ABSTRACTBackground and ObjectivesTreatable trait‐based personalised medicine improves outcomes in severe asthma clinics. We assessed the feasibility of a randomised controlled trial (RCT) of protocolised treatable trait‐guided asthma management in patients not under a severe asthma clinic.MethodsTen week single‐group cohort study. Participants had a doctor's diagnosis of asthma, Asthma Control Questionnaire‐5 (ACQ‐5) score > 1, and ≥ 1 exacerbation in the last year. Intervention: biomarker‐guided asthma medication according to a protocolised algorithm, targeting traits of type‐2 inflammation and airflow obstruction. Feasibility outcomes: recruitment rates, acceptability of intervention, willingness to enrol in an RCT, need for ‘extended’ trait assessment after 10 weeks, and estimation of trait prevalence.ResultsRecruitment ceased with 29/50 participants after 14 months due to difficulties associated with COVID‐19. Recruitment rate: 29/118 (25%) of those invited to participate (95% CI 17 to 33). 24/26 (92%) participants found the intervention acceptable and were willing to participate in a future study. After 10 weeks, 65% remained not well controlled (ACQ‐5 > 1) and would have required the ‘extended’ assessment. Participants had a mean (SD) 4.8 (2.3) of 13 traits assessed.ACQ‐5 improved during the study by −1.0 (0.3 to 1.8) units, and post‐bronchodilator airflow limitation reduced from 59% of participants to 35%. 12/29 (41%) participants received continuous oral corticosteroids at some point during the study.ConclusionProtocolised treatable trait management was acceptable to participants, associated with significant clinical benefit, and a full RCT appears feasible. Targeting type‐2 inflammation and airflow obstruction was insufficient to control asthma in the majority of patients, despite marked systemic corticosteroid exposure.Trial Registration: ACTRN12620000935932