Clinical trial NCT04378790: A Randomized Trial to Evaluate Sequential vs Simultaneous Patching
Official title: A Randomized Trial to Evaluate Sequential vs Simultaneous Spectacles Plus Patching for Amblyopia in Children 3 to <13 Years Old
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Amblyopia
Keywords: patching
glasses
spectacles
simultaneous
sequential
Lead sponsor: Jaeb Center for Health Research
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
name: Pediatric Eye Disease Investigator Group
First posted: 2020-05-07
Enrollment: 544
Sex: ALL
Minimum age (years): 3
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A randomized trial to determine whether simultaneous treatment with spectacles and patching has an equivalent VA outcome compared with sequential treatment, first with spectacles alone followed by patching (if needed), for previously untreated amblyopia in children 3 to \<13 years of age.

Detailed description: At an enrollment visit, distance VA will be measured in trial frames with or without cycloplegia based on a cycloplegic refraction performed within 30 days. If still apparently eligible, children will be prescribed spectacles and will then return for a spectacle baseline visit, where they will wear their new spectacles for the first time for at least 10 minutes (but no more than 24 hours) and will be tested in those new spectacles to confirm final eligibility prior to randomization.

Participants not found to be eligible in their new spectacles will end study participation. Participants eligible for the study will be randomly allocated to one of two treatment groups: Sequential (spectacles alone) and then patching if needed (monitored by ODM), or Simultaneous (spectacles and patching monitored by ODM).

After randomization, follow-up visits will occur at 8-week intervals through 56 weeks. At each visit on or after the 8-week visit, participants will be classified as either: stable/worsening or improving; those stable/worsening are then classified as having either resolved or residual amblyopia, provided that the current and most recent previous visit were completed at least 6-weeks apart (target 8 weeks) and provided the required test and retest VA testing was completed. Participants who are stable/worsening and have residual amblyopia in the sequential group will start patching (monitored by ODM) and continue to be followed every 8 weeks. Participants in the simultaneous group, or in the sequential group after having advanced to patching, who are stable/worsening but have residual amblyopia will be released to treatment at investigator discretion.

All participants continue 8-weekly visits until 56 weeks when Study participation ends.

Eligibility criteria: Inclusion Criteria:

1. Age 3 to \<13 years at the time of randomization
2. Amblyopia associated with anisometropia, strabismus, or both

   o Criteria for strabismic amblyopia: At least one of the following must be met:
   * Presence of a heterotropia on examination at distance or near fixation (with or without optical correction)
   * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia)

     * Criteria for anisometropia: At least one of the following criteria must be met:

       * 1.00 D difference between eyes in spherical equivalent (SE)
       * 1.50 D difference in astigmatism between corresponding meridians in the two eyes
     * Criteria for combined-mechanism amblyopia: Both of the following criteria must be met:
   * Criteria for strabismus are met (see above)

     * 1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
3. No previous treatment for amblyopia, including no more than 24 hours of spectacle wear.
4. Investigator planning to initiate spectacle correction of refractive error meeting the following criteria based on a cycloplegic refraction that has been performed within 30 days:

   1. Full correction of anisometropia
   2. Full correction of astigmatism with the same axis found by the cycloplegic refraction
   3. Full correction of any myopia
   4. Hyperopia must not be under corrected by more than 1.50 D, and reduction in plus sphere must be symmetric in the two eyes.
5. At enrollment, single VA measured in each eye assessed in trial frames with the spectacle correction the investigator plans to prescribe, using the investigator's routine method as follows:

   * VA in the amblyopic eye 20/40 to 20/200 inclusive.
   * Age-normal VA in the fellow eye:40,41

     * 3 years: 0.4 logMAR (20/50) or better
     * 4 years: 0.3 logMAR (20/40) or better
     * 5-6 years: 0.2 logMAR (20/32) or better
     * 7-12 years: 0.12 logMAR (78 letters) or better
   * Interocular difference ≥ 3 logMAR lines (0.3 logMAR) or ≥ 15 letters o When participants return for the Spectacle Baseline / Randomization Visit with their new spectacles, they will need to meet the same criteria as above using the ATS-HOTV or E-ETDRS protocol after wearing the new spectacles for at least 10 minutes (based upon the mean of a test and retest of VA in those new spectacles).
6. Investigator is willing to prescribe spectacle wear followed sequentially by patching or simultaneous spectacles and patching treatment per protocol.
7. Parent understands the protocol and is willing to accept randomization.
8. Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.
9. Relocation outside of area of an active PEDIG site for this study within the next 56 weeks is not anticipated.

Exclusion Criteria:

1. Myopia greater than -6.00 D spherical equivalent in either eye.
2. Previous intraocular or refractive surgery.
3. Planned strabismus surgery in the next 56 weeks.
4. Any previous treatment for amblyopia (patching, atropine, Bangerter filter, vision therapy, or binocular treatment).
5. Previous spectacle or contact lens wear for more than 24 hours.
6. Parent and participant willing to forego option of contact lens wear for the duration of the study.
7. Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above VA criteria are met).
8. Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities or attention deficit hyperactivity disorder (ADHD) are not excluded.
9. Known allergy to adhesive patches.
10. Known allergy to silicone.

Primary outcomes:
measure: Mean Change in Amblyopic Eye logMAR distance Visual Acuity
timeFrame: 56 weeks
Secondary outcomes:
measure: Pediatric Eye Questionnaire (PedEyeQ)
timeFrame: 56 weeks
measure: Proportion Achieving Stable Resolved Outcome with Spectacles Alone
timeFrame: 56 Weeks
measure: Proportion of participants who achieve Binary distance visual acuity outcomes
timeFrame: 56 weeks
measure: Time to Stable Resolved Amblyopia
timeFrame: 56 weeks
measure: Difference in Mean Change of Distance Visual Acuity after 8 Weeks on Randomized Treatment
timeFrame: 56 Weeks
measure: Change in binocularity levels
timeFrame: 56 Weeks
measure: Difference in mean change in amblyopic-eye log contrast sensitivity
timeFrame: 56 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Pediatric Eye Care; Birmingham Health Care
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Glendale
country: United States
facility: Midwestern University Eye Institute
state: Arizona
city: Phoenix
country: United States
facility: Arizonia Pediatric Eye Specialists
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Berkeley
country: United States
facility: Univ. of California- Berkeley
state: California
city: Fullerton
country: United States
facility: Marshall B. Ketchum University
state: California
city: Irvine
country: United States
facility: Univ of California, Irvine- Gavin Herbert Eye Institute
state: California
city: Loma Linda
country: United States
facility: Loma Linda University Health Care, Dept. of Ophthalmology
state: California
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles (CHLA)
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Pomona
country: United States
facility: Western University College of Optometry
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Department of Ophthalmology
state: California
city: Milford
country: United States
facility: Eye Physicians & Surgeons, PC
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Nova Southeastern University College of Optometry, The Eye Institute
state: Florida
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Tampa
country: United States
facility: University of South Florida (USF) Eye
state: Florida
city: Boise
country: United States
facility: St Luke's Hospital
state: Idaho
city: Chicago Ridge
country: United States
facility: Ticho Eye Associates
state: Illinois
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Downers Grove
country: United States
facility: Midwestern U Chicago College of Optometry
state: Illinois
city: Lisle
country: United States
facility: Progressive Eye Care
state: Illinois
city: Bloomington
country: United States
facility: Indiana School of Optometry
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University School of Optometry
state: Indiana
city: West Des Moines
country: United States
facility: Wolfe Eye Clinic
state: Iowa
city: Baltimore
country: United States
facility: Wilmer Eye Institute
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital Waltham
state: Massachusetts
city: Grand Rapids
country: United States
facility: Corewell Health
state: Michigan
city: Grand Rapids
country: United States
facility: Pediatric Ophthalmology, P.C.
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Sartell
country: United States
facility: PineCone Vision Center
state: Minnesota
city: Kansas City
country: United States
facility: Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital Eye Center
state: Missouri
city: Saint Louis
country: United States
facility: U of MO St. Louis College of Optometry
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Buffalo
country: United States
facility: Ross Eye Institute, University of Buffalo, Med School Dept Ophthalmology
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: State University of New York, College of Optometry
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Akron
country: United States
facility: Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University College of Optometry
state: Ohio
city: Oklahoma City
country: United States
facility: Dean A. McGee Eye Institute
state: Oklahoma
city: Albany
country: United States
facility: River View Family Eyecare
state: Oregon
city: Portland
country: United States
facility: Casey Eye Institute
state: Oregon
city: Erie
country: United States
facility: Pediatric Ophthalmology of Erie
state: Pennsylvania
city: Lancaster
country: United States
facility: Conestoga Eye
state: Pennsylvania
city: Philadelphia
country: United States
facility: Wills Eye Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Salus University/Pennsylvania College of Optometry
state: Pennsylvania
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Memphis
country: United States
facility: Southern College of Optometry
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center - Vanderbilt Eye Institute
state: Tennessee
city: Fort Worth
country: United States
facility: Pediatric Eye Specialists, LLP
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Science Center
state: Texas
city: San Antonio
country: United States
facility: University of the Incarnate Word
state: Texas
city: San Antonio
country: United States
facility: San Antonio Eye Center
state: Texas
city: San Antonio
country: United States
facility: University of Incarnate Word Rosenberg School of Optometry
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain Eye Care Associates
state: Utah
city: Norfolk
country: United States
facility: Virginia Pediatric Eye Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital, University of Washington
state: Washington
city: Spokane
country: United States
facility: Spokane Eye Clinical Research
state: Washington
city: Laramie
country: United States
facility: Snowy Range Vision Center
state: Wyoming
Study officials:
affiliation: Seattle Children's Hospital, University of Washington
name: Vivian Manh
role: STUDY_CHAIR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Michael Gray
role: STUDY_CHAIR
References: