Budesonide/Formoterol Turbuhaler® Versus Terbutaline Nebulization as Reliever Therapy in Children With Moderate Asthma Exacerbation

Study Overview
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Brief Summary
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Combined use of inhaled corticosteroids and long-acting β-agonists (LABAs) as the controller and the quick relief therapy termed single maintenance and reliever therapy (SMART) is a potential therapeutic regimen for the management of persistent asthma. A recent systematic review supports the combined use of inhaled corticosteroids and LABA as both the controller and quick relief therapy (SMART) among patients aged 12 years. In Emergency room (ER), Meta-analysis showed that using salbutamol (or albuterol) by meter doses inhaler (MDI) with a valved holding chamber (VHC) in children with moderate-severe acute asthma exacerbation was more effective, that is, fewer hospital admissions, more clinical improvement, and had fewer adverse effects (tremor and tachycardia) than salbutamol by nebulizer. Therefore, several international guidelines recommend the use of salbutamol by MDI rather than by nebulizer for moderate-severe asthma exacerbations. In children older than 8 years old, dry-powder inhaler (DPI), a device that delivers medication to the lungs in the form of a dry powder is currently used for maintenance and reliever therapy rather than MDI. In this context, we aim to assess the use of combined inhaled corticosteroids and long-acting β-agonists (LABAs) as a quick relief therapy in children older than 8 years old presenting at the ER with moderate asthma exacerbation. Acute asthma patients who had severe exacerbation were excluded from this study (these patients receiving systematically continuous nebulized salbutamol and/or intravenous salbutamol upon their arrival)

Official Title
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Comparison of the Efficacy and Safety of Budesonide/Formoterol Turbuhaler® Versus Terbutaline Nebulization as Reliever Therapy in Children With Asthma Presenting at the Emergency Room for Moderate Exacerbation

Conditions
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Asthma in Children

Intervention / Treatment
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* Drug: Budesonide Formoterol Drug Combination
* Drug: nebulisation of terbutaline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 8-17 years Children consulting to the ER with moderate asthma exacerbation (defined by the Pulmonary Score > 3 and ≤7) Score for the inhalation technique = 3 French social security affiliation Exclusion Criteria: Pneumonia Pulmonary and/or cardiac congenital malformations Chronic pulmonary disease other than asthma (bronchopulmonary dysplasia, cystic fibrosis, or post infectious bronchiolitis obliterans) Foreign body aspiration Neurological alteration Severe asthma exacerbation defined by Pulmonary Score > 7 Cardiopulmonary failure imminent or mechanical ventilation indication Thyrotoxicosis, pheochromocytoma, type 2 diabetes, untreated hypokalemia, obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other serious cardiovascular disorders such as ischemic heart disease, tachyarrhythmias or severe heart failure. Pregnancy Breastfeeding woman Ongoing participation in RIPH1 Intervention Research History of intolerance to terbutaline Hypersensitivity to the active ingredient or any excipients of terbutaline Hypersensitivity (allergy) to budesonide, formoterol or any component of the product (lactose may contain milk proteins in small quantities) Patient with an ongoing treatment of itraconazole, ritonavir or other potent CYP3A4 inhibitor, quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors (MAOIs), beta-blockers (including eyedrops) and tricyclic antidepressants

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: budesonide/formoterol Turbuhaler®<br>After randomization, patients in the experimental arm will receive budesonide/formoterol Turbuhaler® 100/6 μg, one inhalation every 5 minutes (Maximum 12 inhalations). | Drug: Budesonide Formoterol Drug Combination<br>* This combination will be used to treat the asthma exacerbation, patients will take one inhalation of budesonide/formoterol Turbuhaler® 100/6 μg every 5 minutes (Maximum 12 inhalations).<br>|
| Active Comparator: nebulisation of terbutaline<br>0.1 mg/kg nebulized terbutaline 5 mg/2 ml of Terbutaline dilution diluted with 2 ml normal saline delivered by an air compressor nebuliser driven by oxygen at a flow rate of 8l/min. The duration of one dose will be approximately 20 minutes and a total of 3 doses will be administered. In case of an insufficient response, 3 additional doses will be administered for a maximum of 6 nebulisations. | Drug: nebulisation of terbutaline<br>* Patients will receive 0.1 mg/kg nebulized terbutaline 5 mg/2 ml of Terbutaline dilution diluted with 2 ml normal saline delivered by an air compressor nebuliser driven by oxygen at a flow rate of 8l/min. The duration of one dose will be approximately 20 minutes and a total of 3 doses will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of success | Percentage of success define by a pulmonary score < 3 according to the number of administrations necessary to obtain this score. | Up 30 minutes after the last administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of hospitalized patients | Number of hospitalized patients | during the month following the asthma attack | 
| Time spent in ER | Number of hours of stay in the ER | Up to discharge from the emergency room | 
| Score for the inhalation technique | Score for the inhalation technique at each procedure from 0 to 3 | Immediately after each inhalation procedure | 
| Score on the Asthma Control Questionnaire (ACT) | Score on the Asthma Control Questionnaire (ACT) | 1 week after randomisation | 
| Score on the Asthma Control Questionnaire (ACT) | Score on the Asthma Control Questionnaire (ACT) | 1 month after randomisation | 
| Number of medical visit | Number of medical visits at 1 week and 1 month following the exacerbation | 1 week and 1 month following the exacerbation | 
| controlled asthma | Number of patients with a controlled asthma at 1 month following the exacerbation | 1 month following the exacerbation | 
| Adverse events | Number of adverse events | Up to 1 month following the exacerbation | 
| FEV1 | FEV1 volume at 1 month | 1 month | 
| Total pulmonary capacity | Total pulmonary capacity at 1 month | 1 month | 
| Vital capacity (VC) | Vital capacity volume at 1 month | 1 month | 
| FEV1/FVC ratio | FEV1/FVC ratio at 1 month | 1 month | 
| Pulmonary score | Pulmonary score at each procedure from 0 to 9 | Within 5 minutes following each inhalation procedure | 
| Oxygen saturation | Oxygen saturation at each procedure expressed as a percentage | Within 5 minutes following each inhalation procedure | 
| Respiratory rate | Respiratory rate number of breathing cycles per minute | Within 5 minutes following each inhalation procedure |