None listed
Conditions
Brief summary
The global burden of childhood asthma is significant, and New Zealand has one of the highest prevalence rates in the world. The greatest individual burden of paediatric asthma is in those children with moderate and severe disease (GINA steps 2+). The traditional approach to managing asthma is to prescribe a maintenance Inhaled Corticosteroid or Inhaled Corticosteroid-Long-Acting Beta2-Agonist (ICS or ICS-LABA) inhaler and/or a Short-Acting Beta2-Agonist (SABA) reliever, taken as needed for symptom relief. However, there are a number of safety concerns with this approach: • The benefits of ICS are restricted in clinical practice by the overestimation of asthma control and, in some cases, steroid aversion. This leads to the under prescribing of ICS by clinicians, and reduced adherence to ICS by patients. • The number of ICS inhalations patients can use each day are effectively capped, with no effective mechanism to titrate the ICS dose according to need, particularly during acute asthma exacerbations. • SABAs can provide quick symptom relief but they lack activity against the underlying inflammatory processes in asthma. Overreliance during an acute attack can therefore lead to a delay in seeking medical assistance. • Both ICS underuse and SABA overuse are associated with asthma mortality. Combining an ICS with a LABA, such as formoterol, in a single inhaler offers a potential solution to protect against the dangers of beta2-agonist monotherapy and poor ICS adherence, by ensuring that an ICS dose is delivered with each “reliever” inhalation. Equally as important, the ICS dose is titrated according to need, with increased steroid being delivered during an acute worsening episode requiring increased beta2-agonist use. ICS-formoterol, used as both Maintenance And/or Reliever Therapy (MART), is now the GINA-preferred treatment option for adolescents and adults with asthma across all treatment steps. Further research is urgently needed to evaluate the efficacy and safety of ICS-formoterol as maintenance and/or reliever therapy, and to bring the strength of evidence and available treatment options for children on par with adults and adolescents. If comparable efficacy with ICS-formoterol maintenance and/or reliever therapy is shown in childhood asthma, then implementation of this regimen would markedly reduce the burden of asthma in all children. We therefore propose an RCT to compare the safety and efficacy of two treatment regimens in mild, moderate and severe childhood asthma: 1. A combination ICS/LABA as both maintenance and/or reliever therapy 2. ICS or ICS/LABA maintenence therapy with a separate SABA reliever therapy
Interventions
Combination Inhaled Corticosteroid + Long-Acting Beta2-Agonist (ICS-LABA).
Budesonide-formoterol 100micrograms/6micrograms Dry Powder Inhaler (DPI Turbuhaler). Regimen and dose will be adjusted according to the Global INitiative for Asthma (GINA) step at study entry, with maintenance and/or reliever use as needed for relief of asthma symptoms and prior to exercise, for 52 weeks.
GINA step 2: 1 inhalation as needed
GINA step 3: 1 inhalation once daily, and 1 inhalation as needed
GINA step 4: 1 i
Combination Inhaled Corticosteroid + Long-Acting Beta2-Agonist (ICS-LABA). Budesonide-formoterol 100micrograms/6micrograms Dry Powder Inhaler (DPI Turbuhaler). Regimen and dose will be adjusted according to the Global INitiative for Asthma (GINA) step at study entry, with maintenance and/or reliever use as needed for relief of asthma symptoms and prior to exercise, for 52 weeks. GINA step 2: 1 inhalation as needed GINA step 3: 1 inhalation once daily, and 1 inhalation as needed GINA step 4: 1 inhalation twice daily, and 1 inhalation as needed GINA steps will be assessed by the investigator at study entry and the run-in period aligned to existing treatment (per the steroid equivalence table in the protocol). During the course of the study, participant’s GINA step will be re-assessed and adjusted by the investigator based on the escalation criteria: following an acute severe asthma exacerbation, or following two moderate asthma exacerbations. If the escalation criteria is met, their standard treatment will be stepped up, in accordance with the START CARE stepwise treatment approach, if not already done so by their usual doctor or their treating medical team. The intervention will be participant- and/or parent-administered. There is no maximum daily frequency of administration of the intervention, however participants will receive a written asthma action plan detailing when to seek medical help (participant's using more than 6 reliever inhalations in one day will be advised to go to the hospital or see their doctor today). Adherence will not be monitored.
Sponsors
Medical Research Institute of New Zealand
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
5 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
1. Patients of any gender age five to 11 years (inclusive) 2. Doctor diagnosis of asthma (self-report by parent/participant or healthcare provider-reported) 3. Use of ICS or ICS-LABA maintenance plus SABA reliever therapy (corresponding to GINA step 2, 3 or 4) in the 6 months prior to Visit 1 4. Registered with a General Practitioner 5. Satisfactory Turbuhaler technique 6. Inspiratory flow measurement of between 30 and 90 L/min 7. Provision of written informed consent (parent/guardian) and assent (participant) 8. Able and willing to switch from current treatment regimen For randomisation at Visit 2, participants should fulfil the following criterion: 9. Satisfactory Turbuhaler technique 10. Inspiratory flow measurement of between 30 and 90 L/min
Exclusion criteria
1. Already using ICS-formoterol or ICS-Salbutamol as a reliever 2. Any use of high dose ICS-LABA (New Zealand Child Asthma Guidelines Step 5), biologics, maintenance oral corticosteroids (i.e. GINA Step 5), or leukotriene receptor antagonists in the last 6 months 3. Any use of systemic corticosteroids in the 6 weeks prior to Visit 1 4. Use of a beta-blocker in the 6 months prior to Visit 1 5. Any medical condition which, at the Investigator’s discretion, may present a safety risk or impact the feasibility of the study or the study results (including, but not limited to, other significant respiratory comorbidities, such as cystic fibrosis and bronchiectasis) 6. Any known or suspected hypersensitivity (including rash, urticaria, angioedema, bronchospasm and anaphylactic reaction) to the active substances prescribed in the study (budesonide, formoterol, terbutaline), lactose or milk protein (excipient) 7. Any intravenous therapy for the treatment of asthma, in the last year. 8. Previous Intensive Care Unit admission for asthma, or ventilation for asthma, ever 9. Participation in another clinical trial of an investigational medicinal product in the 30 days prior to Visit 1 For randomisation at Visit 2, participants are excluded from the study if the following criteria apply: 10. Any severe exacerbation, or 2 moderate exacerbations (per protocol defined criteria) and/or a change in asthma treatment other than run-in study medication from Visit 1 until Visit 2
Outcome results
None listed