Diabetic Macular Edema, Non-proliferative Diabetic Retinopathy, Proliferative Diabetic Retinopathy
Conditions
Keywords
Macular Edema, DME, PDR, NPDR, Ozurdex, Dexamethasone, Avastin, Bevacizumab
Brief summary
The purpose of this study is to test the efficacy of an 0.7 mg intravitreal dexamethasone implant (Ozurdex®) on macular leakage and visual acuity for patients with recalcitrant diabetic macular edema.
Detailed description
This is an open-label, Phase II comparative study of an intravitreal dexamethasone implant versus intravitreal bevacizumab (Avastin) in 20 patients with recalcitrant diabetic macular edema and prior treatment with ≥ 2 intravitreal anti-VEGF injections.
Interventions
DRUGdexamethasone intravitreal implant
Ozurdex, 0.7 mg intravitreal dexamethasone implant, given at initial visit and at month 4 (visit 5)
Avastin, 1.25 mg intravitreal bevacizumab, given at initial visit and Q1month for a total of 5 treatments.
Sponsors
Allergan
Retina Macula Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Presence of NPDR or PDR as confirmed by fluorescein angiography * Prior treatment with \>= 2 intravitreal anti-VEGF injections but no treatment in last 4 weeks * \< 0.1 LogOCT decrease in macular edema on high resolution OCT between initial visit and following treatment with \>= 2 intravitreal anti-VEGF injections * Age 18 years or older * ETDRS Visual acuity between 3 and 78 letters (approximate Snellen equivalent of 20/25 to 20/800) * Ability to provide written informed consent * Capable of complying with study protocol.
Exclusion criteria
* Intraocular injection of steroid medication within prior 3 months * Evidence of significant geographic atrophy on fluorescein angiography in the opinion of the treating physician * Concurrent ocular disease (wet AMD, significant ERM, etc) that would limit visual acuity in the opinion of the treating physician * Prior vitrectomy surgery * Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) within 1 month prior to day 1. * Known history of IOP elevation in response to steroid treatment in either eye that resulted in any of the following: a) = 10 mm Hg increase in IOP in response to steroid injection, or b) IOP = 25 mm Hg and required 2 or more anti-glaucoma medications to keep IOP below 21 mm Hg. * Patients who are pregnant. * Unwilling or unable to follow or comply with all study related procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Visual Acuity (Number of ETDRS Letters). | 6 months | The measure the change in ETDRS letters for each treatment group from baseline to 6 months. |
| The Change in Central Foveal Thickness (Microns on High Resolution OCT). | 6 months | The measure the change in central foveal thickness for each treatment group from baseline to 6 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Macular Leakage on Fluorescein Angiography From Baseline | 6 months | To qualitatively assess the change in macular leakage on fluorescein angiography from baseline to 6 months for each treatment arm. |
| The Change in Mean Macular Sensitivity on Microperimetry From Baseline | 6 months | To assess the change in macular sensitivity on microperimetry from baseline to 6 months for each treatment arm. |
| The Change in Mean Central Amplitude on Multi-focal ERG From Baseline. | 6 months | To assess the change in mean central amplitude on multi-focal ERG from baseline to 6 months for each treatment arm. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ozurdex Patients in this group receive Ozurdex at initial visit and at month 4
dexamethasone intravitreal implant: Ozurdex, 0.7 mg intravitreal dexamethasone implant, given at initial visit and at month 4 (visit 5) | 10 |
| Avastin Patients in this group receive Avastin Q1 month for 5 months.
intravitreal bevacizumab: Avastin, 1.25 mg intravitreal bevacizumab, given at initial visit and Q1month for a total of 5 treatments. | 10 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Ozurdex | Avastin | Total |
|---|---|---|---|
| Age, Continuous | 63.9 years STANDARD_DEVIATION 1.8 | 61.2 years STANDARD_DEVIATION 2.9 | 62.6 years STANDARD_DEVIATION 1.7 |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
The Change in Central Foveal Thickness (Microns on High Resolution OCT).
