Clinical trial NCT05667454: MAD Trial: Myopia Atropine Dose
Official title: Investigator Led, Double-masked, Multicenter, Randomized Clinical Trial for the Comparison of Atropine 0.5% Versus Atropine 0.05% Eye Drops for the Prevention of Myopia Progression in Dutch Children
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Progressive Myopia
Keywords: Myopia
Atropine
Axial length
Child
Lead sponsor: Erasmus Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2022-12-28
Enrollment: 550
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this interventional study is to compare the efficacy of Atropine 0.05% to Atropine 0.5% treatment against progression of axial length in European children with progressive myopia, and to evaluate the safety, adherence, and reasons for nonresponse. Subjects will use Atropine eye drops for a period of 3 years, followed by a 2 year observational period.

Detailed description: With the current worldwide myopia boom the frequency of high myopia will also increase, and potentially blinding complications such as myopic macular degeneration, retinal detachment, and glaucoma will occur more often. In the Netherlands high myopia will become the most important cause of low vision and blindness by 2050. As treatment options are limited once the eye is fully grown, prevention of a long axial length at childhood is the only way to counteract this prospect. Pharmacological interventions have shown a high efficacy in stopping eye growth, in particular eye drops with high dose Atropine (0.5%, 1%). Nevertheless, the high frequency of side effects (photophobia, reading problems) of these Atropine concentrations has favoured the use of low dose Atropine. Atropine 0.01% is the most commonly used and lowest dosage; it has shown stability of refractive error, but not of axial length. Recent studies have shown that Atropine 0.05% has low risk of side effects, but a higher efficacy than 0.01%. Many ongoing trials are now comparing various low dose Atropine to placebo, but none are comparing the highest low dose to the lowest high dose Atropine.

Eligibility criteria: Inclusion Criteria:

* Children aged 6 to ≤ 11 years with bilateral myopia
* Onset of myopia ≥ 4 years of age
* History of progression
* SER of at least -1.00D and no greater than -6.00D in each eye measured using cycloplegic auto refraction
* Intraocular pressure \< 21 mm Hg in each eye
* Distance vision correctable to at least 0.1 Log MAR (logarithm of the minimum angle of resolution) in each eye

Exclusion Criteria:

* Allergy to atropine or other excipients of the eye drops
* History of amblyopia or strabismus
* History of retinal dystrophy or systemic disorder
* Abnormal ocular biometry aside from axial length
* History of glaucoma
* Chronic use of topical or systemic antimuscarinic/anticholinergic medications in the 21 days prior to screening, and/or anticipated need for chronic use over the duration of the study (i.e., more than 7 consecutive days in 1 month or more than a total of 30 days in 1 year).
* Chronic use (more than 3 days a week) of topical ophthalmological medication (prescribed or over the counter) other than the assigned study medication. The use of artificial tears is allowed but not in the 1 hour before or after the administration of the study medication.
* The anticipated need to use chronic ophthalmic or systemic oral corticosteroids during the study. (i.e., \< 2 weeks)
* Prior myopia treatments.
* Employees of the study center and their family members.

Primary outcomes:
measure: Progression of axial length in mm from baseline to t = 36 months.
timeFrame: 3 years
Secondary outcomes:
measure: Progression of axial length in mm from baseline to t = 60 months.
timeFrame: 5 years
measure: Progression of spherical equivalent of refraction in dioptres from baseline to t = 36 months. compared to atropine 0.5% treatment.
timeFrame: 3 years
measure: Progression of spherical equivalent of refraction in dioptres from baseline to t = 60
timeFrame: 5 years
measure: Proportion of subjects who show ≤ 0.20 mm (good response); 0.2 - 0.3 mm (acceptable response), and > 3 mm (nonresponse)
timeFrame: 3 years
measure: Proportion of subjects who progressed to high myopia (AL 26+ mm)
timeFrame: 3 years
measure: Change in visual function (BCVA, contrast sensitivity, and glare)
timeFrame: 3 years
measure: Frequency and type of treatment-related (serious) adverse events as assessed by CTCAE v5.0 (=safety)
timeFrame: 3 years
measure: Proportion of non-adherence
timeFrame: 3 years
measure: Difference in health related quality of life
timeFrame: 5 years
Other outcomes:
Locations:
city: Almere
country: Netherlands
facility: Flevoziekenhuis
city: Amsterdam
country: Netherlands
facility: OLVG, locatie Oost
city: Delft
country: Netherlands
facility: Ophthalmologistenpraktijk Delfland
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Den Haag
country: Netherlands
facility: Oogkliniek Den Haag
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer ziekenhuis
city: Ede
country: Netherlands
facility: Bergman Clinics - Ede
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Ziekenhuis
city: Heerenveen
country: Netherlands
facility: Frisius MC
city: Heerhugowaard
country: Netherlands
facility: Oogcentrum Noordholland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Lelystad
country: Netherlands
facility: Bergman Clinics - Lelystad
city: Maastricht
country: Netherlands
facility: Maastricht UMC+
city: Nieuwegein
country: Netherlands
facility: St. Antonius
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Tiel
country: Netherlands
facility: Ziekenhuis Rivierenland Tiel
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Ziekenhuis
Study officials:
affiliation: EMC
name: C.C.W. Klaver, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: