Epinephrine + Dexamethasone for Bronchiolitis
(BIPED Trial)
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: < 18
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Children's Hospital of Eastern Ontario
Must not be taking: Corticosteroids, Beta-agonists
Disqualifiers: Chronic disease, Severe distress, Apnea, others
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial requires that participants have not been treated with oral, inhaled, or IV corticosteroids in the last week and have not received any beta-agonists like salbutamol or epinephrine in the ED before enrollment. If you are currently taking these medications, you may need to stop before joining the trial.
What data supports the effectiveness of the drug combination of epinephrine and dexamethasone for bronchiolitis?
Research shows that while the combination of epinephrine and dexamethasone does not significantly reduce hospital admissions or length of stay for bronchiolitis, it does improve oxygen levels in infants. Additionally, a single injection of dexamethasone alone has been shown to reduce the time needed for symptom resolution and hospital stay in young children with bronchiolitis.
12345Is the combination of epinephrine and dexamethasone safe for treating bronchiolitis in infants?
Research shows that the combination of epinephrine and dexamethasone is generally safe for infants with bronchiolitis, with no increase in serious adverse events compared to other treatments.
13678How does the drug combination of epinephrine and dexamethasone differ from other treatments for bronchiolitis?
The combination of epinephrine and dexamethasone for bronchiolitis is unique because it combines a bronchodilator (epinephrine) with a corticosteroid (dexamethasone) to potentially improve oxygen levels, although it does not significantly reduce hospital admissions or stay lengths compared to other treatments.
13469Eligibility Criteria
This trial is for infants under 12 months old who are experiencing their first episode of bronchiolitis, with symptoms like wheezing or crackles alongside an upper respiratory infection. They must not have severe respiratory distress, known chronic diseases affecting the heart/lungs, recent steroid treatment, a history of adverse reactions to steroids, prior beta-agonist treatment in the ED before enrollment, exposure to chickenpox without immunity, significant prematurity (<37 weeks and <60 days corrected age), or any barriers to follow-up.Inclusion Criteria
My child under 1 year has wheezing or crackles and signs of a cold during RSV season.
I am between 2 months and less than 1 year old.
Exclusion Criteria
My child was born prematurely and is under 60 days old, adjusted for early birth.
You have had a bad reaction to glucocorticoid medications in the past.
You have had chickenpox or been in close contact with someone who has had chickenpox, but you have not had it before.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
1-2 weeks
Treatment
Infants receive inhaled epinephrine and oral dexamethasone or placebo for 2 days
2 days
1 visit (in-person)
Follow-up
Participants are monitored for hospital admissions and health care utilization
21 days
Follow-up via telephone or email at day 7 and 21
Long-term follow-up
Monitoring of respiratory illnesses and health care utilization up to 18 years of age
Up to 18 years
Participant Groups
The study tests if inhaling epinephrine and taking oral dexamethasone reduces hospital admissions within 7 days compared to a placebo. It's a phase III trial where infants at twelve EDs will be randomly assigned double-blindly into two groups: one receiving actual treatments and the other getting placebos (fake treatments).
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Active Intervention ArmExperimental Treatment3 Interventions
Oral dexamethasone and nebulized epinephrine OR Oral dexamethasone and inhaled epinephrine given by MDI
Group II: Control ArmPlacebo Group3 Interventions
Oral 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.
Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Dexamethasone for:
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
- Immune system disorders
🇺🇸 Approved in United States as Dexamethasone for:
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
- Neoplastic diseases
- Nervous system disorders
🇨🇦 Approved in Canada as Dexamethasone for:
- Inflammation
- Allergic reactions
- Respiratory diseases
- Skin conditions
- Eye diseases
🇯🇵 Approved in Japan as Dexamethasone for:
- Inflammatory conditions
- Allergic states
- Respiratory diseases
- Blood disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Hospital of Eastern OntarioOttawa, Canada
Childrens Hospital at London Health SciencesLondon, Canada
CHEOOttawa, Canada
Stollery Children's HospitalEdmonton, Canada
More Trial Locations
Loading ...
