Clinical trial NCT01232777: Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)
Official title: Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Retinopathy of Prematurity
Keywords: Retinopathy of Prematurity
Bevacizumab
Avastin
Vascular Endothelial Growth Factor
Lead sponsor: Vision Research Foundation
Sponsor class: OTHER
First posted: 2010-11-02
Enrollment: 0
Sex: ALL
Minimum age (years): 30
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether a single intravitreal (into the gel of the eye) injection of Avastin 0.625mg or 0.75mg is equivalent (non-inferior) to treatment with standard of care laser in infants with Type I pre-threshold retinopathy of prematurity (ROP) diagnosed at 30-36 weeks gestational age.

Detailed description: 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 grow 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 multi-center 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 amendable 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 sick neonates. In this subset of infants, progression of ROP to retinal detachments in both eyes and even blindness may occur despite timely and complete peripheral retinal laser ablation.

RATIONALE:

The development of ROP is largely dependant on vascular endothelial growth factor (VEGF). When an infant is born prematurely, the relatively hyperoxic environment that the baby is introduced to shuts down the production of VEGF. Retinal maturation is thus delayed. Subsequently, at a time when intraocular VEGF levels would 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 eye off-label. Available drugs include pegaptanib sodium (Macugen) for partial blockage of VEGF-A, or drugs such a 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, we 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.

Eligibility criteria: Inclusion Criteria:

* Inborn babies at participating NICU's who meet inclusion criteria
* Outborn babies transferred to participating NICU's who meet inclusion criteria
* Type 1 pre-threshold ROP
* No prior treatment
* Post menstrual age less than 36 1/7 weeks
* Post menstrual age greater than 30 weeks

Exclusion Criteria:

* Fatal systemic anomaly
* An ocular anomaly of one or both eye affecting the retina or choroid
* An ocular anomaly precluding use of the RetCam (ex., microphthalmia)
* Neonatologist feels inclusion will unduly challenge the infant
* Refusal of initial consent
* Refusal of subsequent evaluation
* Media opacity precluding fundus visualization (ex., cataract)
* Any ocular or periocular infection(s)

Primary outcomes:
measure: To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser
timeFrame: With patient #58, 116 and 174 (within 3 months after each patient being enrolled)
Secondary outcomes:
measure: Decreased laser ablation and improved vascular maturity
timeFrame: With patient #58, 116 & 174 (within 3 months after each patient being enrolled)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute, UCLA
state: California
city: Palo Alto
country: United States
facility: Eye Insitute at Stanford
state: California
city: Miami
country: United States
facility: Bascon Palmer Eye Institute
state: Florida
city: Atlanta
country: United States
facility: Emory Eye Center
state: Georgia
city: Boston
country: United States
facility: Children's Hospital, Dept. of Ophthalmology
state: Massachusetts
city: Royal Oak
country: United States
facility: Associated Retinal Consultants/William Beaumont Hospital
state: Michigan
city: Newark
country: United States
facility: Insitute of Ophthalmology and Medical Science, New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Department of Ophthalmology, Weill Cornell Medical College
state: New York
city: Cincinnati
country: United States
facility: Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dublin
country: United States
facility: Midwest Retina
state: Ohio
city: Mayfield Heights
country: United States
facility: University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: St. Christopher's Hospital for Children, Drexel Univ. School of Medicine
state: Pennsylvania
city: Austin
country: United States
facility: Austin Retina Associates
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah, Moran Eye Center
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin--Eye Insititute
state: Wisconsin
city: Calgary
country: Canada
facility: Ells Retina Centre
state: Alberta
Study officials:
affiliation: Vision Research Foundation
name: Michael T Trese, MD
role: PRINCIPAL_INVESTIGATOR
References: