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Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old (ATS16)

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT00944710
First received: July 21, 2009
Last updated: October 22, 2014
Last verified: October 2014
  Purpose

This study is designed to evaluate the effectiveness of adding a plano lens to weekend atropine after visual acuity has stabilized with weekend atropine but amblyopia is still present. Children ages 3 to <8 years with visual acuity of 20/50 to 20/400 in the amblyopic eye will be enrolled in a run-in phase with weekend atropine until no improvement, followed by randomization of eligible patients to weekend atropine treatment with a plano lens over the sound eye versus without a plano lens over the sound eye. The primary objective is to determine if adding a plano lens to weekend atropine will improve visual acuity in patients with amblyopia still present after visual acuity has stabilized with initial treatment.


Condition Intervention Phase
Amblyopia
Drug: Atropine
Device: Plano lens
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Augmenting Atropine Treatment for Amblyopia in Children 3 to < 8 Years Old

Resource links provided by NLM:


Further study details as provided by Jaeb Center for Health Research:

Primary Outcome Measures:
  • Distribution of 10-week Amblyopic-Eye Visual Acuity [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]

    The masked 10-week amblyopic eye visual acuity scores were tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.


  • Mean 10-week Amblyopic-Eye Visual Acuity [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]

    The primary outcome analysis was a treatment group comparison of the masked 10-week amblyopic eye visual acuity using an analysis of covariance (ANCOVA) model, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.


  • Distribution of the Change in Amblyopic-Eye Visual Acuity [ Time Frame: Randomization to 10 weeks ] [ Designated as safety issue: No ]

    The change in 10-week amblyopic eye visual acuity scores since randomization was tabulated for both treatment groups, and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.


  • Mean Change in Amblyopic-Eye Visual Acuity at 10 Weeks From Randomization [ Time Frame: Randomization to 10 weeks ] [ Designated as safety issue: No ]

    The change in 10-week amblyopic eye visual acuity was computed for both treatment groups and included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) with no imputation for missing data.

    The primary outcome analysis followed the "intent-to-treat" principle. Therefore, data from randomized participants were included in the analysis regardless of whether the assigned treatment was actually received or whether they deviated from treatment against protocol. In addition, randomized participants who were found to be ineligible upon subsequent review of enrollment data were included in the primary outcome analysis.



Secondary Outcome Measures:
  • Treatment Group Comparison of the Proportion of Participants Who Achieved 20/25 or Better Visual Acuity at 10 Weeks Since Randomization [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]

    The proportion of participants who achieved 20/25 or better visual acuity since randomization was computed at the 10-week outcome.

    The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity was 20/25 or better since randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.


  • Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines at 10 Weeks Since Randomization [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]

    The proportion of participants who improved at least 2 logMAR lines since randomization was computed at the 10-week outcome.

    The secondary outcome analysis was a treatment group comparison of the proportion of participants whose 10-week masked amblyopic eye visual acuity improved at least 2 logMAR lines since randomization using logistic regression, adjusting for visual acuity at randomization. The analysis included data from 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.


  • Spectacle Compliance at 10 Weeks by Treatment Group [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]
    The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

  • Average Spectacle Compliance by Treatment Group [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

  • Atropine Compliance at 10 Weeks by Treatment Group [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]
    The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

  • Average Atropine Compliance by Treatment Group [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    The distribution of compliance with prescribed treatment was tabulated for the 10-week outcome and as averaged scores across all study follow-up visits. Compliance was evaluated as excellent (>75%), good (51%-75%), fair (26%-50%), or poor (<26%) based on discussions with the parent and by reviewing study calendars maintained by the parent, who recorded the frequency of atropine administration.

  • Distribution of Interocular Difference at 12-week Exam [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
    Distribution of Interocular Difference Between Eyes at 12-week Exam

  • Mean Interocular Difference at 12-week Exam [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
    Mean Interocular Difference Between Eyes at 12-week Exam

  • Distribution of 12-week Fellow-Eye Visual Acuity [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: Yes ]
    Following the 10-week primary outcome exam, participants discontinued the randomized treatment and returned 2 weeks later for a 12-week visit to measure off-treatment fellow-eye visual acuity.

