Description of a randomised controlled trial of inhaled corticosteroid/fast-onset LABA reliever therapy in mild asthma

Abstract

This paper describes the rationale and design of the Novel START (Symbicort Turbuhaler Asthma Reliever Therapy) randomised controlled trial of inhaled corticosteroid (ICS)/fast-onset long-acting β-agonist (LABA) reliever therapy in mild asthma.The main focus of clinical research and management in asthma is on patients with moderate or severe asthma. There is little attention paid to the "silent majority" with asthma who experience so-called intermittent and mild persistent asthma. These patients are often taking inhaled short-acting β-agonist (SABA) therapy alone, to provide symptom relief. However, while use of SABA therapy alone does provide symptom relief, there is little robust evidence supporting the long-term efficacy and safety of treating mild asthma with a SABA alone, or to guide clinicians and patients when to initiate regular low-dose ICS therapy. Further, doctors and patients find it difficult to recognise the need for ICS therapy when symptoms are infrequent and in this situation poor adherence to ICS is common. This has led to consideration of alternative regimens to regular ICS prescription for intermittent or mild asthma.A combination inhaler containing both an ICS and fast-onset LABA, which is used solely as reliever therapy, may be superior to SABA reliever therapy alone, and might be an alternative to regular ICS with SABA reliever therapy in patients with intermittent or mild asthma [1][2][3][4]. Combination ICS/fast-onset LABA reliever therapy allows titration of ICS therapy according to symptoms. This may increase ICS use in patients who over-rely on their SABA and are otherwise poorly adherent to maintenance ICS therapy, and may actually represent what patients, prescribed regular combination ICS/fast-onset LABA treatment, take in the "real world" [5,6].

Description of the protocol for the PRACTICAL study: a randomised controlled trial of the efficacy and safety of ICS/LABA reliever therapy in asthma

“…Based on this evidence, two double-blind regulatory RCTs of as-needed budesonide/formoterol (SYmbicort Given as needed in Mild Asthma, SYGMA) are currently underway, 21 together with an open-label RCT of as-needed budesonide/formoterol in patients currently taking only SABA reliever therapy (Novel Symbicort Therapy As Reliever Therapy, Novel START). 22 To investigate the efficacy and safety of budesonide/formoterol ICS/fast-onset LABA as sole reliever therapy in a broader population of patients for whom ICS is currently indicated, the PRACTICAL (PeRsonalised Asthma Combination Therapy with an Inhaled Corticosteroid And fast-onset Long acting beta agonist) trial will therefore be undertaken (ACTRN12616000377437). The PRACTICAL study is an open-label study funded by the government-funded Health Research Council of New Zealand and has undergone full external peer review as part of the funding process.…”

The paradoxes of asthma management: time for a new approach?

“…In mild asthma, these as-needed strategies, employing co-administered ICS/SABA or ICS/LABA ("partnered ICS approach"), better match treatment to patient behaviour than the current once-or twice-daily maintenance regimens. It will be vital to conduct studies to show this as a superior approach to SABA as needed, and not inferior to regular ICS for mild asthma [26,27], as well as ensure effective communication, especially to those with mild asthma, regarding the safety of intermittent use of ICS.…”

Emerging Concepts in Evidence-Based Asthma Management

“…Studies have already been performed with an ICS/SABA combination 52 (not widely available) and with separate ICS and SABA inhalers. 53,54 Two regulatory and two pragmatic studies of as-needed budesonide/formoterol combination are currently underway in mild asthma, 55,56 primarily focusing on protection from exacerbations. Issues that will need to be considered for this regimen include whether a minimum number of prn inhalations need to be taken each week for protection from exacerbations, and if so, how "asthma control" should be assessed, or whether a rapid increase in as-needed ICS/LABA when asthma worsens is sufficient to protect from severe exacerbations.…”