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

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

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)

Study Overview

• Status: Terminated
• Conditions: Asthma in Children
• Intervention / Treatment: Drug: Budesonide Formoterol Drug Combination; Drug: nebulisation of terbutaline

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Amelle Issa; Phone Number: +33157022632; Email: amelle.issa@chicreteil.fr

Study Locations

• France
  • Boulogne-Billancourt, France
    • CHU Ambroise Pare
  • Clamart, France
    • CHU Antoine Béclère
  • Corbeil-Essonnes, France
    • Centre Hospitalier Sud Francilien
  • Créteil, France, 94000
    • CHI Créteil
  • Jossigny, France
    • Grand Hôpital de l'Est Francilien
  • Le Kremlin-Bicêtre, France, 94270
    • CHU Bicêtre
  • Lille, France
    • CHU Lille
  • Villeneuve-Saint-Georges, France
    • CHI Villeneuve-Saint-Georges

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: budesonide/formoterol Turbuhaler®; 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; 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).
Active Comparator: nebulisation of terbutaline; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Intercommunal Creteil
• Collaborators: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2021
• Primary Completion (Actual): September 23, 2021
• Study Completion (Actual): June 23, 2023

Study Registration Dates

• First Submitted: January 4, 2021
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (Actual): January 12, 2021

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Budesonide; Formoterol Fumarate; Terbutaline; Budesonide, Formoterol Fumarate Drug Combination
• Other Study ID Numbers: ASTHMAFAST

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No