  • Mean Fellow-Eye Visual Acuity at 12-week Exam [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: Yes ]
  • Distribution of Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: Yes ]
  • Mean Change in Fellow-Eye Visual Acuity at 12 Weeks From Randomization [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: Yes ]
  • Distribution of Baseline Characteristics at the 10-week Outcome [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]
    The number of participants was tabulated by treatment group within categorical levels of prespecified baseline subgroup factors for participants with 10-week visual acuity exams completed between 8 to 15 weeks (inclusive) according to principles specified in the primary outcome analysis.

  • Mean Amblyopic Eye Visual at Randomization According to Baseline Characteristics for 10-week Outcome [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]
    Mean amblyopic eye visual acuity at randomization was computed by treatment group within categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

  • Treatment Comparison of Mean Amblyopic Eye Visual Acuity Change at 10-weeks According to Baseline Characteristics [ Time Frame: 10 weeks after randomization ] [ Designated as safety issue: No ]
    A treatment comparison of mean amblyopic eye visual acuity change since randomization was performed at the 10-week outcome according to categorical levels of prespecified baseline subgroup factors. The analysis included data from participants with 10-week exams completed between 8 to 15 weeks (inclusive) according to the principles specified in the primary outcome analysis.

  • Distribution of Amblyopic-Eye Visual Acuity at Best Outcome Visit [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of best post-randomization (10 weeks or later) visual acuity scores in the amblyopic eye was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)

  • Mean Amblyopic-Eye Visual Acuity at Best Outcome Visit [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. A treatment comparison of mean amblyopic eye visual acuity at the visit of best post-randomization visual acuity (10 weeks or later) was performed using an analysis of covariance, adjusting for amblyopic eye visual acuity at randomization.

  • Distribution of Change in Amblyopic-Eye Visual Acuity From Randomization to Best Outcome Visit [ Time Frame: Randomization to 10 weeks or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The distribution of change in best post-randomization (10 weeks or later) visual acuity in the amblyopic eye since randomization was tabulated for both treatment groups using the initial visual acuity score (if a retest was obtained.)

  • Mean Change in Amblyopic-Eye Visual Acuity at Best Outcome Visit [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
    Participants in both groups who have improved by one or more lines from randomization to the 10-week outcome exam will continue in the study and visits will occur every 10 weeks until no improvement of one or more lines from the previous visit. The mean change in amblyopic eye visual acuity since randomization was computed for both treatment groups based on the visit of best post-randomization visual acuity (10 weeks or later) using the initial visual acuity score (if a retest was obtained.)

  • Treatment Group Comparison of the Proportion of Participants Who Have Improved by 2 or More logMAR Visual Acuity Lines Based on Visual Acuity at Best Outcome Visit [ Time Frame: 10 weeks after randomization or later (until no further VA improvement, up to maximum of 84 weeks for one subject) ] [ Designated as safety issue: No ]
  • Distribution of Randot Preschool Stereoacuity Score at 12 Weeks [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]
    Distribution of Randot Preschool Stereoacuity Score at 12 Weeks; Participants with a Randot Preschool test of >800 seconds of arc were classified as having a stereoacuity of 3000 seconds of arc if the Titmus fly test was positive or as nil if the Titmus fly test was negative.

  • Distribution of Randot Preschool Stereoacuity Scores at 12 Weeks for Participants With Anisometropic Amblyopia [ Time Frame: 12 weeks after randomization ] [ Designated as safety issue: No ]

Enrollment: 73
Study Start Date: August 2009
Study Completion Date: November 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intensified treatment
Weekend atropine 1% with plano lens over the sound eye
Drug: Atropine
Weekend atropine 1%
Other Name: Atropine
Device: Plano lens
plano lens over the sound eye
Active Comparator: Control
Weekend atropine 1%
Drug: Atropine
Weekend atropine 1%
Other Name: Atropine

Detailed Description:

