APPENDIX A: SCHEDULE OF TRIAL PROCEDURES...............................................................45

9.15 Unscheduled visits

Participants and Investigators may arrange additional visits. Reasons for these visits include:

9.15.1 Unscheduled visit following a severe asthma attack

Acute management of a severe asthma attack is determined by the medical team treating the participant. Following discharge, participants should follow any prescribed weaning regimen (this will likely include a SABA for both treatment arms). Participants will be asked to record the dose and duration of this treatment.

Participants should contact Investigators for urgent review within seven days of an acute severe asthma attack. During this review, participants will have their standard treatment stepped up in accordance with the CARE stepwise treatment algorithms (Appendix E), if not already done so by their usual doctor or the medical team treating their acute asthma.

Investigators will only escalate treatment following a severe attack. A participant’s usual doctor may choose to step up a participant’s treatment for another reason, such as poor asthma symptom control. Change of treatment to non-study medication will not result in the participant being withdrawn from the study. If safe, Investigators will change the participant’s inhaler medication to align with the CARE stepwise treatment algorithm (e.g. changing a beclomethasone inhaler to a fluticasone inhaler). Treatment will not be de-escalated. The GP will be informed of any change of treatment.

9.15.2 Unscheduled visit for dispensing of trial medication

If a participant or their parent(s)/caregiver(s) require additional inhalers (e.g. due to high-use, loss of inhaler(s), or inhaler(s) not working properly), they should contact their Investigator to arrange a visit as soon as practically possible.

At the visit, participants will be reviewed for AEs and SAEs and their inhaler technique assessed (with re-training as necessary). If a participant or their parent(s)/caregiver(s) report high-use, then the following action will be taken (as detailed in the asthma action plans, Appendix D):

High-use Action

More than 6 puffs of their reliever inhaler a day, for one week

See their GP within one week to review, add, or amend their current maintenance therapy More than 12 puffs a day Go to the hospital or see their doctor today More than 16 puffs a day They need to attend ED immediately

9.15.3 Unscheduled visit for consideration of withdrawal

Participants and their parent(s)/guardian(s) have the right to withdraw from the study at any time. They do not have to provide a reason.

Investigators may withdraw a participant from the study at any time. Reasons for withdrawal include:

 Pregnancy

 Ineligibility (either arising during the trial or retrospectively having been overlooked at screening)

 An adverse event which results in inability to comply with trial procedures