A Randomised Controlled Trial of the efficacy and safety of an Inhaled Corticosteroid and Long Acting Beta Agonist as maintenance and reliever therapy versus as prescribed maintenance with salbutamol as reliever therapy in children with moderate and severe asthma.

INTERVENTION: Combination Inhaled Corticosteroid + Long‐Acting Beta2‐Agonist (ICS‐LABA). Budesonide‐formoterol (100micrograms/6micrograms) metered dose inhaler (MDI) (Vannair®) as single maintenance and reliever therapy (SMART) via spacer (Airflow Space Chamber Plus 220 ml). 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, for 52 weeks. GINA step 2: 1 inhalation once daily + 1 inhalation as needed GINA step 3: 1 inhalation once OR twice daily + 1 inhalation as needed GINA step 4: 2 inhalations twice daily + 1 inhalation as needed GINA steps will be assessed by the investigator at study entry and 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. Participants will be asked to contact investigators for urgent review (unscheduled visit) within seven days of a severe asthma exacerbation. During this review, participants will potentially have their standard treatment stepped up in accordance with the SMARTCARE stepwise treatment algorithm approach, if not already done so by their usual doctor or the medical team treating their acute asthma. 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 m CONDITION: Asthma; ; Asthma Respiratory ‐ Asthma PRIMARY OUTCOME: Asthma exacerbations (moderate and severe) as rate per participant per year.; This will be assessed as a composite outcome.[A moderate asthma exacerbation is defined as worsening asthma leading to either:; •An urgent, unplanned medical review e.g. primary care or emergency department (ED) visit or hospital admission <24 hours; not resulting in the prescription of systemic corticosteroids (tablets, suspension, or injection) e.g. oral prednisone; OR; •The use of systemic corticosteroids for < 3 days, which does not meet the criteria for a severe asthma exacerbation e.g. use of systemic corticosteroids from a non‐acute prescription, such as a home supply or delayed prescription.; ; A severe asthma exacerbation is defined as worsening asthma leading to either: ; •An urgent, unplanned medical review e.g. primary care or ED visit, or hospital admission and resulting in the prescription of systemic corticosteroids (tablets, suspension, or injection) e.g. oral prednisone; OR; •The use of systemic corticosteroids for >=3 days; •A hospital admission for >=24 hours.; ; For a severe asthma exacerbation to be counted as a separate event, it must be preceded by at least seven days during which no criteria for a severe asthma exacerbation are fulfilled. ; For a moderate asthma exacerbation to be counted as a separate event, it must be preceded by at least seven days during which no criteria for a moderate or severe asthma exacerbation are fulfilled.; ; Asthma exacerbations will be reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits. 52 weeks from the date intervention commenced.] SECONDARY OUTCOME: Adverse Events.[Examples of known AEs include oral thrush, hoarseness, rapid or irregular heartbeat, tremor, and headache. These will be determined by participant/parent/guardian self‐report and/or medical records, utilising Common Terminology Criteria for Adverse Events (CTCAE). 52 weeks from the date intervention commenced.] Asthma control.[Asthma Control Questionnaire (ACQ‐5) at 26 and 52 weeks. This is a validated questionnaire for measuring asthma control. 26 and 52 weeks from the date intervention commenced.] Composite of asthma exacerbations (moderate and severe), or step‐up in treatment, as rate per participant per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Days in hospital due to asthma per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Days lost from preschool/school due to asthma per year (participant).[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. 52 weeks from the date intervention commenced.] Days lost from work due to childcare for asthma per year (parent(s)/guardian(s)).[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. 52 weeks from the date intervention commenced.] Fractional exhaled Nitric Oxide (FeNO) at 52 weeks.[Measured using a NIO XVERO® device. 52 weeks from the date intervention commenced.] Growth velocity.[Height measured using a stadiometer. 52 weeks from the date intervention commenced.] Hospital admissions due to asthma as a rate per participant per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Incremental cost per moderate and/or severe exacerbation averted. ; This will be assessed as a composite outcome.[Cost‐effectiveness acceptability curves will be generated to estimate the uncertainty around this value. The base‐case analysis takes a health system perspective (asthma‐related resource utilisation) in the 12‐month follow‐up period. Secondary analyses will include monetised time off school (participant) and time off from work (parent(s)/guardian(s)). Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period.] Moderate asthma exacerbations as rate per participant per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] On‐treatment Forced Expiratory Volume over 1 second (FEV1) z score at 52 weeks.[Measured using an NND Easy‐on PC Spirometer. 52 weeks from the date intervention commenced.] Proportion of participants on each treatment step.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Proportion of participants who discontinue treatment or withdraw.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. 52 weeks from the date intervention commenced.] Proportion of participants with at least one asthma exacerbation (moderate and severe), or step‐up in treatment. ; This will be assessed as a composite outcome.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Proportion of participants with at least one asthma exacerbation (moderate and severe). ; This will be assessed as a composite outcome.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Proportion of participants with at least one severe asthma exacerbation.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Proportion of participants with at least one step‐up in treatment.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Serious Adverse Events.[Examples of SAEs include severe allergic reaction and severe spasm in the airways. These will be determined by participant/parent/guardian self‐report and/or medical records, utilising Common Terminology Criteria for Adverse Events (CTCAE). 52 weeks from the date intervention commenced.] Severe asthma exacerbations as rate per participant per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Step‐up in treatment, as rate per participant per year.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Time to first asthma exacerbation (moderate or severe), or step‐up in treatment. ; This will be assessed as a composite outcome.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. Measured from the date intervention commenced, to the date the first asthma exacerbation begins, or treatment is stepped up.] Time to first moderate or severe asthma exacerbation. ; This will be assessed as a composite outcome.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. Measured from the date intervention commenced, to the date the first asthma exacerbation begins.] Time to first severe asthma exacerbation.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. Measured from the date intervention commenced, to the date the first severe asthma exacerbation begins.] Time to first step‐up in treatment.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team and/or reported and reviewed at study visits by investigator. Participant NHI number and medical records will be used to validate data for the full 52 week study period. Measured from the date intervention commenced, to the date the treatment is stepped up.] Total composite inhaled beta2‐agonist dose.[Determined through counting of remaining doses in returned inhalers. 52 weeks from the date intervention commenced.] Total inhaled corticosteroid and systemic corticosteroid dose. ; This will be assessed as a composite outcome.[Determined through counting of remaining doses in returned inhalers. Additionally, reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] Total inhaled corticosteroid dose.[Determined through counting of remaining doses in returned inhalers. 52 weeks from the date intervention commenced.] Total systemic corticosteroid dose.[Reported by the participant and their parent(s)/guardian(s) using study logbooks, and reviewed at study visits by the study team. Participant NHI number and medical records will be used to validate data for the full 52 week study period. 52 weeks from the date intervention commenced.] INCLUSION CRITERIA: 1. Aged 4 to 11 years 2. Doctor or Nurse Practitioner (NP) diagnosis of asthma (self‐report by parent/participant or healthcare provider‐reported) 3. Use of maintenance ICS or ICS‐LABA + SABA reliever therapy in the last 6 months (i.e. GINA step 2, 3 and 4) 4. Registered with a General Practitioner (GP) 5. Willing and able to switch from current treatment regimen