Amblyopia is the most common cause of monocular visual impairment in both children and young and middle-aged adults. Both patching and atropine are accepted treatment modalities for the management of moderate amblyopia in children.1 Many practitioners prescribe weekend atropine as initial therapy for amblyopia. However, many children fail to achieve normal visual acuity in the amblyopic eye after treatment with this regimen. In a randomized trial conducted by PEDIG comparing atropine regimens, 58 of 83 patients with moderate amblyopia (70%) had amblyopic eye visual acuity of 20/32 or worse after 4 months of treatment with weekend atropine.2 In another PEDIG randomized trial comparing atropine with a plano lens versus without a plano lens for initial treatment of amblyopia, 60 of 84 patients with moderate amblyopia (71%) had amblyopic eye visual acuity of 20/32 or worse after 16 weeks of treatment with weekend atropine.3 When improvement stops after initial therapy and amblyopia is still present, treatment options include increasing the dosage of current treatment, switching to another treatment, maintaining the same treatment and dosage, or combining treatments. Many clinicians will add a plano lens over the sound eye to atropine treatment, in part because families using atropine have become comfortable with its use. This option is limited to children with hypermetropia in the sound eye. However, it is unknown whether adding a plano lens over the sound eye will improve amblyopic eye visual acuity more than continuing atropine alone in patients who have shown no improvement after initial treatment with atropine. In a PEDIG randomized trial comparing patching to atropine for initial treatment of amblyopia, a plano lens was prescribed for the sound eye for 55 patients who had not improved to 20/30 or at least 3 lines after 4 months of daily atropine use.1, 4 Their mean acuity improvement prior to using the plano lens was 1.0 line, compared with 1.6 lines after prescribing the plano lens. We are unaware of any reports of the response of treatment of amblyopia still present after initial treatment with weekend atropine.

  Eligibility

Ages Eligible for Study:   3 Years to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Major Eligibility Criteria for Run-in Phase

  • Age 3 to < 8 years
  • Amblyopia associated with strabismus, anisometropia, or both
  • Visual acuity in the amblyopic eye between 20/50 and 20/400 inclusive
  • Visual acuity in the sound eye 20/32 or better and inter-eye acuity difference >3 logMAR lines
  • Amblyopia treatment within the past 6 months subject to the following stipulations:

    • No more than 6 weeks of any amblyopia treatment other than spectacles (except for patients being treated with atropine who are entering the study on treatment)
    • No simultaneous treatment with patching and atropine
    • No use of atropine in combination with the sound eye spectacle lens reduced by more than 1.50 D
    • Maximum level of treatment within the past 6 months:

      • Patching: up to 2 hours daily
      • Atropine: up to once daily
  • Wearing spectacles with optimal correction (if amblyopic eye acuity is 20/80 or better, then VA must be stable in glasses; if amblyopic eye acuity is 20/100 or worse, then spectacles and atropine can be initiated simultaneously).
  • Hypermetropia and spectacle correction in sound eye of +1.50 D or more

Eligibility Criteria for Randomization:

  • Amblyopic eye acuity of 20/40 to 20/160 with an inter-ocular difference of >2 lines, or amblyopic eye acuity of 20/32 with 3 lines of IOD.
  • Compliance with weekend atropine treatment based on investigator judgment.

Exclusion Criteria:

  • Currently using vision therapy or orthoptics
  • Ocular cause for reduced visual acuity (nystagmus per se does not exclude the patient if the above visual acuity criteria are met)
  • Prior intraocular or refractive surgery
  • Known allergy to atropine or other cycloplegic drugs
  • Down Syndrome present
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00944710

Locations
United States, California
Southern California College of Optometry
Fullerton, California, United States, 92831
United States, North Carolina
Duke University Eye Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Jaeb Center for Health Research
Investigators
Study Chair: David K. Wallace, M.D. Duke University Eye Center
  More Information

No publications provided

Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT00944710     History of Changes
Other Study ID Numbers: NEI-144, 2U10EY011751
Study First Received: July 21, 2009
Results First Received: October 9, 2014
Last Updated: October 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Jaeb Center for Health Research:
Amblyopia
atropine
Plano lens

Additional relevant MeSH terms:
Amblyopia
Brain Diseases
Central Nervous System Diseases
Eye Diseases
Nervous System Diseases
Neurologic Manifestations
Sensation Disorders
Signs and Symptoms
Vision Disorders
Atropine
Adjuvants, Anesthesia
Anti-Arrhythmia Agents
Anti-Asthmatic Agents
Autonomic Agents
Bronchodilator Agents
Cardiovascular Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Mydriatics
Neurotransmitter Agents
Parasympatholytics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014