The measure the change in central foveal thickness for each treatment group from baseline to 6 months.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozurdex | The Change in Central Foveal Thickness (Microns on High Resolution OCT). | Baseline | 385.9 microns | Standard Error 43 |
| Ozurdex | The Change in Central Foveal Thickness (Microns on High Resolution OCT). | Final Visit | 305.4 microns | Standard Error 9.1 |
| Avastin | The Change in Central Foveal Thickness (Microns on High Resolution OCT). | Baseline | 341.5 microns | Standard Error 11.3 |
| Avastin | The Change in Central Foveal Thickness (Microns on High Resolution OCT). | Final Visit | 324.3 microns | Standard Error 10.9 |
Primary
The Change in Visual Acuity (Number of ETDRS Letters).
The measure the change in ETDRS letters for each treatment group from baseline to 6 months.
Time frame: 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozurdex | The Change in Visual Acuity (Number of ETDRS Letters). | Baseline | 67.8 ETDRS letters | Standard Error 3.8 |
| Ozurdex | The Change in Visual Acuity (Number of ETDRS Letters). | Final Visit | 69.6 ETDRS letters | Standard Error 4.8 |
| Avastin | The Change in Visual Acuity (Number of ETDRS Letters). | Baseline | 71.9 ETDRS letters | Standard Error 2.9 |
| Avastin | The Change in Visual Acuity (Number of ETDRS Letters). | Final Visit | 72.9 ETDRS letters | Standard Error 3.4 |
Secondary
The Change in Macular Leakage on Fluorescein Angiography From Baseline
To qualitatively assess the change in macular leakage on fluorescein angiography from baseline to 6 months for each treatment arm.
Time frame: 6 months
Population: Fluorescein angiography data were not collected.
Secondary
The Change in Mean Central Amplitude on Multi-focal ERG From Baseline.
To assess the change in mean central amplitude on multi-focal ERG from baseline to 6 months for each treatment arm.
Time frame: 6 months
Population: One patient in the Ozurdex group withdrew consent, one patient in the Avastin group was lost to follow-up, and results were unattainable for three other patients due to testing difficulties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozurdex | The Change in Mean Central Amplitude on Multi-focal ERG From Baseline. | Baseline | 27.8 nV/deg2 | Standard Error 4.3 |
| Ozurdex | The Change in Mean Central Amplitude on Multi-focal ERG From Baseline. | Final Visit | 40.9 nV/deg2 | Standard Error 3.8 |
| Avastin | The Change in Mean Central Amplitude on Multi-focal ERG From Baseline. | Baseline | 34.4 nV/deg2 | Standard Error 11 |
| Avastin | The Change in Mean Central Amplitude on Multi-focal ERG From Baseline. | Final Visit | 30.3 nV/deg2 | Standard Error 6.5 |
Secondary
The Change in Mean Macular Sensitivity on Microperimetry From Baseline
To assess the change in macular sensitivity on microperimetry from baseline to 6 months for each treatment arm.
Time frame: 6 months
Population: One patient in the Ozurdex group withdrew consent, one patient in the Avastin group was lost to follow-up, and results were unattainable for two patients due to imaging difficulties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ozurdex | The Change in Mean Macular Sensitivity on Microperimetry From Baseline | Baseline | 5.6 dB | Standard Error 2 |
| Ozurdex | The Change in Mean Macular Sensitivity on Microperimetry From Baseline | Final Visit | 7.4 dB | Standard Error 1.2 |
| Avastin | The Change in Mean Macular Sensitivity on Microperimetry From Baseline | Baseline | 10.7 dB | Standard Error 2.2 |
| Avastin | The Change in Mean Macular Sensitivity on Microperimetry From Baseline | Final Visit | 10.7 dB | Standard Error 1.5 |