Myopia
Conditions
Keywords
Myopia, atropine
Brief summary
Study Objectives The objectives for this randomized trial are: 1. To determine the efficacy of daily low-dose atropine (0.01%) for slowing myopia progression over a two-year treatment period in children aged 5 to less than 13 years (Primary Outcome On-Treatment). 2. To determine the efficacy of atropine treatment on myopia progression 6 months following cessation of low-dose atropine treatment (Secondary Outcome Off-Treatment). Synopsis of Study Design The current study is designed as an efficacy study, making effort to maximize adherence to treatment group assignments. After a run-in phase during which all participants are treated with daily artificial tear eyedrops for 2-4 weeks (and glasses are updated if required) to assess their ability to adhere to daily eye drops, participants are randomly assigned to daily atropine or placebo for 24 months, followed by 6 months off treatment.
Detailed description
Study Objectives The objectives for this randomized trial are: 1. To determine the efficacy of daily low-dose atropine (0.01%) for slowing myopia progression over a two-year treatment period in children aged 5 to less than 13 years with myopia -1.00 to -6.00D at the time of enrollment (Primary Outcome On-Treatment). 2. To determine the efficacy of atropine treatment on myopia progression 6 months following cessation of low-dose atropine treatment (Secondary Outcome Off-Treatment). Synopsis of Study Design The current study is designed as an efficacy study, making effort to maximize adherence to treatment group assignments. After a run-in phase during which all participants are treated with daily artificial tear eyedrops for 2-4 weeks (and glasses are updated if required) to assess their ability to adhere to daily eye drops, participants are randomly assigned to daily atropine or placebo for 24 months, followed by 6 months off treatment.
Interventions
DRUGAtropine
Daily 0.01% atropine eyedrops
OTHERPlacebo Eyedrops
Daily placebo eyedrops
Sponsors
Jaeb Center for Health Research
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Cycloplegic autorefraction, axial length, and additional biometry will be measured by a masked examiner at all follow-up visits using the same instrumentation on the participant throughout the study. Masking will be accomplished by having site personnel administer cyclopentolate to both eyes of each participant and wait 30 minutes before he/she sees the masked examiner. The masked examiner may be a technician or an investigator and must be certified to complete these measurements. Parents, patients, and investigators are also masked to treatment.
Intervention model description
The current study is designed as an efficacy study, making effort to maximize adherence to treatment group assignments. After a run-in phase during which all participants are treated with daily artificial tear eyedrops for 2-4 weeks (and glasses are updated if required) to assess their ability to adhere to daily eye drops, participants are randomly assigned to daily atropine or placebo for 24 months, followed by 6 months off treatment.
Eligibility
Sex/Gender
ALL
Age
5 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Age 5 years to \<13 years at time of enrollment. Children within 4 weeks of their 13th birthday are not eligible. * Refractive error meeting the following by cycloplegic autorefraction: * Myopia -1.00D to -6.00D spherical equivalent (SE) in both eyes * Astigmatism \<=1.50D in both eyes * Anisometropia \<1.00D SE * Gestational age ≥ 32 weeks. * Birth weight \>1500g. * Parent understands the protocol and is willing to accept randomization to atropine or placebo. * Is willing to participate in a 2 to 4 week run-in phase using daily artificial tear eyedrops. * Able to return in 2 to 4 weeks for possible randomization. * Parent has a phone (or access to phone) and is willing to be contacted by Investigator's site staff. * Relocation outside of the area of an active PEDIG site within next 32 months is not anticipated.
Exclusion criteria
* Current or previous myopia treatment with atropine, pirenzepine or other anti-muscarinic agent. * Current or previous use of bifocals, progressive-addition lenses, or multi-focal contact lenses. * Current or previous use of orthoK, rigid gas permeable, or other contact lenses being used to reduce myopia progression. * Known atropine allergy. * Abnormality of the cornea, lens, central retina, iris or ciliary body. * Current or prior history of manifest strabismus, amblyopia, or nystagmus. * Prior eyelid, strabismus, intraocular, or refractive surgery. * Down syndrome or cerebral palsy. * Females who are pregnant, lactating, or intending to become pregnant within the next 30 months. * A negative urine pregnancy test will be required for all females who have experienced menarche.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | At 24 months | 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. |
| Primary Outcome Measure Stratified by Sex | at 24 months | NIH-required analysis. Primary outcome measure (stratified by sex): 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. |
| Primary Outcome Measure Stratified by Race | by 24 months | NIH-required analysis. Primary outcome measure (stratified by race): 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. |
| Primary Outcome Measure Stratified by Ethnicity | at 24 months | NIH-required analysis. Primary outcome measure (stratified by ethnicity): 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. |
| Primary Outcome: Mean Change in Spherical Equivalent Refractive Error at 24 Months | 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | 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. |
Countries
United States
Contacts
STUDY_CHAIRMichael X Repka, MD, MBA
Wilmer Eye Institute
STUDY_CHAIRKatherine K Weise, OD, MBA
University of Alabama Birmingham Pediatric Eye Care, Birmingham Health Care
Participant flow
Pre-assignment details
Two hundred patients were enrolled into the run-in phase; 13 were ineligible for randomization
Participants by arm
| Arm | Count |
|---|---|
| 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 | 125 |
| 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 | 62 |
| Total | 187 |
Baseline characteristics
| Characteristic | Total | Placebo Group | Atropine Group |
|---|---|---|---|
| Age, Continuous | 10.1 years STANDARD_DEVIATION 1.8 | 10.1 years STANDARD_DEVIATION 1.8 | 10.1 years STANDARD_DEVIATION 1.8 |
| Age, Customized 11 to <13 years | 67 Participants | 26 Participants | 41 Participants |
| Age, Customized 5 to <7 years | 9 Participants | 3 Participants | 6 Participants |
