Atropine Eyedrops for Myopia Progression in Children and Adolescents (MODERATO STUDY)
brief summary
Myopia, or shortsightedness, is a multifactorial disorder, governed by environmental and genetic factors. Myopia is the most common ocular disorder worldwide with an increasing prevalence over the past few decades and affecting the quality of life and economic health of individuals worsening socio-economic problems. Progressive myopia is nearly exclusively a condition of childhood and adolescence, as in most young adults, myopia has stabilized. Myopia frequently appears in childhood, with a peak incidence occurring between 8 and 10 years of age. The most used topical pharmacological intervention for managing childhood myopia progression is atropine, a non-selective muscarinic antagonist, which has been widely used in clinical trials in concentrations ranging from 0.01% to 1.0%. Atropine is at present the agent with the highest efficacy and optimal safety profile to reduce myopia progression in children and adolescents. MODERATO study, a phase III, prospective, multicentric, randomized, double blind, multiple doses, placebo-controlled parallel-group, adaptive study, aims to evaluate the efficacy and safety of 0.025% and 0.05% atropine eye drops in children and adolescents aged 3 to under 18 years old over a 24-month period, to understand its ability to manage and stop myopia getting worse. It will be conducted in 11 centers in Italy, Spain, Poland, the UK and Albania.
detailed description
The MODERATO study is a phase III, prospective, multicentric, randomized, double-blind, parallel group, adaptive, placebo-controlled trial. The study will be conducted in primary care and hospital settings in 3 European countries (Italy, Spain, Poland), in the UK and in Albania, involving a total of 11 centers.
The study hypothesis is that low dose (0.025% and 0.05%) of atropine eye drops will reduce the myopia progression in children and adolescents (3-18 years of age) compared with placebo eye drops, over 24 months.
A total of 234 participants from 5 countries will be estimated to take part in the study.
Eligible participants with myopia with a spherical equivalent refraction of both eyes at least -0.75 D at baseline will be randomized to treatment (0.025% atropine eye drops, 0.05% atropine eye drops) and placebo groups in 1:1:1 ratio. Each arm will consist of at least 78 individuals.
In this study, the primary objective is to evaluate efficacy of 0.025% and 0.05% atropine eye drops in children and adolescents over 24 months to slow the progression of myopia.
A formal interim efficacy analysis on the primary endpoint will be planned when the 50% of the total planned sample size has completed the 1-year treatment follow-up (105 evaluable patients in total: 35 in each arm).
"EARLY ESCAPE" Phase of Patients after Six Months of Atropine Eye Drops Treatment At the sixth month of treatment, if the patients who received the placebo treatment show worsening of their myopia, they will be switched to the active treatment. This approach is called "early escape", which ensures that the patients receive the best treatment as soon as possible, reducing the time during which they may receive ineffective treatment. The analysis will be conducted by a team of experts, Data Safety Monitoring Committee (DSMC). The treatment after the early escape will be carried out as open label study. Blinding will be maintained for the patients who do not early escape.
Analysis after One Year of Treatment When half of the patients in our study complete one year of treatment, a comprehensive analysis will be conducted to assess the effectiveness of the main treatment. This means that the results will be considered when data from 105 patients have been collected (35 in each group).
The Bayesian inference statistical technique will be used to combine and adapt the data collected during the treatment monitoring period.
official title
A Phase III, Randomized, Double-blind, Multiple Doses, Placebo-controlled, Parallel-group Adaptive Study to Evaluate the Efficacy and Safety of Atropine for the Treatment of Myopia Progression in Children and Adolescents (MODERATO Study)