Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)

NCT ID: NCT01232777

Last Updated: 2013-10-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2012-06-30

Study Completion Date

2018-07-31

Brief Summary

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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

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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.

Conditions

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Retinopathy of Prematurity

Keywords

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Retinopathy of Prematurity Bevacizumab Avastin Vascular Endothelial Growth Factor

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Bevacizumab (Avastin) 0.75mg/0.03cc

1/3 of study participants will be randomized to this treatment in one eye (study eye) and the other eye will receive laser (fellow eye)

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.

Bevacizumab (Avastin) 0.625mg/0.025cc

1/3 of patients will be randomized to this treatment in 1 eye (study eye) and the other eye will receive laser (fellow eye).

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.

Laser ablation

1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye)

Group Type ACTIVE_COMPARATOR

Bevacizumab

Intervention Type DRUG

A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.

Interventions

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Bevacizumab

A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.

Intervention Type DRUG

Other Intervention Names

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Avastin

Eligibility Criteria

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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)
Minimum Eligible Age

30 Weeks

Maximum Eligible Age

36 Weeks

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vision Research Foundation

OTHER

Sponsor Role lead

Responsible Party

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Michael T. Trese, M.D.

VitreoRetinal Surgeon & Researcher

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michael T Trese, MD

Role: PRINCIPAL_INVESTIGATOR

Vision Research Foundation

Locations

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Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

Jules Stein Eye Institute, UCLA

Los Angeles, California, United States

Site Status

Eye Insitute at Stanford

Palo Alto, California, United States

Site Status

Bascon Palmer Eye Institute

Miami, Florida, United States

Site Status

Emory Eye Center

Atlanta, Georgia, United States

Site Status

Children's Hospital, Dept. of Ophthalmology

Boston, Massachusetts, United States

Site Status

Associated Retinal Consultants/William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

Insitute of Ophthalmology and Medical Science, New Jersey Medical School

Newark, New Jersey, United States

Site Status

Department of Ophthalmology, Weill Cornell Medical College

New York, New York, United States

Site Status

Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Midwest Retina

Dublin, Ohio, United States

Site Status

University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital

Mayfield Heights, Ohio, United States

Site Status

St. Christopher's Hospital for Children, Drexel Univ. School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Austin Retina Associates

Austin, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

University of Utah, Moran Eye Center

Salt Lake City, Utah, United States

Site Status

Medical College of Wisconsin--Eye Insititute

Milwaukee, Wisconsin, United States

Site Status

Ells Retina Centre

Calgary, Alberta, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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002

Identifier Type: -

Identifier Source: org_study_id