Trial Outcomes & Findings for Low-Dose Atropine for Treatment of Myopia (NCT NCT03334253)

Last Updated: 2023-09-05

Results Overview

The primary analysis will be a treatment group comparison of change from baseline to 24-months in spherical equivalent refractive error (SER), as measured by a masked examiner using cycloplegic autorefraction (on-treatment comparison). The mean of the three readings from autorefraction in each eye will be calculated and then the mean of both eyes for each participant will be used for the analysis. The treatment group difference (atropine - placebo) and a 95% confidence interval will be calculated based on the model estimates at 24 months.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

200 participants

Primary outcome timeframe

At 24 months

Results posted on

2023-09-05

Participant Flow

Two hundred patients were enrolled into the run-in phase; 13 were ineligible for randomization

Participant milestones

Participant milestones
Measure	Atropine Group 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
Overall Study STARTED	125	62
Overall Study COMPLETED	118	57
Overall Study NOT COMPLETED	7	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Atropine Group 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
Overall Study Withdrawal by Subject	1	0
Overall Study Lost to Follow-up	4	3
Overall Study Moved residence	2	2

Baseline Characteristics

Flat corneal radius was not available for 1 patient in the placebo group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atropine Group n=125 Participants 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group n=62 Participants Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops	Total n=187 Participants Total of all reporting groups
Age, Continuous	10.1 years STANDARD_DEVIATION 1.8 • n=125 Participants	10.1 years STANDARD_DEVIATION 1.8 • n=62 Participants	10.1 years STANDARD_DEVIATION 1.8 • n=187 Participants
Age, Customized 5 to <7 years	6 Participants n=125 Participants	3 Participants n=62 Participants	9 Participants n=187 Participants
Age, Customized 7 to <9 years	28 Participants n=125 Participants	13 Participants n=62 Participants	41 Participants n=187 Participants
Age, Customized 9 to <11 years	50 Participants n=125 Participants	20 Participants n=62 Participants	70 Participants n=187 Participants
Age, Customized 11 to <13 years	41 Participants n=125 Participants	26 Participants n=62 Participants	67 Participants n=187 Participants
Sex: Female, Male Female	65 Participants n=125 Participants	36 Participants n=62 Participants	101 Participants n=187 Participants
Sex: Female, Male Male	60 Participants n=125 Participants	26 Participants n=62 Participants	86 Participants n=187 Participants
Race/Ethnicity, Customized White (not Hispanic or Latino)	58 Participants n=125 Participants	28 Participants n=62 Participants	86 Participants n=187 Participants
Race/Ethnicity, Customized White Hispanic or Latino	21 Participants n=125 Participants	9 Participants n=62 Participants	30 Participants n=187 Participants
Race/Ethnicity, Customized Black	20 Participants n=125 Participants	14 Participants n=62 Participants	34 Participants n=187 Participants
Race/Ethnicity, Customized East Asian	16 Participants n=125 Participants	4 Participants n=62 Participants	20 Participants n=187 Participants
Race/Ethnicity, Customized West Asian / South Asian	4 Participants n=125 Participants	2 Participants n=62 Participants	6 Participants n=187 Participants
Race/Ethnicity, Customized More Than one race	6 Participants n=125 Participants	5 Participants n=62 Participants	11 Participants n=187 Participants
Eye Color Brown	82 Participants n=125 Participants	41 Participants n=62 Participants	123 Participants n=187 Participants
Eye Color Not Brown	43 Participants n=125 Participants	21 Participants n=62 Participants	64 Participants n=187 Participants
Number of Biological Parents with Myopia 0	16 Participants n=125 Participants	11 Participants n=62 Participants	27 Participants n=187 Participants
Number of Biological Parents with Myopia 1	51 Participants n=125 Participants	24 Participants n=62 Participants	75 Participants n=187 Participants
Number of Biological Parents with Myopia 2	52 Participants n=125 Participants	20 Participants n=62 Participants	72 Participants n=187 Participants
Number of Biological Parents with Myopia Myopia history unknown for one or both parents	6 Participants n=125 Participants	7 Participants n=62 Participants	13 Participants n=187 Participants
Current Refractive Correction (Single-vision Spectacles or Contact Lenses) Yes	125 Participants n=125 Participants	61 Participants n=62 Participants	186 Participants n=187 Participants
Current Refractive Correction (Single-vision Spectacles or Contact Lenses) No	0 Participants n=125 Participants	1 Participants n=62 Participants	1 Participants n=187 Participants
Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) <-0.2 logMAR	0 Participants n=125 Participants	1 Participants n=62 Participants	1 Participants n=187 Participants
Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) -0.2 to < -0.1 logMAR	18 Participants n=125 Participants	5 Participants n=62 Participants	23 Participants n=187 Participants
Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) -0.1 to < 0.0 logMAR	62 Participants n=125 Participants	35 Participants n=62 Participants	97 Participants n=187 Participants
Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) 0.0 to < 0.1 logMAR	36 Participants n=125 Participants	16 Participants n=62 Participants	52 Participants n=187 Participants
Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) 0.1 to < 0.2 logMAR	9 Participants n=125 Participants	5 Participants n=62 Participants	14 Participants n=187 Participants
Mean OD and OS Flat Corneal Radius	43.4 Diopters squared STANDARD_DEVIATION 1.4 • n=125 Participants • Flat corneal radius was not available for 1 patient in the placebo group.	43.6 Diopters squared STANDARD_DEVIATION 1.4 • n=61 Participants • Flat corneal radius was not available for 1 patient in the placebo group.	43.4 Diopters squared STANDARD_DEVIATION 1.4 • n=186 Participants • Flat corneal radius was not available for 1 patient in the placebo group.
Mean OD and OS Anterior Chamber Depth	3.8 millimeter STANDARD_DEVIATION 0.2 • n=125 Participants	3.9 millimeter STANDARD_DEVIATION 0.2 • n=62 Participants	3.9 millimeter STANDARD_DEVIATION 0.2 • n=187 Participants
Mean OD and OS Lens Thickness	3.4 millimeters cubed STANDARD_DEVIATION 0.2 • n=72 Participants • Lens thickness was not available for some patients (N=53 in atropine and N=27 in placebo) because the biometer used did not provide a lens thickness reading due to measurement difficulty.	3.3 millimeters cubed STANDARD_DEVIATION 0.2 • n=35 Participants • Lens thickness was not available for some patients (N=53 in atropine and N=27 in placebo) because the biometer used did not provide a lens thickness reading due to measurement difficulty.	3.3 millimeters cubed STANDARD_DEVIATION 0.2 • n=107 Participants • Lens thickness was not available for some patients (N=53 in atropine and N=27 in placebo) because the biometer used did not provide a lens thickness reading due to measurement difficulty.

