Bevacizumab Eliminates the Angiogenic Threat for Retinopathy of Prematurity

Study Overview
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Brief Summary
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The purpose of this study was to determine the efficacy and additional advantages of intravitreal bevacizumab in the treatment of ROP for both Zone I and Zone II Posterior.

Detailed Description
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This phase 2 study assessed the anti-neovascularization activity of intravitreal bevacizumab, as determined by regression of neovascular vessels of retinopathy of prematurity (ROP), in neonates with acute stage 3 ROP in zone I or posterior zone II with plus disease. This study enrolled 150 confirmed cases of vision threatening ROP which have definite plus disease [ranging from Early Treatment for Retinopathy of Prematurity, to Cryotherapy for Retinopathy of Prematurity . This was done because of the controversy regarding determining plus disease and the increasing concern that many infants are being treated whose ROP would spontaneously regress. Bevacizumab will be administered intravitreally using 0.625 mg (0.025 ml) injections into each eye. There was no intent to give additional doses unless there was a recurrence of vision threatening stage 3 ROP with plus disease since the disease is self limited by completion of vascularization. Clinical response and any evidence of ocular toxicities were documented by retinal imaging system (manufactured by Clarity Medical Systems, Inc.) taken pre-injection, one week and one month post injection, and at 6 months of age (54 weeks postmenstrual age)(window of 50 to 70 weeks PMA)(primary outcome) and at 12 months of age (80 weeks postmenstrual age)(window of 75 to 100 weeks PMA)(structural documentation). Using the same retinal imaging system, fluorescein angiograms have been taken when possible to document structural outcomes in greater detail. No evidence of systemic toxicities were documented by appropriate clinical and laboratory tests.

Official Title
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Intravitreal Bevacizumab (AvastinTM) Injections Versus Conventional Laser Surgery for Vision-threatening Retinopathy of Prematurity: a Prospective, Randomized, Non-blinded, Controlled, Multi-center, Clinical Trial

Conditions
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Retinopathy of Prematurity

Intervention / Treatment
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* Drug: Bevacizumab
* Procedure: Conventional Laser for ROP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants who have been screened by the American Academy of Ophthalmology, the American Academy of Pediatrics, and the American Association for Pediatric Ophthalmology and Strabismus guidelines (≤1500 grams at birth and ≤30 weeks gestation) who develop Stage 3 ROP in zone I or posterior zone II. Informed Consent from a parent or guardian. Exclusion Criteria: Infants who have a congenital systemic anomaly or have a congenital ocular abnormality. Infants who cannot be treated by conventional laser therapy because of problems with media clarity. Generally, blind external cryotherapy would be utilized as an initial therapy and the infant would be excluded from the study even if the media clear subsequently. Informed Consent from a parent or guardian refused. This will mean that an infant automatically will receive laser therapy. Bevacizumab (Avastin®) treatment cannot be given outside of the Protocol. No data will be used from an infant without Informed Consent.

Ages Eligible for Study
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Minimum Age: 4 Weeks
Maximum Age: 22 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bevacizumab for ROP<br>Intravitreal Bevacizumab Therapy is the Experimental Arm of this Study | Drug: Bevacizumab<br>* Anti-angiogenic drug: intravitreal injection of 0.625 mg (0.025 ml) once into each eye.<br>* Other names: Avastin; Monoclonal antibody;|
| Active Comparator: Conventional Laser for ROP<br>Conventional Laser to the Peripheral Retina is the Control Arm of this Study | Procedure: Conventional Laser for ROP<br>* Conventional Laser is applied to the Avascular Peripheral Retina (Anterior to the Vascularized Posterior Retina)<br>* Other names: Diode Laser is the laser utilized for this study;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Eyes Showing Recurrence of Neovascularization Arising From the Retinal Vessels and Requiring Re-treatment | For Bevacizumab: Regrowth of new vessels at the site of the original extraretinal fibrovascular proliferation and/or at the site of the anterior edge of inner retinal vascularization. For Laser: Regrowth of new vessels from the vessels at the anterior edge of inner retinal vascularization (remaining after retinal ablation). | 54 weeks postmenstrual age (window of 50 to 70 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myopia in Zone I and Posterior Zone II of Infant Eyes | Myopia was determined via refraction using a retinoscope and lenses. Myopia is defined as a refractive error reported in Diopters. | 2.5 years of age | 
| Visual Acuity | The visual acuity will be measured at 20 feet with figures or letters from all infants able to cooperate. | Age 7 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vascular Endothelial Growth Factor, Angiogenesis Inhibitor, Premature infants, Bevacizumab, Zone I or Posterior Zone II ROP, Aggressive Posterior ROP, Stage 3 ROP, Neonatal Intensive Care Unit