Clinical trial NCT00622726: Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity
Official title: Intravitreal Bevacizumab (AvastinTM) Injections Versus Conventional Laser Surgery for Vision-threatening Retinopathy of Prematurity: a Prospective, Randomized, Non-blinded, Controlled, Multi-center, Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Vascular Endothelial Growth Factor
Angiogenesis Inhibitor
Premature infants
Bevacizumab
Zone I or Posterior Zone II ROP
Aggressive Posterior ROP
Stage 3 ROP
Neonatal Intensive Care Unit
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2008-02-25
Enrollment: 150
Sex: ALL
Minimum age (years): 4
Maximum age (years): 22
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to determine the efficacy and additional advantages of intravitreal bevacizumab in the treatment of ROP for both Zone I and Zone II Posterior.

Detailed description: This phase 2 study assessed the anti-neovascularization activity of intravitreal bevacizumab, as determined by regression of neovascular vessels of retinopathy of prematurity (ROP), in neonates with acute stage 3 ROP in zone I or posterior zone II with plus disease. This study enrolled 150 confirmed cases of vision threatening ROP which have definite plus disease \[ranging from Early Treatment for Retinopathy of Prematurity, to Cryotherapy for Retinopathy of Prematurity . This was done because of the controversy regarding determining plus disease and the increasing concern that many infants are being treated whose ROP would spontaneously regress. Bevacizumab will be administered intravitreally using 0.625 mg (0.025 ml) injections into each eye. There was no intent to give additional doses unless there was a recurrence of vision threatening stage 3 ROP with plus disease since the disease is self limited by completion of vascularization. Clinical response and any evidence of ocular toxicities were documented by retinal imaging system (manufactured by Clarity Medical Systems, Inc.) taken pre-injection, one week and one month post injection, and at 6 months of age (54 weeks postmenstrual age)(window of 50 to 70 weeks PMA)(primary outcome) and at 12 months of age (80 weeks postmenstrual age)(window of 75 to 100 weeks PMA)(structural documentation). Using the same retinal imaging system, fluorescein angiograms have been taken when possible to document structural outcomes in greater detail. No evidence of systemic toxicities were documented by appropriate clinical and laboratory tests.

Eligibility criteria: Inclusion Criteria:

1. Infants who have been screened by the American Academy of Ophthalmology, the American Academy of Pediatrics, and the American Association for Pediatric Ophthalmology and Strabismus guidelines (≤1500 grams at birth and ≤30 weeks gestation) who develop Stage 3 ROP in zone I or posterior zone II.
2. Informed Consent from a parent or guardian.

Exclusion Criteria:

1. Infants who have a congenital systemic anomaly or have a congenital ocular abnormality.
2. Infants who cannot be treated by conventional laser therapy because of problems with media clarity. Generally, blind external cryotherapy would be utilized as an initial therapy and the infant would be excluded from the study even if the media clear subsequently.
3. Informed Consent from a parent or guardian refused. This will mean that an infant automatically will receive laser therapy. Bevacizumab (Avastin®) treatment cannot be given outside of the Protocol. No data will be used from an infant without Informed Consent.

Primary outcomes:
measure: Number of Eyes Showing Recurrence of Neovascularization Arising From the Retinal Vessels and Requiring Re-treatment
timeFrame: 54 weeks postmenstrual age (window of 50 to 70 weeks)
Secondary outcomes:
measure: Myopia in Zone I and Posterior Zone II of Infant Eyes
timeFrame: 2.5 years of age
measure: Visual Acuity
timeFrame: Age 7 years.
Other outcomes:
Locations:
city: Pasadena
country: United States
facility: Huntington Memorial Hospital
state: California
city: Denver
country: United States
facility: Presbyterian-St. Luke's Hospital
state: Colorado
city: Peoria
country: United States
facility: OSF St. Francis Medical Center-Children's Hospital of Illinois
state: Illinois
city: Columbia
country: United States
facility: Palmetto Health Richland Hospital
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Baptist Hospital
state: South Carolina
city: Corpus Christi
country: United States
facility: Driscoll Children's Hospital
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: El Paso
country: United States
facility: Las Palmas Medical Center
state: Texas
city: El Paso
country: United States
facility: R.E. Thomason Hospital
state: Texas
city: El Paso
country: United States
facility: Del Sol Medical Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: Houston
country: United States
facility: St. Joseph Medical Center
state: Texas
city: Houston
country: United States
facility: Children's Memorial Hermann Hospital
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Southwest Hospital
state: Texas
city: Webster
country: United States
facility: Clear Lake Regional Medical Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Helen A. Mintz-Hittner, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mintz-Hittner HA, Best LM. Antivascular endothelial growth factor for retinopathy of prematurity. Curr Opin Pediatr. 2009 Apr;21(2):182-7. doi: 10.1097/MOP.0b013e32832925f9.
citation: Mintz-Hittner HA. Avastin as monotherapy for retinopathy of prematurity. J AAPOS. 2010 Feb;14(1):2-3. doi: 10.1016/j.jaapos.2009.12.002. No abstract available.
citation: Mintz-Hittner HA. Intravitreal pegaptanib as adjunctive treatment for stage 3+ ROP shown to be effective in a prospective, randomized, controlled multicenter clinical trial. Eur J Ophthalmol. 2012 Sep-Oct;22(5):685-6. doi: 10.5301/ejo.5000176.
citation: Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev. 2012 Dec;88(12):937-41. doi: 10.1016/j.earlhumdev.2012.09.019. Epub 2012 Oct 15.
citation: Mintz-Hittner HA, Kuffel RR Jr. Intravitreal injection of bevacizumab (avastin) for treatment of stage 3 retinopathy of prematurity in zone I or posterior zone II. Retina. 2008 Jun;28(6):831-8. doi: 10.1097/IAE.0b013e318177f934.
citation: Kong L, Mintz-Hittner HA, Penland RL, Kretzer FL, Chevez-Barrios P. Intravitreous bevacizumab as anti-vascular endothelial growth factor therapy for retinopathy of prematurity: a morphologic study. Arch Ophthalmol. 2008 Aug;126(8):1161-3. doi: 10.1001/archophthalmol.2008.1. No abstract available.
citation: Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011 Feb 17;364(7):603-15. doi: 10.1056/NEJMoa1007374.
citation: Geloneck MM, Chuang AZ, Clark WL, Hunt MG, Norman AA, Packwood EA, Tawansy KA, Mintz-Hittner HA; BEAT-ROP Cooperative Group. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol. 2014 Nov;132(11):1327-33. doi: 10.1001/jamaophthalmol.2014.2772.
citation: Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical Management of Recurrent Retinopathy of Prematurity after Intravitreal Bevacizumab Monotherapy. Ophthalmology. 2016 Sep;123(9):1845-55. doi: 10.1016/j.ophtha.2016.04.028. Epub 2016 May 27.