Low-dose Atropine for Myopia Control in Children

Phase 2

Active, not recruiting

• Conditions: Myopia, Progressive
• Interventions: Drug: Atropine eye drops, 0.02%; Drug: Atropine eye drops, 0.01%; Drug: Placebo (NaCl 0.9%) eye drops

• Registration Number: NCT03865160
• Lead Sponsor: University Eye Hospital, Freiburg

Brief Summary

Myopia (nearsightedness) is the most common eye disorder. Only second to age, it is the main risk factor for major degenerative eye diseases such as glaucoma, macular degeneration or retinal detachment. Their risk increases with the degree of myopia. Hence, prevention of myopia and slowing its progression is of high relevance. Almost all clinical studies, including two large randomised clinical trials (RCT) were performed in Asia with Asian study participants. The results indicate that atropine eye drops can attenuate myopic progression in children, even in low concentrations thus minimizing unwanted side effects. However, the cumulative evidence is yet not strong enough to recommend their unrestricted use, especially in a Non-Asian population. We therefore intend to set up an adequately powered RCT comparing atropine 0.02% eye drops with placebo to validate previous findings and to test whether this therapeutic concept holds its promise in a European population.

Detailed Description

Myopia (nearsightedness) is the most common developmental eye disorder in the first decades of life. It is the biggest risk factor for sight threatening degenerative eye diseases later in life, second only to age. Its prevalence is increasing worldwide in pandemic dimensions affecting now \> 80% in Asian and \> 40% in Caucasian populations. Myopia is one of the five eye diseases identified as immediate priorities by the WHO's global initiative for the elimination of avoidable blindness. It usually develops during primary school and its onset and progression are related to environmental factors such as near work and lack of day light exposure, to a lesser degree to genetic factors. Therefore, retardation of myopia progression is a major therapeutic goal. Clinical trials from Asia have shown that 0.01% atropine eye drops can attenuate progression of myopia while inducing only little side effects such as light sensitivity and reduced accommodation. Subsequent data also from Asia have suggested that a concentration of 0.05% atropine is slightly more effective with a still acceptable level of adverse effects. However, it is unclear whether this therapy is equally and sufficiently efficacious in a Caucasian population. It is also unclear which concentration of atropine represents the best compromise between efficacy and safety. Our own uncontrolled pilot data suggest that 0.01% delays progression by about 50% with negligible side effects, but that 0.05% induces a pupil dilation of \> 3 mm, which is considered unacceptable. Due to the increasing prevalence also in Europe and an increasing demand from parents for means to retard myopia progression, the trial is the first European large scale randomized clinical trial investigating the safety and efficacy of 0.01% and 0.02% atropine eye drops in comparison to placebo drops. Such a trial is mandatory to substantiate the increasing off-label prescriptions of low-dose atropine in children and to develop clinical guidelines.

Study Timeline

• Study First Submitted: 2019-03-03
• Study First Submitted QC: 2019-03-05
• Study First Posted: 2019-03-06
• Study Start: 2021-10-19
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-06
• Primary Completion: 2025-11
• Study Completion: 2027-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 302

Inclusion Criteria

1. Male or female patients aged 8 to 12 years (up to the day before the 13th birthday)
2. Myopia of -1 D to -6 D with reported or documented annual progression ≥ 0.5 D of myopia
3. Written informed consent obtained from patient (if applicable) and parents or legal guardians according to international guidelines and local laws
4. Ability to understand the nature of the trial and the trial related procedures and to comply with them

