Evaluation of Macugen Treatment of Macular Edema Due to Branch Retinal Vein Occlusion

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of intravitreal injections of Macugen every 6 weeks for the treatment of macular edema secondary to branch retinal vein occlusion (BRVO). We hypothesize that macular edema secondary to BRVO is mediated by VEGF 165 and that chronic suppression of VEGF 165 will successfully treat BRVO related macular edema.

Detailed Description
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Retinal venous occlusive disease, which includes central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), is second only to diabetic retinopathy as a cause of vision loss due to retinal disease. The main cause of vision loss in all of these disorders is the development of macular edema. Current clinical practice based on randomized controlled clinical trials (ETDRS, BVOS) employs laser photocoagulation, either in a focal or grid pattern, to treat macular edema associated with diabetic retinopathy and branch retinal vein occlusion. Unfortunately, laser photocoagulation is ineffective in central retinal vein occlusion (CRVO), and no proven therapy exists for CRVO. The pathogenesis of macular edema in retinal vascular diseases is generally accepted to be increased levels of vascular endothelial growth factor (VEGF) due to ischemic or other stimuli. VEGF is known to be one of the most potent stimulators of vascular leakage in humans. Therefore, it seems sensible to study inhibition of VEGF to reduce vascular leakage, reduce macular edema, and improve vision in these retinal vascular disorders. Phase 2 randomized, controlled clinical trials of Macugen in diabetic macular edema and in macular edema associated with CRVO have been conducted. In the diabetes trial, patients treated with Macugen had improved vision, reduced macular edema as measured by optical coherence tomography (OCT), and reduced need for laser treatment compared to patients treated with sham injections. In the CRVO trial, patients treated with Macugen 1 mg every 6 weeks for 24 weeks had improved vision and reduced macular edema at week 30 compared to sham. This is the first randomized trial of treatment for CRVO to show a benefit over control. Based on these positive findings, we plan to study Macugen treatment of macular edema due to BRVO.

Official Title
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Open Label Macugen for the Treatment of Macular Edema Secondary to Branch Retinal Vein Occlusion

Conditions
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Branch Retinal Vein Occlusion

Intervention / Treatment
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* Drug: pegaptanib sodium (Macugen)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Macular edema secondary to BRVO involving the foveal center in male or female patients at least 18 years of age Duration of BRVO macular edema less than 6 months prior to baseline visit Best corrected ETDRS visual acuity 20/40-20/320 (Snellen equivalent) using the 4 meters testing method. Central foveal thickness greater than or equal to 250 microns using the OCT-3 Less than 25% of foveal capillary ring disruption Less than 2 disc areas of capillary non-perfusion within 1000 microns of the foveal center Absence of hemorrhage or lipid in the foveal center Investigator comfortable deferring macular laser for 18 weeks from baseline and intravitreous steroid for 36 weeks from baseline Exclusion Criteria: Ocular conditions other than BRVO related macular edema such as significant cataract, diabetic retinopathy, AMD, glaucoma, uveitis, epiretinal membrane, vitreomacular traction or tumor. Intraocular surgery within past 3 months Significant enlargement of foveal avascular zone(>25% disruption of capillary ring) or greater than 2 disc areas of nonperfusion within 1000 microns of foveal center. Likelihood of evidence driven indication for peripheral photocoagulation in the next 6 months. Patients who have shown evidence of spontaneous improvement within the preceding 3 months, as determined by an improvement of >15 letters of vision or thinning of the Center Point on OCT of >20% from baseline determination Prior grid laser within 4 months of baseline or more than one prior grid laser treatment. No prior intravitreous or periocular steroid injections in the study eye.

Ages Eligible for Study
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Minimum Age: 18 Years

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 |
| --- | --- |
| Active Comparator: Pegaptanib Sodium 0.3mg (Macugen)<br>Intravitreous injections of Macugen 0.3mg given at baseline, week 6 and week 12 with subsequent injections at six weekly intervals at the discretion of the investigator until week 54. | Drug: pegaptanib sodium (Macugen)<br>* Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3mg or 1mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48.<br>* Other names: Macugen;|
| Active Comparator: Pegaptanib Sodium 1 mg (Macugen)<br>Intravitreous injections of Macugen 1.0mg given at baseline, week 6 and week 12 with subsequent injections at six weekly intervals at the discretion of the investigator until week 54. | Drug: pegaptanib sodium (Macugen)<br>* Subjects were randomized 3:1 to intravitreous injections of pegaptanib 0.3mg or 1mg at baseline and at weeks 6 and 12 with subsequent injections at 6-week intervals at investigator discretion until week 48.<br>* Other names: Macugen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ETDRS Best Corrected Visual Acuity From Baseline at 54 Weeks |  | 54 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Standardized Change From Baseline in Macular Thickening Measured by OCT3 Using the Central Point of the Central Subfield |  | 54 Weeks | 
| Safety Parameters | Safety endpoints incuded all investigator reported ocular and systemic adverse events. All events were graded as mild moderate or severe and assessed as related or unrelated to the injection procedure and the study drug. | 54 Weeks | 
| Change in Central Subfield Thickness on OCT From Baseline to Week 54 |  | 54 Weeks | 
| Change in Macular Volume on OCT From Baseline to Week 54 |  | 54 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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branch retinal vein occlusion, macular edema, pegaptanib sodium, vascular endothelial growth factor