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

October 16, 2013 updated by: Michael T. Trese, M.D., Vision Research Foundation
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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2T 5R6
        • Ells Retina Centre
  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Children's Hospital Los Angeles
      • Los Angeles, California, United States, 90095
        • Jules Stein Eye Institute, UCLA
      • Palo Alto, California, United States, 94303
        • Eye Insitute at Stanford
    • Florida
      • Miami, Florida, United States, 33136
        • Bascon Palmer Eye Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Eye Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Children's Hospital, Dept. of Ophthalmology
    • Michigan
      • Royal Oak, Michigan, United States, 48073
        • Associated Retinal Consultants/William Beaumont Hospital
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Insitute of Ophthalmology and Medical Science, New Jersey Medical School
    • New York
      • New York, New York, United States, 10021
        • Department of Ophthalmology, Weill Cornell Medical College
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Abrahamson Pediatric Eye Institute, Cincinnati Children's Hospital Medical Center
      • Cleveland, Ohio, United States, 44105
        • Cleveland Clinic
      • Dublin, Ohio, United States, 43016
        • Midwest Retina
      • Mayfield Heights, Ohio, United States, 44134
        • University Hospitals Eye Insitute, Rainbow Babies & Children's Hospital
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19134
        • St. Christopher's Hospital for Children, Drexel Univ. School of Medicine
    • Texas
      • Austin, Texas, United States, 78705
        • Austin Retina Associates
      • Houston, Texas, United States, 77030
        • Texas Children's Hospital
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • University of Utah, Moran Eye Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53266
        • Medical College of Wisconsin--Eye Insititute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 8 months (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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)
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Names:
  • Avastin
Active Comparator: 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).
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Names:
  • Avastin
Active Comparator: Laser ablation
1/3 of study participants will be randomized to this treatment in both eyes (study eye and fellow eye)
Drug: Bevacizumab
A single dosage of: 0.625mg(0.025cc)or 0.75mg(0.03cc) will be given intravitreally.
Other Names:
  • Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To demonstrate non-inferiority of Anti-VEGF treatment to standard-of-care laser
Time Frame: With patient #58, 116 and 174 (within 3 months after each patient being enrolled)
It is the intent of this clinical study to develop alternative therapy (a single bevacizumab injection) to standard therapy (laser ablation) and to show that bevacizumab is as safe and efficacious as laser.
With patient #58, 116 and 174 (within 3 months after each patient being enrolled)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Decreased laser ablation and improved vascular maturity
Time Frame: With patient #58, 116 & 174 (within 3 months after each patient being enrolled)
These 2 end-points will be monitored by evidence of persistent disease and presence/absence of progression to retinal detachment. If either or both of these objectives are not met, it is indicative of failure of treatment.
With patient #58, 116 & 174 (within 3 months after each patient being enrolled)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vision Research Foundation

Investigators

  • Principal Investigator: Michael T Trese, MD, Vision Research Foundation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2012

Primary Completion (Anticipated)

April 1, 2015

Study Completion (Anticipated)

July 1, 2018

Study Registration Dates

First Submitted

October 26, 2010

First Submitted That Met QC Criteria

October 29, 2010

First Posted (Estimate)

November 2, 2010

Study Record Updates

Last Update Posted (Estimate)

October 17, 2013

Last Update Submitted That Met QC Criteria

October 16, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 002 (University of CT Health Center)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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