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

Assistance Publique - Hôpitaux de Paris

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Bronchiolitis; Children

Treatments: Drug: oral betamethasone; Drug: oral betamethasone placebo; Drug: 0.9% saline solution; Drug: adrenaline

Study type: Interventional

Funder types: Other

Identifiers

NCT02586961

2015-002477-38 (EudraCT Number)

P140929

Details and patient eligibility

About

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.

Full 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.

Enrollment: 195 patients

Sex: All

Ages: 6 weeks to 12 months old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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195 participants in 2 patient groups, including a placebo group

0.9% saline solution - oral betamethasone placebo

Placebo Comparator group

Description:

Control arm: 0.9% saline solution - oral betamethasone placebo

Treatment:

Drug: oral betamethasone placebo

Drug: 0.9% saline solution

adrenaline - oral betamethasone

Experimental group

Description:

Experimental arm : adrenaline and betamethasone

Treatment:

Drug: oral betamethasone

Drug: adrenaline