| Age, Customized 7 to <9 years | 41 Participants | 13 Participants | 28 Participants |
| Age, Customized 9 to <11 years | 70 Participants | 20 Participants | 50 Participants |
| Current Refractive Correction (Single-vision Spectacles or Contact Lenses) No | 1 Participants | 1 Participants | 0 Participants |
| Current Refractive Correction (Single-vision Spectacles or Contact Lenses) Yes | 186 Participants | 61 Participants | 125 Participants |
| Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) 0.0 to < 0.1 logMAR | 52 Participants | 16 Participants | 36 Participants |
| Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) -0.1 to < 0.0 logMAR | 97 Participants | 35 Participants | 62 Participants |
| Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) 0.1 to < 0.2 logMAR | 14 Participants | 5 Participants | 9 Participants |
| Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) <-0.2 logMAR | 1 Participants | 1 Participants | 0 Participants |
| Distance Visual Acuity in Habitual Refractive Correction (Mean of Both Eyes) -0.2 to < -0.1 logMAR | 23 Participants | 5 Participants | 18 Participants |
| Eye Color Brown | 123 Participants | 41 Participants | 82 Participants |
| Eye Color Not Brown | 64 Participants | 21 Participants | 43 Participants |
| Mean OD and OS Anterior Chamber Depth | 3.9 millimeter STANDARD_DEVIATION 0.2 | 3.9 millimeter STANDARD_DEVIATION 0.2 | 3.8 millimeter STANDARD_DEVIATION 0.2 |
| Mean OD and OS Flat Corneal Radius | 43.4 Diopters squared STANDARD_DEVIATION 1.4 | 43.6 Diopters squared STANDARD_DEVIATION 1.4 | 43.4 Diopters squared STANDARD_DEVIATION 1.4 |
| Mean OD and OS Lens Thickness | 3.3 millimeters cubed STANDARD_DEVIATION 0.2 | 3.3 millimeters cubed STANDARD_DEVIATION 0.2 | 3.4 millimeters cubed STANDARD_DEVIATION 0.2 |
| Number of Biological Parents with Myopia 0 | 27 Participants | 11 Participants | 16 Participants |
| Number of Biological Parents with Myopia 1 | 75 Participants | 24 Participants | 51 Participants |
| Number of Biological Parents with Myopia 2 | 72 Participants | 20 Participants | 52 Participants |
| Number of Biological Parents with Myopia Myopia history unknown for one or both parents | 13 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Black | 34 Participants | 14 Participants | 20 Participants |
| Race/Ethnicity, Customized East Asian | 20 Participants | 4 Participants | 16 Participants |
| Race/Ethnicity, Customized More Than one race | 11 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized West Asian / South Asian | 6 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White Hispanic or Latino | 30 Participants | 9 Participants | 21 Participants |
| Race/Ethnicity, Customized White (not Hispanic or Latino) | 86 Participants | 28 Participants | 58 Participants |
| Sex: Female, Male Female | 101 Participants | 36 Participants | 65 Participants |
| Sex: Female, Male Male | 86 Participants | 26 Participants | 60 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 125 | 0 / 62 |
| other Total, other adverse events | 109 / 125 | 56 / 62 |
| serious Total, serious adverse events | 2 / 125 | 0 / 62 |
Outcome results
Primary
Treatment Group Comparison of Change in Spherical Equivalent Refractive Error.
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.
Time frame: At 24 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-3.50 to -3.00 Diopters | 1 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-1.50 to -1.00 Diopters | 19 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-2.50 to -2.00 Diopters | 5 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-1.00 to -0.50 Diopters | 37 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-3.00 to -2.50 Diopters | 1 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-0.50 to 0.00 Diopters | 46 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-2.00 to -1.50 Diopters | 8 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >0 Diopters | 2 Participants |
| Atropine Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | <=-3.50 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >0 Diopters | 4 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | <=-3.50 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-3.50 to -3.00 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-3.00 to -2.50 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-2.50 to -2.00 Diopters | 2 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-2.00 to -1.50 Diopters | 7 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-1.50 to -1.00 Diopters | 9 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-1.00 to -0.50 Diopters | 18 Participants |
| Placebo Group | Treatment Group Comparison of Change in Spherical Equivalent Refractive Error. | >-0.50 to 0.00 Diopters | 18 Participants |
Comparison: Null Hypothesis: no difference in mean change in SER from baseline to 24 months between the atropine and placebo groups95% CI: [-0.19, 0.15]
Secondary
Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent
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.
Time frame: At 30 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-2.00 to -1.50 Diopters | 8 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-1.50 to -1.00 Diopters | 22 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-3.00 to -2.50 Diopters | 5 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-1.00 to -0.50 Diopters | 35 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-3.50 to -3.00 Diopters | 2 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-0.50 to 0.00 Diopters | 36 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-2.50 to -2.00 Diopters | 5 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >0 Diopters | 4 Participants |
| Atropine Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | <=-3.50 Diopters | 1 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >0 Diopters | 3 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | <=-3.50 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-3.50 to -3.00 Diopters | 1 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-3.00 to -2.50 Diopters | 0 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-2.50 to -2.00 Diopters | 3 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-1.50 to -1.00 Diopters | 11 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-1.00 to -0.50 Diopters | 20 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-0.50 to 0.00 Diopters | 13 Participants |
| Placebo Group | Treatment Group Comparison of Change From Baseline to 30 Months in Spherical Equivalent | >-2.00 to -1.50 Diopters | 6 Participants |
Comparison: Null Hypothesis: no difference in mean change in SER from baseline to 24 months between the atropine and placebo groups95% CI: [-0.25, 0.17]