Abstract
OBJECTIVES: To test the feasibility and safety of exercise as an airway clearance technique (ExACT) for people with cystic fibrosis (pwCF) versus usual care (UC). METHODS: Dual-site, two-arm randomised pilot trial. Fifty pwCF (≥10 years, forced expiratory volume in 1 s (FEV(1)) ≥40% predicted), stable on Elexacaftor/Tezacaftor/Ivacaftor, were recruited, of whom 48 were randomly assigned (1:1 with minimisation) to daily ExACT (stopping all other airway clearance techniques) or UC. Feasibility was measured by recruitment, retention and adherence against preset progression criteria. Key measures of safety and signals of efficacy included spirometry (FEV(1)), lung clearance index (LCI(2.5)), pulmonary exacerbations, physical activity, treatment burden and quality of life across 28 days. Qualitative interview data and preliminary health economic data were also collected. FINDINGS: ExACT was safe over 28 days, measured by change in LCI(2.5) (ExACT -0.1 (0.6) vs UC 0.2 (0.8), mean (SD)) and FEV(1) (ExACT +2.1 (6.6) vs UC -0.8 (5.5), % predicted mean (SD)). Relative (ExACT/UC) differences of 0.97 (0.92, 1.02) for LCI(2.5) and absolute differences (ExACT-UC) of 3.2 (-0.6, 6.9) % predicted for FEV(1) suggest potential intervention efficacy. Few adverse events were reported; none serious. Recruitment and retention data suggest progression to a definitive trial, with 48/117 (41% of approached) randomised, 45/48 (92%) completing the study and a 60% overall adherence rate. DISCUSSION: Testing of our primary hypothesis within a feasibility trial showed ExACT to be a safe, acceptable and feasible intervention for pwCF. These data support advancement to a definitive, longer-term, multisite trial evaluating the safety, efficacy and cost-effectiveness of ExACT, following minor refinement. TRIAL REGISTRATION NUMBER: NCT05482048.