MAD Trial: Myopia Atropine Dose

Progressive Myopia Clinical Trial

— MAD  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05667454
• Other study ID #: NL78526.078.21
• Secondary ID: MEC-2021-0814202
• Status: Recruiting
• Phase: Phase 3
• Start date: December 19, 2022
• Est. completion date: December 1, 2028

Study information

• Verified date: February 2024
• Source: Erasmus Medical Center
• Contact: Jan Roelof Polling, Dr.
• Phone: +31628449254
• Email: j.polling[@]erasmusmc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 550
• Est. completion date: December 1, 2028
• Est. primary completion date: December 1, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 11 Years

Eligibility

Inclusion Criteria:

• Children aged 6 to = 11 years with bilateral myopia
• Onset of myopia = 4 years of age
• History of progression = -0.5D/yr.
• SER of at least -1.50D 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.

Related Conditions & MeSH terms

• Myopia
• Myopia, Degenerative
• Progressive Myopia

Intervention

Drug:
• Atropine Ophthalmic 0.05%
Atropine 0.05% sulphate ophthalmic solution
• Atropine Ophthalmic 0.5%
Atropine 0.5% sulphate ophthalmic solution

Locations

Country	Name	City	State
Netherlands	Noordwest Ziekenhuisgroep	Alkmaar
Netherlands	Flevoziekenhuis	Almere
Netherlands	OLVG, locatie Oost	Amsterdam
Netherlands	Ophthalmologistenpraktijk Delfland	Delft
Netherlands	Reinier de Graaf Gasthuis	Delft
Netherlands	Bergman Clinics - Den Bosch	Den Bosch
Netherlands	Haga Ziekenhuis	Den Haag
Netherlands	Oogkliniek Den Haag	Den Haag
Netherlands	Deventer Ziekenhuis	Deventer
Netherlands	Albert Schweitzer ziekenhuis	Dordrecht
Netherlands	Bergman Clinics - Ede	Ede
Netherlands	Admiraal de Ruyter Ziekenhuis	Goes
Netherlands	Tjongerschans Heerenveen	Heerenveen
Netherlands	Oogcentrum Noordholland	Heerhugowaard
Netherlands	Isala - Kampen	Kampen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Bergman Clinics - Lelystad	Lelystad
Netherlands	Isala - Meppel	Meppel
Netherlands	St. Antonius	Nieuwegein
Netherlands	Radboudumc	Nijmegen
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	Ziekenhuis Rivierenland Tiel	Tiel
Netherlands	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	Isala - Zwolle	Zwolle

Sponsors (2)

Lead Sponsor	Collaborator
Erasmus Medical Center	ZonMw: The Netherlands Organisation for Health Research and Development

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression of axial length in mm from baseline to t = 36 months.		3 years
Secondary	Progression of axial length in mm from baseline to t = 60 months.		5 years
Secondary	Progression of spherical equivalent of refraction in dioptres from baseline to t = 36 months. compared to atropine 0.5% treatment.		3 years
Secondary	Progression of spherical equivalent of refraction in dioptres from baseline to t = 60		5 years
Secondary	Proportion of subjects who show = 0.20 mm (good response); 0.2 - 0.3 mm (acceptable response), and > 3 mm (nonresponse)		3 years
Secondary	Proportion of subjects who progressed to high myopia (AL 26+ mm)		3 years
Secondary	Change in visual function (BCVA, contrast sensitivity, and glare)		3 years
Secondary	Frequency and type of treatment-related (serious) adverse events as assessed by CTCAE v5.0 (=safety)		3 years
Secondary	Proportion of non-adherence		3 years
Secondary	Difference in health related quality of life		5 years