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

NCT04705727 | Terminated Phase 3 DMC

• 1 other identifier: ASTHMAFAST
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 8

Brief Summary

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)

Conditions

Asthma in Children

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• Number of hospitalized patients

  during the month following the asthma attack

• Time spent in ER

  Up to discharge from the emergency room

• Score for the inhalation technique

  Immediately after each inhalation procedure

• Score on the Asthma Control Questionnaire (ACT)

  1 week after randomisation

• Score on the Asthma Control Questionnaire (ACT)

  1 month after randomisation

Study Arms (2)

budesonide/formoterol Turbuhaler®

EXPERIMENTAL

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

nebulisation of terbutaline

ACTIVE COMPARATOR

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

Interventions

Budesonide Formoterol Drug Combination DRUG

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).

budesonide/formoterol Turbuhaler®

nebulisation of terbutaline DRUG

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.

nebulisation of terbutaline

Eligibility Criteria

• Age: 8 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Intercommunal Creteil: lead
• AstraZeneca: collaborator

Study Sites (8)

CHU Ambroise Paré

Boulogne-Billancourt, France

Location

CHU Antoine Béclère

Clamart, France

Location

Centre Hospitalier Sud Francilien

Corbeil-Essonnes, France

Location

CHI Créteil

Créteil, 94000, France

Location

Grand Hôpital de l'Est Francilien

Jossigny, France

Location

CHU Bicêtre

Le Kremlin-Bicêtre, 94270, France

Location

CHU Lille

Lille, France

Location

CHI Villeneuve-Saint-Georges

Villeneuve-Saint-Georges, France

Location

MeSH Terms

Interventions

Budesonide, Formoterol Fumarate Drug Combination

Intervention Hierarchy (Ancestors)

Formoterol Fumarate; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Budesonide; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 12, 2021
• Study Start: August 23, 2021
• Primary Completion: September 23, 2021
• Study Completion: June 23, 2023
• Last Updated: July 27, 2023

Record last verified: 2023-07

Locations

FR (8)