Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity (BLOCK-ROP)
Primary Purpose
Retinopathy of Prematurity
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Bevacizumab
Sponsored by
About this trial
This is an interventional treatment trial for Retinopathy of Prematurity focused on measuring Pan-Vascular Endothelial Growth Factor Blockade, Safety
Eligibility Criteria
Eligibility criteria
- Premature newborn infants with bilateral progressive APROP despite complete peripheral retinal ablation.
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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)
Sites / Locations
- Childrens Hospital
- Jules Stein Eye Center
- California Vitreoretinal Center
- Bascom Palmer Eye Institute
- Emory Eye Center
- Children's Hospital / Dept. Ophthalmology
- William Beaumont Hospital
- University of North Carolina/Ophthalmology
- University of Pennsylvania/Scheie Eye Institute
- Baylor College of Medicine
- Calgary Health
Outcomes
Primary Outcome Measures
The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity.
Secondary Outcome Measures
The secondary therapeutic study aim is to determine the efficacy of treatment with Bevacizumab (Avastin) for improving structural outcome without surgical intervention.
Full Information
NCT ID
NCT00702819
First Posted
June 19, 2008
Last Updated
January 26, 2010
Sponsor
Vision Research Foundation
1. Study Identification
Unique Protocol Identification Number
NCT00702819
Brief Title
Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity
Acronym
BLOCK-ROP
Official Title
Phase 1 Trial of Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity
Study Type
Interventional
2. Study Status
Record Verification Date
June 2008
Overall Recruitment Status
Terminated
Why Stopped
Low enrollment due to the stringent enrollment criteria. Unable to answer study questions
Study Start Date
June 2008 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
July 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Vision Research Foundation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinopathy of Prematurity
Keywords
Pan-Vascular Endothelial Growth Factor Blockade, Safety
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Dosage of 0.75mg/0.03ml injectable, one time only.
Primary Outcome Measure Information:
Title
The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity.
Time Frame
Weekly
Secondary Outcome Measure Information:
Title
The secondary therapeutic study aim is to determine the efficacy of treatment with Bevacizumab (Avastin) for improving structural outcome without surgical intervention.
Time Frame
Weekly
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Weeks
Maximum Age & Unit of Time
36 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Eligibility criteria
Premature newborn infants with bilateral progressive APROP despite complete peripheral retinal ablation.
Inclusion Criteria:
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
Exclusion Criteria:
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael T Trese, MD
Organizational Affiliation
Vision Research Foundation
Official's Role
Study Chair
Facility Information:
Facility Name
Childrens Hospital
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Jules Stein Eye Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
California Vitreoretinal Center
City
Menlo Park
State/Province
California
ZIP/Postal Code
94025
Country
United States
Facility Name
Bascom Palmer Eye Institute
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory Eye Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Children's Hospital / Dept. Ophthalmology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
William Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Name
University of North Carolina/Ophthalmology
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7040
Country
United States
Facility Name
University of Pennsylvania/Scheie Eye Institute
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Calgary Health
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2S-=2H4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
16770257
Citation
Bakri SJ, Snyder MR, Pulido JS, McCannel CA, Weiss WT, Singh RJ. Six-month stability of bevacizumab (Avastin) binding to vascular endothelial growth factor after withdrawal into a syringe and refrigeration or freezing. Retina. 2006 May-Jun;26(5):519-22. doi: 10.1097/01.iae.0000225354.92444.7a.
Results Reference
background
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Pan-VEGF Blockade for the Treatment of Retinopathy of Prematurity
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