Negligible Rebound in Myopia Progression Following Cessation of Treatment with 0.01% Atropine for 3 years: Year-4 Results from the CHAMP Phase 3 Clinical Trial

INTRODUCTION: Stage 2 of the Childhood Atropine for Myopia Progression (CHAMP) study was conducted to observe the safety, efficacy and rebound effects of low-dose atropine sulphate ophthalmic solutions (0.01% and 0.02%) for paediatric myopia in the year following cessation of 3 years of prior treatment. METHODS: The study was a multicentre, randomised, double-masked, placebo-controlled Phase 3 clinical trial. Children aged 3 to < 17 years with myopia (spherical equivalent refractive error (SER) from -0.50 to -6.00 D) who entered and completed Stage 1 (3 years of treatment) participated in the fourth-year follow-up (Stage 2). Stage 1 participants who were treated with atropine 0.01% or 0.02% were re-randomised 1:1:1 to atropine 0.01%, atropine 0.02% or vehicle in Stage 2. Stage 1 vehicle-treated participants were re-randomised 1:1 to atropine 0.01% or atropine 0.02% in Stage 2. Outcomes included changes in cycloplegic SER, changes in axial length (AL), responder status continuity and progression to high myopia. RESULTS: Four hundred and twenty participants were randomised in Stage 2. Negligible rebound was observed among the participants who switched from 0.01% atropine to vehicle compared to those who continued on 0.01% atropine treatment (least square mean difference in SER change from Month 36 to Month 48 between continued treatment and switching to vehicle = 0.019 D, 95% CI [-0.14, 0.18], p = 0.82 for the modified Intent to Treat set). Stage 1 responders remained responders in 83-90% of participants in various Stage 2 groups. Safety profiles were favourable, with mild, transient adverse events. CONCLUSIONS: Atropine sulphate ophthalmic solution (0.01%) exhibited negligible rebound in myopia progression after treatment cessation following 3 years of continued treatment, highlighting its potential as a treatment option. The treatment maintained a favourable safety record, and the overall benefit and risk assessment support its potential use as a long-term myopia management option. CLINICAL TRIAL REGISTRATION: The Childhood Atropine for Myopia Progression (CHAMP) study was registered in clinicaltrials.gov (NCT03350620, registration date November 17, 2017).