PRIMARY outcome

Timeframe: At 24 months

Outcome measures

Outcome measures
Measure	Atropine Group n=119 Participants 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group n=58 Participants Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. <=-3.50 Diopters	0 Participants	0 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-3.50 to -3.00 Diopters	1 Participants	0 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-3.00 to -2.50 Diopters	1 Participants	0 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-2.50 to -2.00 Diopters	5 Participants	2 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-2.00 to -1.50 Diopters	8 Participants	7 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-1.50 to -1.00 Diopters	19 Participants	9 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-1.00 to -0.50 Diopters	37 Participants	18 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >-0.50 to 0.00 Diopters	46 Participants	18 Participants
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. >0 Diopters	2 Participants	4 Participants

SECONDARY outcome

Timeframe: At 30 months

Treatment group comparison of change from baseline to 30 months in spherical equivalent in each eye as measured by a masked examiner using cycloplegic autorefraction (off-treatment comparison). Calculated based on the model estimates at 24 months.

Outcome measures

Outcome measures
Measure	Atropine Group n=118 Participants 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group n=57 Participants Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-1.50 to -1.00 Diopters	22 Participants	11 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent <=-3.50 Diopters	1 Participants	0 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-3.50 to -3.00 Diopters	2 Participants	1 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-3.00 to -2.50 Diopters	5 Participants	0 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-2.50 to -2.00 Diopters	5 Participants	3 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-2.00 to -1.50 Diopters	8 Participants	6 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-1.00 to -0.50 Diopters	35 Participants	20 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >-0.50 to 0.00 Diopters	36 Participants	13 Participants
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent >0 Diopters	4 Participants	3 Participants

Adverse Events

Atropine Group

Serious events: 2 serious events

Other events: 109 other events

Deaths: 0 deaths

Placebo Group

Serious events: 0 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Atropine Group n=125 participants at risk 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group n=62 participants at risk Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
General disorders Hospitalization	1.6% 2/125 • Number of events 2 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.

Other adverse events

Additional Information

Raymond Kraker, PEDIG Coordinating Center Director

Jaeb Center for Health Research

Phone: 8139758690

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Atropine Group n=125 participants at risk 0.01% atropine eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off atropine eyedrops Atropine: Daily 0.01% atropine eyedrops	Placebo Group n=62 participants at risk Placebo eyedrops administered 1 drop to each eye daily in each eye for 24 months, followed by 6 months off placebo eyedrops Placebo Eyedrops: Daily placebo eyedrops
Eye disorders Eye Irritiation	72.0% 90/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	82.3% 51/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Photophobia	25.6% 32/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	27.4% 17/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Vision Blurred	13.6% 17/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	16.1% 10/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Allergic Conjunctivitis	8.0% 10/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	8.1% 5/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Ocular Discomfort	6.4% 8/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	8.1% 5/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Visual Impairment	4.8% 6/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	3.2% 2/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Blepharitis	4.8% 6/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Meibomian gland dysfunction	2.4% 3/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	4.8% 3/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Eye Pain	7.2% 9/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Dry Eye	2.4% 3/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Hordeolum	1.6% 2/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	3.2% 2/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Accommodation Disorder	2.4% 3/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Optic Disc Drusen	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Headache	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Visual Acuity Reduced	1.6% 2/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Vitreous Floaters	1.6% 2/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Eye injury	0.00% 0/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	3.2% 2/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Ocular hyperaemia	1.6% 2/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Retinal degeneration	1.6% 2/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Ulcerative keratitis	0.00% 0/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Foreign body in eye	0.00% 0/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Meibomianitis	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Conjunctival hyperaemia	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Dermatitis contact	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Diplopia	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Pruritus	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Lacrimation increased	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Conjunctivitis	0.00% 0/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Chalazion	0.00% 0/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	1.6% 1/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Mydriasis	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.
Eye disorders Corneal Scar	0.80% 1/125 • Adverse event data was collected for the duration of the study, baseline to 30 months.	0.00% 0/62 • Adverse event data was collected for the duration of the study, baseline to 30 months.