Who Is Running the Clinical Trial?
Children's Hospital of Eastern OntarioLead Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
Children's Hospital Research Institute of ManitobaCollaborator
Research ManitobaCollaborator
Women and Children's Health Research Institute, University of AlbertaCollaborator
Alberta Children's Hospital Research InstituteCollaborator
The Hospital for Sick ChildrenCollaborator
Department of Pediatrics, Western UniversityCollaborator
St. Justine's HospitalCollaborator
References
Systematic Review and Meta-Analysis of the Efficacy and Safety of Combined Epinephrine and Corticosteroid Therapy for Acute Bronchiolitis in Infants. [2020]Objective: To evaluate the effectiveness of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. Methods: Four electronic databases (MEDLINE, EMBASE, CINAHL, and CENTRAL) were searched from their inception to February 28, 2017 for studies involving infants aged less than 24 months with bronchiolitis which assessed the use of epinephrine and corticosteroid combination therapy. The methodological quality of the included studies was assessed using the Cochrane Collaboration's Risk of Bias Tool. A random-effects meta-analysis was used to pool the effect estimates. The primary outcomes were hospital admission rate and length of hospital stay. Results: Of 1,489 citations identified, 5 randomized controlled trials involving 1,157 patients were included. All studies were of high quality and low risk of bias. Results of the meta-analysis showed no significant differences in the primary outcomes. Hospitalization rate was reduced by combinatorial therapy of epinephrine and corticosteroid in only one out of five studies, whereas pooled data indicated no benefit over epinephrine plus placebo. Clinical severity scores were significantly improved in all five RCTs when assessed individually, but no benefit was observed compared to epinephrine monotherapy when the data were pooled together. Pooled data showed that combination therapy was more effective at improving oxygen saturation level (mean difference: -0.70; 95% confidence interval: -1.17 to -0.22, p = 0.004). There was no difference in the risk of serious adverse events in infants treated with the combined epinephrine and corticosteroid therapy. Conclusions: Combination treatment of epinephrine and dexamethasone was ineffective in reducing hospital admission and length of stay among infants with bronchiolitis.
Additive effects of dexamethasone in nebulized salbutamol or L-epinephrine treated infants with acute bronchiolitis. [2016]Although it is the most common lower respiratory infection of infancy, the optimal treatment for acute bronchiolitis is still controversial. The aim of this study was to compare the early and late effects of nebulized L-epinephrine (EPI) and intramuscular dexamethasone (DEX) combination therapy with nebulized salbutamol (SAL) and dexamethasone combination and bronchodilators alone in outpatients with acute bronchiolitis.
Recent advances in the treatment of bronchiolitis and laryngitis. [2019]Progress has been made in the treatment for patients with croup and bronchiolitis in the past decade. By intervening with pharmacologic agents, a better outcome has been documented in children with these diseases. A lower probability of hospital admission means that fewer health care dollars need to be expended in this area. The present state of evidence substantiates the following. Bronchiolitis . Nebulized albuterol causes significant short-term improvement in clinical scores in bronchiolitic children, but there is no evidence that it reduces admission rates or decreases length of hospitalization. . Nebulized epinephrine results in significant improvement in clinical scores and airway resistance in children hospitalized with bronchiolitis and in the emergency department causes acute improvement in oxygenation, decreases length of time in the emergency department and admission rate to hospital. . There is no evidence to support the use of dexamethasone or other glucocorticosteroids for infants hospitalized with bronchiolitis. Croup . Nebulized budesonide or oral dexamethasone results in acute clinical improvement in outpatients with mild to moderate croup, reducing the need for hospitalization. . A combination of nebulized budesonide and oral dexamethasone may provide the best clinical outcome, although further evidence is needed to substantiate this . The required dose of oral dexamethasone may range from 0.15 mg/kg to 0.6 mg/kg for best clinical outcome. . Use of racemic epinephrine or L-epinephrine in the emergency department, especially when used concomitantly with glucocorticoids, does not require automatic hospital admission; a 3-hour observation period in the emergency department may suffice. . Use of intramuscular dexamethasone is difficult to justify in patients with croup who are able to ingest oral medications. Future studies need to examine dosing of glucocorticoids for inpatients with croup. In addition, an important question remains as to whether very mild croup patients (those with no evidence of respiratory distress) might benefit from glucocorticoids administered in the physician's office or the emergency department.
Effect of combined dexamethasone therapy with nebulized r-epinephrine or salbutamol in infants with bronchiolitis: A randomized, double-blind, controlled trial. [2021]This study investigated the effect of combining oral dexamethasone with either nebulized racemic epinephrine or salbutamol compared to bronchodilators alone for the treatment of infants with bronchiolitis.
Efficacy of dexamethasone injection for acute bronchiolitis in hospitalized children: a randomized, double-blind, placebo-controlled trial. [2013]Controversy over the efficacy of systemic corticosteroids for acute bronchiolitis initiated this study. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy of single dexamethasone injection for the treatment of acute bronchiolitis in young hospitalized children. The study, performed at the pediatric wards of a University Hospital and its affiliated hospital in Thailand, included 174 previously healthy children under 2 years of age, hospitalized with acute bronchiolitis. Each child received either a single intramuscular injection of 0.6 mg/kg dexamethasone or a placebo in addition to regular management. The primary outcome was the time from study entry to resolution of respiratory distress, determined by a clinical score derived from the respiratory rate, occurrence of wheezing, chest retraction, and oxygen saturation. Survival analysis using the Kaplan-Meier method and a log-rank test were performed. A single-dose, dexamethasone injection versus placebo produced a significant: (1) decrease in the time needed for resolution of respiratory distress (hazard ratio 1.56; 95% CI, 1.14-2.13; P = 0.005), (2) decrease in the mean duration of symptoms of 11.8 hr (95% CI, 3.9-19.7; P = 0.004), (3) decrease in the mean duration of oxygen therapy of 14.9 hr (95% CI, 5.3-24.4; P = 0.003), and (4) decrease in the mean length of hospital stay of 13.4 hr (95%CI, 2.6-24.2; P = 0.02). In conclusion, a single injection of dexamethasone yielded a significant clinical benefit for the treatment of previously healthy, young children hospitalized with acute bronchiolitis.
Efficacy of Nebulised Epinephrine versus Salbutamol in Hospitalised Children with Bronchiolitis. [2020]The use of bronchodilators in bronchiolitis lacks consensus. The efficacy of nebulised epinephrine versus salbutamol in bronchiolitis and the safety profile of the bronchodilators was studied.
Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076]. [2018]Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay.
A randomized double-blind, placebo-controlled trial of dexamethasone and racemic epinephrine in the treatment of croup. [2019]Seventy-two children hospitalized for croup received on admission a single dose of either 0.6 mg/kg dexamethasone or an equivalent placebo intramuscularly from randomized ampules; subsequently the same patients were randomized to receive either nebulized racemic epinephrine or saline by intermittent positive pressure breathing. Of the four treatment groups those receiving a placebo injection and nebulized saline had the slowest recovery by all criteria. Dexamethasone and nebulized epinephrine reduced the symptoms and hastened recovery, but dexamethasone was more effective by clinical evaluation at 6 and 12 hours post admission. The patients given dexamethasone had a significantly shorter hospital stay than those receiving placebo. We conclude that a single injection of a potent corticosteroid is beneficial in acute spasmodic croup. Nebulized racemic epinephrine given with an appropriate device is also effective, but the effect of epinephrine is less remarkable in patients treated with dexamethasone.
[Pediatrics. New treatment options for viral bronchiolitis]. [2013]The combination of nebulized epinephrine and high dose dexamethasone, or nebulized hypertonic saline, are promising new therapeutic strategies for viral bronchiolitis in the young infant. However, further research is needed before a general recommendation can be given.