMcGahern@cheo.on.ca

Locations
Australia
Royal Children's Hospital Not yet recruiting
Melbourne, Australia, 3052
Contact: Sharon O'Brien       Sharon.O'Brien@health.wa.gov.au   
Principal Investigator: Ed Oakley, MD         
Monash Medical Centre Not yet recruiting
Melbourne, Australia, 3168
Contact: Simon Craig, MD         
Princess Margaret Hospital Not yet recruiting
Perth, Australia, 6008
Contact: Meredith Borland       Meredith.Borland@health.wa.gov.au   
Canada, Alberta
Children's Hospital of Alberta Not yet recruiting
Calgary, Alberta, Canada, T3B 6A9
Contact: Jennifer Crotts    403-955-7445    Jennifer.Crotts@ahs.ca   
Principal Investigator: Graham Thompson, MD         
Stollery Children's Hospital Not yet recruiting
Edmonton, Alberta, Canada, T6G 2C8
Contact: Manasi Rajogopal    (780)-248-5440    manasi@ualberta.ca   
Principal Investigator: Andrew Dixon, MD         
Canada, Ontario
Childrens Hospital at London Health Sciences Not yet recruiting
London, Ontario, Canada, N6A 5W9
Contact: Kamary Coriolano       Kamary.CoriolanoDaSilva@lhsc.on.ca   
Principal Investigator: Gary Joubert, MD         
CHEO Not yet recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Tremaine Rowe    613-737-7600 ext 3348    trowe@cheo.on.ca   
Contact: Candice McGahern    613-737-7600 ext 4111    CMcGahern@cheo.on.ca   
Principal Investigator: Amy Plint, MD MSc         
Canada, Quebec
CHU Sainte-Justines Hospital Not yet recruiting
Montréal, Quebec, Canada, HT3 1C5
Contact: Marie-Christine Auclair    514-345-4931 ext 3827    marie.christine.auclair@recherche-ste-justine.qc.ca   
Principal Investigator: Serge Gouin, MD         
Canada, Winnipeg
Children's Hospital of Winnipeg Not yet recruiting
Sherbrook, Winnipeg, Canada, R3A 1S1
Contact: Lise Bourrier       lbourrier@chrim.ca   
Principal Investigator: Scott Sawyer, MD         
New Zealand
Starship Children's Hospital
Auckland, New Zealand, 1142
Kidz First Hospital Not yet recruiting
Auckland, New Zealand, 2025
Contact: Jocelyn Neutze         
Waikato Hospital Not yet recruiting
Hamilton, New Zealand, 3240
Contact: Alex Wallace         
Sponsors and Collaborators
Children's Hospital of Eastern Ontario
Canadian Institutes of Health Research (CIHR)
Children's Hospital Research Institute of Manitoba
Research Manitoba
Women and Children's Health Research Institute, Univesrity of Alberta
Alberta Children's Hospital Research Institute
The Hospital for Sick Children
Department of Pediatrics, Western University
St. Justine's Hospital
Investigators
Principal Investigator: Amy Plint, MSc, MD Childrens Hospital of Eastern Ontario (CHEO)

Responsible Party: Amy Plint, MD, MSc, FRCPC, Research Chair in Pediatric Emergency Medicine, Children's Hospital of Eastern Ontario
ClinicalTrials.gov Identifier: NCT03567473     History of Changes
Other Study ID Numbers: CTO 1423
First Posted: June 25, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Bronchiolitis
Bronchitis
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Tract Infections
Dexamethasone acetate
Dexamethasone
Epinephrine
Racepinephrine
Epinephryl borate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents