Clinical trial NCT00027222: The Early Treatment for Retinopathy of Prematurity Study (ETROP)
Official title: The Early Treatment for Retinopathy of Prematurity Study (ETROP)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Retinopathy of Prematurity
Lead sponsor: National Eye Institute (NEI)
Sponsor class: NIH
First posted: 2001-10-29
Sex: ALL
Minimum age (years): 0
Maximum age (years): 42
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The goal of the Early Treatment for Retinopathy of Prematurity Study (ETROP) is to test the hypothesis that earlier treatment in carefully selected cases will result in an overall better visual outcome than treatment at the conventional CRYO-ROP threshold point in the disease.

Detailed description: At age 5 1/2 years, the oldest age for which follow-up data are available, children with threshold ROP who were enrolled in the Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) -- Outcome Study showed fewer treated eyes (31.5 percent) than control eyes (48 percent) that were blind (P\<0.001). Of those eyes that had a favorable structural outcome, with or without retinal ablation (cryotherapy to destroy the fringe of the retina through freezing), only a small percentage had best corrected visual acuity better than or equal to 20/40 at age 5 1/2 years (13 percent in the treated group; 17 percent in the untreated control group (P=0.19)). Among the 1398 followed from the 5 large natural history centers of the CRYO-ROP follow-up study, children with retinal residua of ROP (structural changes) had measurable visual acuity that was severly affected and tended to worsen with age. The CRYO-ROP Study proved conclusively that peripheral retinal ablation improves the chances of avoiding blindness, but at least 80 percent of eyes are left with acuity less than 20/40.

Two concerns emerged from the CRYO-ROP extensive study on the natural history of ROP and treatment of threshold ROP. The first of these is failure of peripheral retinal ablation to eliminate all, or nearly all cases, of retinal detachment due to ROP. In the CRYO-ROP Study, 26 percent of eyes with threshold disease in zone II and 78 percent of eyes with zone I threshold disease had an unfavorable structural outcome despite treatment. The second concern is that most children who developed threshold ROP disease had visual acuity worse than 20/40 even if the eye had a favorable structural outcome.

Since no other treatment has yet been shown to be effective in preventing blindness from ROP, retinal ablation remains the treatment of choice. The ETROP Study will test whether earlier treatment is more effective than treatment at threshold in improving functional (visual acuity) outcome following ROP, as well as determining whether earlier treatment decreases the probability of an unfavorable structural outcome.

Earlier treatment is defined as retinal ablation administered to the avascular retina when an eye reaches high risk prethreshold retinopathy of prematurity (ROP). Prethreshold indicates any Zone I ROP; or Zone II stage 2 with plus disease, or stage 3; or Zone II with less than 5 contiguous or 8 cumulative clock hours of stage 3 ROP with plus disease. Recognizing that a substantial number of eyes undergo spontaneous resolution of ROP, eyes will be randomized to early treatment only when high risk for an unfavorable visual acuity outcome is identified. High risk will be determined using a risk model analysis program based on longitudinal natural history data obtained from the CRYO-ROP study. This model integrates risk factors to assign a risk of progression to blindness without treatment. These factors include birth weight, gestational age, ethnicity, singleton/multiple status, outborn status, Zone on first exam, severity of ROP and rate of progression of ROP. When an infant develops prethreshold ROP and greater than or equal to 15 percent risk of unfavorable outcome, randomization to early treatment of one eye will occur. Visual acuity outcome will be measured by masked observers after wearing best correction using the Teller Acuity Card Procedure at 9 months corrected age.

Eligibility criteria: Infants \<1251 grams birthweight born at participating centers and/or examined by 42 days of life are eligible. The early treatment trial requires that an infant have prethreshold retinopathy of prematurity (ROP).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: San Francisco
country: United States
facility: Smith-Kettlewell Eye Research Institute
state: California
city: Chicago
country: United States
facility: UIC Eye Center Department of Ophthalmology and Visual Sciences The Lions of Illinois Eye Research Institute
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Department of Pediatrics
state: Indiana
city: Louisville
country: United States
facility: University of Louisville Health Sciences Center
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: The Zanvyl Krieger Children's Eye Center
state: Maryland
city: Boston
country: United States
facility: Tufts University School of Medicine Department of Pediatrics
state: Massachusetts
city: Dearborn
country: United States
facility: Pediatric Ophthalmology Associates, PC
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: Cardinal Glennon Children's Hospital Neonatology Office
state: Missouri
city: Buffalo
country: United States
facility: The Children's Hospital of Buffalo Department of Ophthalmology
state: New York
city: New York
country: United States
facility: Edward S. Harkness Eye Institute
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Shirley
country: United States
facility: Eastern Long Island Retina Associate
state: New York
city: Durham
country: United States
facility: Duke University Eye Center
state: North Carolina
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: The Dean A. McGee Eye Institute
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Sciences University Casey Eye Institute
state: Oregon
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia Division of Pediatric Ophthalmology
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Women's Hospital
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine Feigin Center
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: John Moran Eye Center University of Utah Health Sciences Center
state: Utah
Study officials:
affiliation: Smith-Kettlewell Eye Research Institute
name: William V. Good, M.D.
role: STUDY_CHAIR
References:
citation: Wallace DK, Bremer DL, Good WV, Fellows R, Summers CG, Tung B, Hardy RJ. Correlation of recognition visual acuity with posterior retinal structure in advanced retinopathy of prematurity. Arch Ophthalmol. 2012 Dec;130(12):1512-6. doi: 10.1001/archophthalmol.2012.2118.
citation: Good WV, Hardy RJ, Wallace DK, Bremer D, Rogers DL, Siatkowski RM, De Becker I, Summers CG, Fellows R, Tung B, Palmer EA. beta-Blocking and racial variation in the severity of retinopathy of prematurity. Arch Ophthalmol. 2012 Jan;130(1):117-8. doi: 10.1001/archopht.130.1.117. No abstract available.
citation: VanderVeen DK, Bremer DL, Fellows RR, Hardy RJ, Neely DE, Palmer EA, Rogers DL, Tung B, Good WV; Early Treatment for Retinopathy of Prematurity Cooperative Group. Prevalence and course of strabismus through age 6 years in participants of the Early Treatment for Retinopathy of Prematurity randomized trial. J AAPOS. 2011 Dec;15(6):536-40. doi: 10.1016/j.jaapos.2011.07.017.
citation: Early Treatment for Retinopathy of Prematurity Cooperative Group; Dobson V, Quinn GE, Summers CG, Hardy RJ, Tung B, Good WV. Grating visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2011 Jul;129(7):840-6. doi: 10.1001/archophthalmol.2011.143.
citation: Quinn GE, Dobson V, Hardy RJ, Tung B, Palmer EA, Good WV; Early Treatment for Retinopathy of Prematurity Cooperative Group. Visual field extent at 6 years of age in children who had high-risk prethreshold retinopathy of prematurity. Arch Ophthalmol. 2011 Feb;129(2):127-32. doi: 10.1001/archophthalmol.2010.360.
citation: Christiansen SP, Dobson V, Quinn GE, Good WV, Tung B, Hardy RJ, Baker JD, Hoffman RO, Reynolds JD, Rychwalski PJ, Shapiro MJ; Early Treatment for Retinopathy of Prematurity Cooperative Group. Progression of type 2 to type 1 retinopathy of prematurity in the Early Treatment for Retinopathy of Prematurity Study. Arch Ophthalmol. 2010 Apr;128(4):461-5. doi: 10.1001/archophthalmol.2010.34.
citation: Early Treatment for Retinopathy of Prematurity Cooperative Group; Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Tung B, Redford M. Final visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2010 Jun;128(6):663-71. doi: 10.1001/archophthalmol.2010.72. Epub 2010 Apr 12.