EPIDEX: Nebulized Adrenalin and Oral Betamethasone in Children With Bronchiolitis Attending Pediatric Emergencies.

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Terminated

CT.gov ID

NCT02586961

Collaborator

Institut National de la Santé Et de la Recherche Médicale, France (Other)

195

Enrollment

Location

Arms

Duration (Months)

8.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The combined administration of high dose of oral betamethasone and nebulization of adrenaline seems to be an attractive therapeutic alternative for reducing the rate of hospitalization for acute bronchiolitis treated in the emergency department. However, it is essential to confirm the trend previously observed with this treatment before using it in current practice.

Condition or Disease	Intervention/Treatment	Phase
Children Bronchiolitis	Drug: 0.9% saline solution Drug: oral betamethasone placebo Drug: adrenaline Drug: oral betamethasone	Phase 2/Phase 3

Detailed Description

Rationale: In infancy, bronchiolitis is the most common acute infection of the lower respiratory tract and is most often caused by the respiratory syncytial virus (RSV). The current treatment of bronchiolitis is controversial. Although meta-analysis of nebulized bronchodilators or corticosteroids treatments failed to show any consistent benefits on admission rate, they remain widely used in pediatric emergency wards. A recent randomized, double-blind, placebo-controlled, clinical trial with a factorial design was conducted to determine whether treatment with nebulized epinephrine, a short course of high dose of oral Betamethasone, or both, resulted in a clinically important decrease in hospital admissions among infants with bronchiolitis who were seen in the emergency department. This study showed that infants in the epinephrine-betamethasone group were significantly less likely than those in the placebo group to be admitted by day 7 (relative risk, 0.65; 95% confidence interval, 0.45 to 0.95, P = 0.02). However, after adjustment for multiple comparisons, this result became insignificant (P = 0.07). This synergistic interaction was not anticipated but gave hope that the association nebulized epinephrine - short course of oral high dose of betamethasone might reduce the risk of hospitalization for infants who consulted pediatric emergencies for a moderate to severe acute bronchiolitis. It is therefore required to conduct a trial dedicated to this evaluation in the French population.

Hypothesis: using Epinephrine-Betamethasone allows to reduce the rate of hospitalization of mild-to-severe acute viral bronchiolitis seen in pediatric emergency departments.

Study Design

Study Type:

Interventional

Actual Enrollment :

195 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Nebulized Adrenalin and Oral Betamethasone in Children With Bronchiolitis Attending Pediatric Emergencies : a Multicentre Randomized Controlled Trial

Study Start Date :

Oct 1, 2015

Actual Primary Completion Date :

Sep 1, 2017

Anticipated Study Completion Date :

Oct 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 0.9% saline solution - oral betamethasone placebo Control arm: 0.9% saline solution - oral betamethasone placebo	Drug: 0.9% saline solution Placebo: Nebulized 0.9% saline solution Drug: oral betamethasone placebo placebo of oral betamethasone: equivalent of 1 mg/kg at inclusion followed by five once-daily doses
Experimental: adrenaline - oral betamethasone Experimental arm : adrenaline and betamethasone	Drug: adrenaline Catecholamine nebulized adrenaline (3 ml of 1:1000 solution) Drug: oral betamethasone Mineralocorticoid: a short course of oral betamethasone: 1.0 mg/kg at inclusion, followed by five once-daily doses (0.6 mg/kg)

Arm

Intervention/Treatment

Placebo Comparator: 0.9% saline solution - oral betamethasone placebo

Control arm: 0.9% saline solution - oral betamethasone placebo

Drug: 0.9% saline solution

Placebo: Nebulized 0.9% saline solution

Drug: oral betamethasone placebo

placebo of oral betamethasone: equivalent of 1 mg/kg at inclusion followed by five once-daily doses

Experimental: adrenaline - oral betamethasone

Experimental arm : adrenaline and betamethasone

Drug: adrenaline

Catecholamine nebulized adrenaline (3 ml of 1:1000 solution)

Drug: oral betamethasone

Mineralocorticoid: a short course of oral betamethasone: 1.0 mg/kg at inclusion, followed by five once-daily doses (0.6 mg/kg)

Outcome Measures

Primary Outcome Measures

Hospital admission up to 7 days after enrollment, which occurred during the visit in the emergency department [7 days after enrollment]
determine whether treatment with nebulized adrenaline (3 ml of 1:1000 solution) and a short course of oral dexamethasone (1.0 mg/kg) followed by five once-daily doses (0.6 mg/kg) results in a 10% decrease in hospital admissions among infants with mild-to-severe bronchiolitis seen in emergency departments

Secondary Outcome Measures

PICU admission rate following examination in the emergency ward [during the 7 days after enrollment]
Estimate and compare the percentages of infants in each group requiring Pediatric Intensive Care Unit (PICU admission).
Length of hospitalization for infants admitted for bronchiolitis in the following 7 days after inclusion [7 days after enrollment]
Assess whether experimental treatment reduces healing time and duration of hospitalization of infants included in the study and who have been admitted
Variation of RDAI scores before and after nebulization [between enrollment and an average of 7 days (the end hospitalization)]
Compare clinical scores of respiratory distress before/after treatment
Adverse events during the following 7 days after inclusion [7 days after enrollment]
Evaluate the tolerance of experimental treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Weeks to 12 Months

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Infants aged 6 weeks to 12 months admitted in paediatric emergency
First episode of acute bronchiolitis defined as: expiratory dyspnea with breath slowing and/or sibilants and/or crackles preceded by (or associated with) a nasopharyngitis more or less febrile
Respiratory distress assessment index score (RDAI) of 4 to 15 after a nasopharyngeal clearance
Agreement of at least one of the parents for his child to participate in biomedical research
Affiliation to social security (beneficiary or entitled), except beneficiary of State medical help

Exclusion Criteria:

Prematurity (less than 37 weeks of gestation)
Antecedent of invasive respiratory ventilation during neonatal period
Antecedent of lung or chronic cardiac pathology of wich rhythm disorder, acute obstructive cardiomyopathy and coronary insufficiency
Immune deficiency
Active viral infection (hepatitis, zona, herpes, varicella, HIV)
Proven or suspected tuberculosis
Exposure to varicella during 15 days before inclusion
Severe distress (defined as one of following signs: a pulse rate >200/min, respiratory rate >80/min, RDAI score >15, neurological disorders)
Nebulization (aerosol spray) of Salbutamol or other bronchodilator treatment during the 24 hours before the inclusion
Inhalation (spray) of Salbutamol during the preceding 24 hours
Oral or inhaled corticosteroids during the preceding 2 weeks
Previous episode of wheezing or ascertained diagnosis of asthma
Hypersensitivity to one of the constituting of oral betamethasone
Vaccination by living vaccine during the preceding 2 weeks