NCT00702819

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.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2008

Geographic Reach
2 countries

11 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2008

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

June 19, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 20, 2008

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2009

Completed
Last Updated

January 27, 2010

Status Verified

June 1, 2008

Enrollment Period

1 year

First QC Date

June 19, 2008

Last Update Submit

January 26, 2010

Conditions

Keywords

Pan-Vascular Endothelial Growth Factor BlockadeSafety

Outcome Measures

Primary Outcomes (1)

  • The primary aim is to evaluate the safety of Bevacizumab (Avastin) administered in a single dose into the vitreous cavity.

    Weekly

Secondary Outcomes (1)

  • The secondary therapeutic study aim is to determine the efficacy of treatment with Bevacizumab (Avastin) for improving structural outcome without surgical intervention.

    Weekly

Interventions

Dosage of 0.75mg/0.03ml injectable, one time only.

Also known as: Avastin

Eligibility Criteria

Age30 Weeks - 36 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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)
  • Refusal of initial consent
  • Refusal of subsequent evaluation
  • Media opacity precluding fundus visualization (eg: cataract)
  • Any ocular or periocular infection(s)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Childrens Hospital

Los Angeles, California, 90027, United States

Location

Jules Stein Eye Center

Los Angeles, California, 90095, United States

Location

California Vitreoretinal Center

Menlo Park, California, 94025, United States

Location

Bascom Palmer Eye Institute

Miami, Florida, 33136, United States

Location

Emory Eye Center

Atlanta, Georgia, 30322, United States

Location

Children's Hospital / Dept. Ophthalmology

Boston, Massachusetts, 02115, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

University of North Carolina/Ophthalmology

Chapel Hill, North Carolina, 27599-7040, United States

Location

University of Pennsylvania/Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Calgary Health

Calgary, Alberta, T2S-=2H4, Canada

Location

Related Publications (1)

  • 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.

    PMID: 16770257BACKGROUND

MeSH Terms

Conditions

Retinopathy of Prematurity

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Retinal DiseasesEye DiseasesInfant, Premature, DiseasesInfant, Newborn, DiseasesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Michael T Trese, MD

    Vision Research Foundation

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 19, 2008

First Posted

June 20, 2008

Study Start

June 1, 2008

Primary Completion

June 1, 2009

Study Completion

July 1, 2009

Last Updated

January 27, 2010

Record last verified: 2008-06

Locations