# Anti-inflammatory reliever therapy for asthma using inhaled budesonide/formoterol as-needed with or without maintenance in South African children (AIR-SA 001): a description of a randomised clinical trial protocol

## TL;DR

This study tests a new asthma treatment in South African children using a combined inhaler to see if it reduces severe asthma attacks better than current methods.

## Contribution

The trial evaluates budesonide/formoterol as a combined anti-inflammatory reliever in children under 12, a novel approach in low- to middle-income countries.

## Key findings

- The trial will assess if budesonide/formoterol reduces severe asthma exacerbations in children aged 6–18.
- It will compare this treatment to the current standard of separate inhaled corticosteroids and short-acting beta agonists.
- The study will also evaluate quality of life, lung function, and health economics outcomes.

## Abstract

Asthma is the most common non-communicable disease among children, with increasing prevalence. The current standard of care in high-income countries in adults and adolescents includes the use of combination inhaled corticosteroids (ICSs) with rapid-onset long-acting ß2 agonists (LABA) for all severities of asthma. The primary objective of this trial is to assess the efficacy of a budesonide/formoterol inhaler used ‘both as required, and regularly’ to reduce asthma exacerbations compared with the standard of care for asthma in children and adolescents.

Children and adolescents aged 6–18 years with a diagnosis of asthma with at least one asthma exacerbation in the previous 12 months will be randomised to receive either budesonide/formoterol inhaler or the standard of care, which includes ICS and short-acting ß2 agonist (SABA). The primary outcome will be the number of severe asthma exacerbations over 1-year follow-up period. Secondary objectives will include evaluating the quality of life, lung function and health economic outcomes.

The current standard of care in South Africa recommends use of separate ICSs and SABA inhalers for asthma management in children with no recommendation for ICS/LABA in children under the age of 12 years for non-severe asthma. Budesonide/formoterol has transformed asthma treatment in high-income countries for use ‘as needed’ as anti-inflammatory reliever and for maintenance and reliever in adolescence, 12−18 years and adults. This strategy has been shown to reduce asthma exacerbations and hospitalisations. This trial will bridge the gap for the efficacy of budesonide/formoterol in children <12 years of age and address the economic arguments and safety of this approach for implementation in the lower to middle income countries. If this trial demonstrates positive results in the study population, it could provide strong scientific evidence and policy relevance to be adopted by policymakers for clinical implementation.

This study has been registered and approved by the South African Health Regulatory Authority 20231016, on 14 December 2023, KwaZulu Natal Health Research Committee KZ_202304_008 on 11 January 2024, University of KwaZulu Natal Biomedical Research Ethics Committee BREC/0000/5663/2023 on 6 February 2024, South African Clinical Trials Register DOH-27-032024-4778 on 14 March 2024, ClinicalTrial.gov NCT06429475 on 20 May 2024 and Pan African Clinical Trial Registry on 27 February 2025; the unique identification number for the registry is PACTR202502547023775.