Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity
Stopped early · Phase 1
Conditions studied: Retinopathy of Prematurity
In brief
Retinopathy of Prematurity (ROP) is a leading cause of blindness in children in developed countries around the world, and an increasing cause of blindness in developing countries. The retina lines the inside of the eye. It functions as "film" within the camera which is the eye. When an infant is born prematurely, the vascular network necessary to nourish the retina has not fully developed. As a consequence, in some infants abnormal vessels proliferate instead of the normal ones - a condition known as ROP. The abnormal vessels carry scar tissue along with them, and may lead to retinal detachment and blindness if the eye is not treated. The Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study demonstrated that ablation of the peripheral avascular retina reduced the risk of poor structural and visual outcome due to retinal distortion or detachment in ROP (1980's). The ablated retina is not functional and is not amenable to regeneration. Peripheral retinal ablation is not universally effective in fostering regression of ROP. This is particularly true for an aggressive form of ROP (aggressive posterior ROP, or APROP) which typically afflicts profoundly premature and infirm neonates. In this subset of infants, progression of ROP to bilateral retinal detachment and blindness occurs despite timely and complete peripheral retinal laser ablation. Rationale The development of ROP is largely dependent on vascular endothelial growth factor (VEGF). When an infant is born prematurely the relatively hyperoxic environment the baby is introduced to shuts down the production of VEGF. Retinal maturation is delayed. Subsequently, at a time when intraocular VEGF levels would normally be declining late in the third trimester of pregnancy, abnormally high levels of VEGF are seen due to large areas of avascular retina and associated tissue hypoxia. The availability of FDA-approved drugs for anti-VEGF treatment renders it possible to treat such eyes off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such as ranibizumab (Lucentis) and bevacizumab (Avastin), which cause complete blockage of VEGF-A. As VEGF is required in the developing retina for normal angiogenesis, and our goal is not to penetrate tissue, but to block the excessive levels of VEGF trapped within the overlying vitreous which is responsible for the abnormal vasculature in ROP. For purposes of this study the investigators have chosen bevacizumab (Avastin), which will: a) attain complete blockage (vs. Macugen) of intravitreal VEGF-A, and; b) which is limited in its ability to penetrate tissues because it is a full antibody (vs. Lucentis, an antibody fragment specifically designed for better tissue penetration), and is more likely to restore VEGF homeostasis within the developing retina.
Key facts
- Study ID
- NCT00702819
- Run by
- Vision Research Foundation
- People needed
- 2
- Starts
- 2008-06-01
- Expected to finish
- 2009-07-01
- Last updated by the study team
- 2010-01-27
Who can join
Age: 1 and older, up to 1. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- Inborn babies at participating NICUs (must meet inclusion criteria 3 through 7)
- Outborn babies transferred to participating NICU (must meet inclusion criteria 3 through 7)
- Aggressive posterior ROP
- Adequate/appropriate laser ablation
- Failed standard laser treatment (persistent Plus or recurrent Plus at a minimum of 1 week post-laser)
- Post-menstrual age less than 36 weeks
- Post-menstrual age greater than 30 weeks
You may not qualify if…
- Fatal systemic anomaly
- An ocular anomaly of one or both eyes affecting the retina or choroid
- An ocular anomaly precluding use of the RetCam (eg: microphthalmia)
- Neonatologist feels inclusion will unduly challenge the infant
- Refusal of initial consent
- Refusal of subsequent evaluation
- Media opacity precluding fundus visualization (eg: cataract)
- Any ocular or periocular infection(s)
Where it is running
- Childrens Hospital — Los Angeles, California, United States
- Jules Stein Eye Center — Los Angeles, California, United States
- California Vitreoretinal Center — Menlo Park, California, United States
- Bascom Palmer Eye Institute — Miami, Florida, United States
- Emory Eye Center — Atlanta, Georgia, United States
- Children's Hospital / Dept. Ophthalmology — Boston, Massachusetts, United States
- William Beaumont Hospital — Royal Oak, Michigan, United States
- University of North Carolina/Ophthalmology — Chapel Hill, North Carolina, United States
- University of Pennsylvania/Scheie Eye Institute — Philadelphia, Pennsylvania, United States
- Baylor College of Medicine — Houston, Texas, United States
- Calgary Health — Calgary, Alberta, Canada
Full record on ClinicalTrials.gov
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