Exclusion Criteria

1. Asian or African origin
2. Abnormal binocularity
3. Strabismus
4. Astigmatism >1.5 D
5. Anisometropia >1.5 D
6. History of amblyopia
7. Corrected visual acuity in any eye <0.63
8. Any acquired or developmental organic eye disease
9. Premature birth
10. Any known systemic metabolic disease or chromosomal anomaly
11. Previous use of any kind of contact lenses
12. Previous use of atropine eye drops
13. Epilepsy
14. Known hypersensitivity to the active substances or any of the excipients
15. Participation in any other interventional clinical trial within the last 30 days before the start of this trial
16. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registries and diagnostic trials is allowed
17. Contraindications according to the Summary of Product Characteristics (SmPC): Increased intraocular pressure (primary forms of glaucoma or narrow angle glaucoma), chronic rhinitis sicca
18. Caution and pediatric counselling shall be assured if any of the following conditions are present according to the Summary of Product Characteristics (SmPC): Cardiac insufficiency, arrhythmia, coronary stenosis, hyperthyroidism, stomach or bowel stenosis, bowel paralysis, megacolon, muscle weakness, lung edema, hypersensitivity to atropine, spastic paralysis
19. Parents or children with poor understanding of the German language
20. Person who is in a relationship of dependence/employment with the sponsor or the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A, Interventional group	Atropine eye drops, 0.02%	Treatment period 1: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 3: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months
Arm A, Interventional group	Placebo (NaCl 0.9%) eye drops	Treatment period 1: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.02%, 1 drop/eye, daily for 12 months Treatment period 3: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months
Arm B, Control group	Atropine eye drops, 0.01%	Treatment period 1: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months Treatment period 3: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months
Arm B, Control group	Placebo (NaCl 0.9%) eye drops	Treatment period 1: Placebo (NaCl 0.9%) eye drops, 1 drop/eye, daily for 12 months Treatment period 2: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months Treatment period 3: Atropine eye drops, 0.01%, 1 drop/eye, daily for 12 months

Primary Outcome Measures

Name	Time	Method
Demonstration of superiority of low-dose atropine 0.02% eye drops compared to placebo for myopia control	Baseline - 12 months	Change in cycloplegic refraction \[dioptre (D)/year\] after one year will be performed using an analysis of covariance (ANCOVA) model with the annual change in refraction as the dependent variable. The mean value of both eyes is analysed.

Secondary Outcome Measures

Name	Time	Method
Assessment of axial eye length growth under low-dose atropine 0.02% in comparison to placebo	Baseline - 12 months	Change in axial length \[mm/year\]. The mean value of both eyes is analysed. Analyses will be performed in a regression model.
Assessment of the categorized rate of change in refraction of low-dose atropine 0.02% compared to placebo	Baseline - 12 months	The primary endpoint change in cycloplegic refraction after one year will be categorized (patients progressing \< 0.25D (dioptre), 0.25D - 0.75D and \> 0.75D after one year of treatment) and will be analysed descriptively, giving absolute and relative frequencies of these categories as a supportive analysis.

Trial Locations

Locations (19)

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Augen-Zentrum-Nordwest, Augenpraxis Ahaus; 🇩🇪 Ahaus, Germany

Universitäts-Augenklinik Bonn; 🇩🇪 Bonn, Germany

Universitätsklinikum Erlangen, Augenklinik; 🇩🇪 Erlangen, Germany

Universitätsklinikum Essen, Klinik für Augenheilkunde; 🇩🇪 Essen, Germany

Medical Center - University of Freiburg, Eye Hospital; 🇩🇪 Freiburg, Germany

Universitätsmedizin Göttingen, Augenklinik; 🇩🇪 Göttingen, Germany

Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Augenheilkunde; 🇩🇪 Hamburg, Germany

Medizinische Hochschule Hannover, Klinik für Augenheilkunde; 🇩🇪 Hannover, Germany

Universitätsklinikum Heidelberg, Augenklinik; 🇩🇪 Heidelberg, Germany

Uniklinik Köln, Zentrum für Augenheilkunde; 🇩🇪 Köln, Germany

Universitätsklinikum Leipzig, Klinik und Poliklinik für Augenheilkunde; 🇩🇪 Leipzig, Germany

Universitätsklinikum Magdeburg A.ö.R., Universitätsaugenklinik; 🇩🇪 Magdeburg, Germany

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Augenklinik und Poliklinik; 🇩🇪 Mainz, Germany

Ludwig-Maximilians-Universität München, Augenklinik und Poliklinik; 🇩🇪 München, Germany

Klinik für Augenheilkunde des UKM, Gebäude D15; 🇩🇪 Münster, Germany

Pius-Hospital Oldenburg, Medizinischer Campus Universität Oldenburg, Universitätsklinik für Augenheilkunde; 🇩🇪 Oldenburg, Germany

AugenCentrum Rosenheim; 🇩🇪 Rosenheim, Germany

Universitätsklinikum Ulm, Klinik für Augenheilkunde; 🇩🇪 Ulm, Germany