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Trial record 1 of 1 for:    IXT2
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Observation Versus Occlusion Therapy for Intermittent Exotropia (IXT2)

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ClinicalTrials.gov Identifier: NCT01032330
Recruitment Status : Completed
First Posted : December 15, 2009
Results First Posted : May 8, 2019
Last Update Posted : May 19, 2020
Sponsor:
Collaborators:
Pediatric Eye Disease Investigator Group
National Eye Institute (NEI)
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE December 11, 2009
First Posted Date  ICMJE December 15, 2009
Results First Submitted Date  ICMJE April 6, 2017
Results First Posted Date  ICMJE May 8, 2019
Last Update Posted Date May 19, 2020
Study Start Date  ICMJE January 2010
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Deterioration by 6 Months - Older Cohort [ Time Frame: 6 months ]
    The primary outcome measure for this study was whether the participant's condition had deteriorated within 6 months after randomization. Deterioration was defined as meeting one or both of the following criteria during a masked examination at either the 3-month or 6-month visit: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
  • Deterioration by 3 Years - Older Cohort [ Time Frame: 3 years ]
    The primary outcome measure for this study was whether the participant's condition had deteriorated within 3 years after randomization. Deterioration was defined as meeting one or both of the following criteria during any masked examination between 3 months and 3 years after randomization: 1) a constant exotropia (throughout the exam) of 10∆ or greater at distance and near by SPCT, confirmed by a retest, or 2) loss of near stereoacuity of 2 octaves (0.6 log arcsec) or more from the better of a test and retest of Preschool Randot stereoacuity at baseline, confirmed by a retest. In addition, participants were classified as deteriorated for the primary analysis if they started using non-randomized treatment (i.e., any treatment in the observation group; any treatment other than patching in the patching group) without first meeting one of the two protocol-specified deterioration criteria.
  • Deterioration by 6 Months - Younger Cohort [ Time Frame: 6 months ]
    The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was defined as a constant exotropia of 10 D or more at distance and near by SPCT, confirmed by a retest, at either the 3- or 6-month visit.
  • Deterioration by 3 Years - Younger Cohort [ Time Frame: 3 years ]
    The primary outcome measure was deterioration of the intermittent exotropia (IXT) within 6 months after randomization. Motor deterioration was defined as a constant exotropia of 10 D or more at distance and near by SPCT, confirmed by a retest, during any masked examination between 3 months and 3 years after randomization.
Original Primary Outcome Measures  ICMJE
 (submitted: December 11, 2009)
  • Deterioration by 6 months as assessed by motor alignment and stereoacuity at near [ Time Frame: 6 months ]
  • Deterioration by 3 years as assessed by motor alignment and stereoacuity at near [ Time Frame: 3 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2019)
  • Distance Stereoacuity - 3 Years [ Time Frame: Between baseline and 3 years ]
    Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity. A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at distance is reported at 3 years, as is the change in distance stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec. For change in stereo, positive change indicates improvement in stereo.
  • Near Stereoacuity - 6 Months [ Time Frame: 6 months ]
    Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity. A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at near is reported at 3 years, as is the change in near stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec. Outcome based on initial testing regardless of whether a retest was completed for suspected deterioration. Change is calculated as baseline level minus 6-month level. For change in stereo, positive change indicates improvement in stereo.
  • Near Stereoacuity - 3 Years [ Time Frame: between baseline and 3 years ]
    Stereoacuity scores (seconds of arc) were calculated based on the Randot Preschool stereoacuity test (scores: 800, 400, 200, 100, 60 and 40). Seconds of arc refers to the visual angle that is being measured in order to determine depth perception. Lower scores indicate better stereoacuity. A logarithm base 10 transformation was used to convert stereoacuity scores to the log scale to calculate descriptive statistics (reported as log of seconds of arc, or log arcsec). The stereoacuity at near is reported at 3 years, as is the change in near stereoacuity from baseline to 3 years. Both were reported as log of seconds of arc, or log arcsec. For change in stereo, positive change indicates improvement in stereo.
  • Exotropia Control at Distance - 6 Months [ Time Frame: 6 months ]
    Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change. Numeric values for exotropia control were assigned so that the following categories were created: Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
    1. No exotropia unless dissociated, recovers 1-5 secs
    2. No exotropia unless dissociated, recovers >5 secs
    3. Exotropia <50% of 30-second observation
    4. Exotropia >50% of 30-second observation
    5. Constant exotropia
    Lower scores indicate better control.
  • Exotropia Control at Distance - 3 Years [ Time Frame: 3 years ]
    Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change. Numeric values for exotropia control were assigned so that the following categories were created: Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
    1. No exotropia unless dissociated, recovers 1-5 secs
    2. No exotropia unless dissociated, recovers >5 secs
    3. Exotropia <50% of 30-second observation
    4. Exotropia >50% of 30-second observation
    5. Constant exotropia
    Lower scores indicate better control.
  • Exotropia Control at Near - 6 Months [ Time Frame: 6 months ]
    Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change. Numeric values for exotropia control were assigned so that the following categories were created: Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
    1. No exotropia unless dissociated, recovers 1-5 secs
    2. No exotropia unless dissociated, recovers >5 secs
    3. Exotropia <50% of 30-second observation
    4. Exotropia >50% of 30-second observation
    5. Constant exotropia
    Lower scores indicate better control.
  • Exotropia Control at Near - 3 Years [ Time Frame: 3 years ]
    Change in control is calculated as baseline level minus 3-year level, so positive change = improvement. Scale Range: 0 to 5. Improvement in control was defined as an improvement of 3 points based on the 3-point threshold for real change. Numeric values for exotropia control were assigned so that the following categories were created: Not applicable (no exodeviation) 0: No exotropia unless dissociated, recovers <1 secs (phoria)
    1. No exotropia unless dissociated, recovers 1-5 secs
    2. No exotropia unless dissociated, recovers >5 secs
    3. Exotropia <50% of 30-second observation
    4. Exotropia >50% of 30-second observation
    5. Constant exotropia
    Lower scores indicate better control.
  • PACT Exodeviation at Distance - 6 Months [ Time Frame: 6 months ]
    The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time). log arcsec = logarithm of seconds of arc; Δ = prism diopter
  • PACT at Distance - 3 Years [ Time Frame: 3 years ]
    The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time). Improvement in PACT at distance was defined as a decrease of ≥8∆ because this amount exceed the repeatability coefficient of 7.2∆ for PACT angles larger than 20∆ at distance. log arcsec = logarithm of seconds of arc; Δ = prism diopter
  • PACT at Near - 6 Months [ Time Frame: 6 months ]
    The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time). log arcsec = logarithm of seconds of arc; Δ = prism diopter
  • PACT at Near - 3 Years [ Time Frame: 3 years ]
    The prism and alternate cover test (PACT) is used to measure the angle of strabismus, or deviation, in prism diopters. This is measured separately at distance and at near. Smaller numbers are better because they indicate a smaller angle of deviation. For change in PACT, positive change indicates improvement (i.e. decrease in angle over time). Improvement in PACT at near was defined as a decrease of ≥13∆ because this amount exceed the repeatability coefficient of 12.8∆ for PACT angles larger than 20∆ at near. log arcsec = logarithm of seconds of arc; Δ = prism diopter
Original Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2009)
  • distance stereoacuity [ Time Frame: every 6 months for 3 years of follow-up ]
  • monofixation status [ Time Frame: every 6 months for 3 years of follow-up ]
  • development of amblyopia [ Time Frame: every 6 months for 3 years of follow-up ]
  • health related quality of life [ Time Frame: every 6 months for 3 years of follow-up ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Observation Versus Occlusion Therapy for Intermittent Exotropia
Official Title  ICMJE A Randomized Clinical Trial of Observation Versus Occlusion Therapy for Intermittent Exotropia
Brief Summary

The present study is being conducted to assess the natural history of intermittent exotropia and to establish the effectiveness of occlusion in its treatment.

Study Objectives:

  • To determine the effectiveness of occlusion for the treatment of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest
  • To determine the natural history of intermittent exotropia among patients aged 3 to < 11 years who have baseline near stereoacuity of 400 arcsec or better by Preschool Randot stereotest
Detailed Description

Intermittent exotropia (IXT) is the most common form of childhood-onset exotropia with an incidence of 32.1 per 100,000 in children under 19 years of age. Intermittent exotropia is characterized by an exotropia that is not constant and is mainly present in the distance but may also be present at near. Many cases of IXT are treated using non-surgical interventions, such as part-time occlusion, fusional vergence exercises, and over-minus lenses. The rationale for such interventions is that they may improve the ability to control the IXT and preserve stereoacuity, thereby potentially addressing both visual function and social concerns, and may delay or eliminate the need for surgical correction of IXT. Nevertheless, the natural history of IXT is unknown and in many cases it is not known whether withholding treatment may in fact allow for spontaneous resolution or improvement in IXT, making non-surgical or surgical intervention unnecessary. Moreover, although non-surgical treatments for IXT are commonly prescribed, such treatments have not been subjected to rigorous study and their efficacy in improving visual function or social concerns remains unclear.

One aim of the present study is to better understand the natural history of IXT. Available reports on the natural history of IXT disagree on the progression of the disease. A 1966 study by von Noorden (cited in von Noorden and Campos) found that over an average of 3.5 years of follow-up, 75% of 51 patients showed signs of IXT progression, 9% showed no change, and 16% improved without therapy. A 1968 retrospective study by Hiles et al found that after a minimum of 6 years follow up with observation and nonsurgical treatment, 81% of 48 patients showed no change in angle of deviation. The results of more recent retrospective studies show some reporting that the majority of cases improve over time, others reporting that most cases remain stable, and still others reporting that most cases deteriorate. It is therefore unclear what proportion of patients, if left untreated, is likely to deteriorate, improve, or remain stable over time. Natural history data acquired during this study will help determine not only what proportion of patients change over time, but whether there are associated prognostic indicators of deterioration or improvement. Such data will not only enable better identification of those patients with IXT likely to benefit from treatment and those for whom treatment is likely to be unnecessary, but will also improve the quality of medical advice to parents regarding the likely progression of the disease, thus alleviating anxiety.

The aim of most forms of non-surgical treatments for IXT is to improve the strength and/or quality of binocular single vision by either eliminating suppression, increasing awareness of diplopia, and/or increasing positive fusional amplitudes. Commonly used non-surgical treatment methods include: occlusion, fusional vergence exercises (sometimes known as vision therapy or orthoptics), and over-minus lenses. When surveyed in 1990, members of the American Association for Pediatric Ophthalmology and Strabismus reported that occlusion was the most commonly used form of non-surgical treatment. More recently (2008), a poll of our investigator group revealed again that occlusion was the most widely prescribed non-surgical treatment for children affected by IXT.

Occlusion is thought to work by interrupting the development of or eliminating already present suppression, an adaptation to avoid diplopia in IXT. Persistent or entrenched suppression prevents normal binocular vision and may lead to permanent loss of stereoacuity. If successful, occlusion may then result in improved binocular sensory fusion.

As reported in recent reviews of treatment for IXT, previous studies of occlusion vary regarding the recommended occlusion dose (from 3 hours a day to full time), the optimum duration of occlusion treatment (from 6 weeks to 42 months), and which eye should be occluded (preferred/dominant eye or alternate eyes). For the majority of studies, part-time occlusion, rather than full-time occlusion was preferred. In the three occlusion studies conducted prospectively, the recommended dose was either 3 hours a day, 3 to 6 hours a day, or 4 to 6 hours a day, and the duration of occlusion ranged from 3 months to 6 months to up to 42 (mean 15) months. Nevertheless, these previous studies of occlusion for the treatment of IXT used a variety of outcome measures at a variety of non-standardized time points; therefore, no definite conclusions can be drawn from the existing literature.

Although occlusion treatment for IXT treatment is widely used, there have been no randomized clinical trials evaluating its effectiveness. Understanding the degree of effectiveness of occlusion treatment for IXT and the natural history of IXT has important public health implications. Successful restoration of binocular alignment and normal binocular function with occlusion therapy, or spontaneous improvement, will reduce the proportion of children undergoing surgery. Defining the rate of success with either occlusion or observation is therefore important in planning treatment for children with IXT. Alternatively, evidence of low treatment effectiveness with occlusion will help avoid unnecessary treatment.

The present study is being conducted to assess the natural history of IXT and to establish the effectiveness of occlusion in its treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Exotropia
Intervention  ICMJE Device: occlusion treatment
Patients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion.
Other Names:
  • occlusion therapy
  • patching
Study Arms  ICMJE
  • No Intervention: Observation
    Patients randomized to the observation group will receive no treatment (other than refractive correction).
  • Active Comparator: Occlusion Therapy
    Patients randomized to the occlusion treatment group will receive occlusion (patching) for 3 hours per day for at least 3 months. Choice of which eye to occlude, or whether to alternate daily, is at investigator's discretion.
    Intervention: Device: occlusion treatment
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 22, 2016)
611
Original Estimated Enrollment  ICMJE
 (submitted: December 11, 2009)
336
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 12 months to < 11 years
  • Intermittent exotropia (manifest deviation) meeting all of the following criteria:

    • Intermittent exotropia at distance OR constant exotropia at distance and either intermittent exotropia or exophoria at near
    • Exodeviation at least 15PD at distance OR near measured by prism and alternate cover test (PACT)
    • Exodeviation at least 10PD at distance measured by PACT
  • No previous surgical or non-surgical treatment for IXT (other than refractive correction)
  • Visual acuity in the worse eye at least 0.3 logMAR (20/40 on ATS HOTV or 70 letters on E-ETDRS) for children ≥ 3 years of age
  • No interocular difference of visual acuity more than 0.2 logMAR (2 lines on ATS HOTV or 10 letters on E-ETDRS) for children ≥ 3 years of age
  • No hyperopia greater than +3.50 D spherical equivalent in either eye
  • No myopia greater than -6.00 D spherical equivalent in either eye
  • No prior strabismus, intraocular, or refractive surgery
  • No abnormality of the cornea, lens, or central retina
  • Investigator willing to observe the IXT untreated for 3 years unless specific criteria for deterioration are met

Exclusion Criteria:

  • Pure phoria at both distance and near
  • Prior non-surgical treatment for IXT other than refractive correction (e.g., vergence therapy, occlusion, vision therapy/orthoptics, or deliberate over-minus with spectacles more than 0.50D)
  • Previous amblyopia treatment other than refractive correction within 1 year
  • Vision therapy/orthoptics for any reason within the last year
  • Interocular visual acuity difference more than 0.2 logMAR (2 lines on ATS HOTV for patients 3 to < 7 years old or 10 letters on E-ETDRS for patients ≥ 7 years old) (patients ≥ 3 years only) and/or investigator plans to initiate amblyopia treatment at this time.
  • Limitation of ocular rotations due to restrictive or paretic strabismus
  • Craniofacial malformations affecting the orbits
  • Ocular disorders which would reduce visual acuity (except refractive error)
  • Prior strabismus surgery or botulinum injection, intraocular surgery, or refractive surgery
  • Strabismus surgery planned
  • Known skin reactions to patch or bandage adhesives
  • Significant neurological impairment such as cerebral palsy. Patients with mild speech delays or common reading and/or learning disabilities are not excluded.
  • Investigator planning to change refractive correction at this time (if the patient is otherwise eligible, the investigator should consider prescribing refractive correction and bringing the patient back at a later time for enrollment)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Months to 10 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01032330
Other Study ID Numbers  ICMJE NEI-146
2U10EY011751 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: In accordance with the NIH data sharing policy, a de-identified database is placed in the public domain on the PEDIG public website after the completion of each protocol and publication of the primary manuscript.
Time Frame: The data from the 6-month study is entered. The data for the 3-year study will be made available in 2020.
Access Criteria: Users will need a valid email address
URL: https://public.jaeb.org/pedig/stdy/153
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE
  • Pediatric Eye Disease Investigator Group
  • National Eye Institute (NEI)
Investigators  ICMJE
Study Chair: Susan A Cotter, O.D., M.S. Southern California College of Optometry, Fullerton, CA
Study Chair: Brian G Mohney, M.D. Department of Ophthalmology, Mayo Clinic, Rochester, MN
PRS Account Jaeb Center for Health Research
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP