Branch Retinal Vein Occlusion
Conditions
Keywords
branch retinal vein occlusion, macular edema, pegaptanib sodium, vascular endothelial growth factor
Brief summary
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
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.
Interventions
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.
Sponsors
Pfizer
Eyetech Pharmaceuticals
Palmetto Retina Center, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in ETDRS Best Corrected Visual Acuity From Baseline at 54 Weeks | 54 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Standardized Change From Baseline in Macular Thickening Measured by OCT3 Using the Central Point of the Central Subfield | 54 Weeks | — |
| Safety Parameters | 54 Weeks | 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. |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pegaptanib Sodium 0.3mg (Macugen) 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. | 15 |
| Pegaptanib Sodium 1 mg (Macugen) Intravitreous injections of Macugen 1.0 mg given at baseline, week 6 and week 12 with subsequent injections at six weekly intervals at the discretion of the investigator until week 54. | 5 |
| Total | 20 |
Baseline characteristics
| Characteristic | Pegaptanib Sodium 1 mg (Macugen) | Pegaptanib Sodium 0.3mg (Macugen) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 12 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 3 Participants | 3 Participants |
| Age, Continuous | 77 years STANDARD_DEVIATION 8.7 | 72.9 years STANDARD_DEVIATION 8.2 | 73.9 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 5 participants | 15 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 7 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 15 | 0 / 5 |
| serious Total, serious adverse events | 0 / 15 | 0 / 5 |
Outcome results
Primary
Change in ETDRS Best Corrected Visual Acuity From Baseline at 54 Weeks
Time frame: 54 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants | Change in ETDRS Best Corrected Visual Acuity From Baseline at 54 Weeks | 14 ETDRS letters | Standard Deviation 13 |
Secondary
Change in Central Subfield Thickness on OCT From Baseline to Week 54
Time frame: 54 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants | Change in Central Subfield Thickness on OCT From Baseline to Week 54 | -201 microns | Standard Deviation 153 |
Secondary
Change in Macular Volume on OCT From Baseline to Week 54
Time frame: 54 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants | Change in Macular Volume on OCT From Baseline to Week 54 | -2.2 mm cubed | Standard Deviation 1.6 |
Secondary
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.
Time frame: 54 Weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Study Participants | Safety Parameters | 6.67 percentage of participants |
| Pegaptanib Sodium 1 mg (Macugen) | Safety Parameters | 0 percentage of participants |
Secondary
Standardized Change From Baseline in Macular Thickening Measured by OCT3 Using the Central Point of the Central Subfield
Time frame: 54 Weeks
Population: Fifteen patients were enrolled in the pegaptanib 0.3 mg dose group and 5 patients were enrolled in the 1.0 mg dose group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Study Participants | Standardized Change From Baseline in Macular Thickening Measured by OCT3 Using the Central Point of the Central Subfield | -205 microns | Standard Deviation 195 |