Diabetic Macular Edema
Conditions
Brief summary
Laser photocoagulation and intravitreal anti-vascular growth factor injections are commonly used treatment options for individuals with diabetic macular edema. However, some patients continue to experience persistent diabetic macular edema and poor vision despite continued laser and/or anti-vegf therapy. Recent clinical trials suggest that due to inflammatory mediators dexamethasone intravitreal implant (0.7mg) may be a good alternative therapy for individuals unresponsive to laser photocoagulation or intravitreal anti-vascular growth factor injections. The purpose of this research study is to compare the effectiveness of using a dexamethasone steroid implant versus monthly intravitreal anti-VEGF injections for research participants with persistent diabetic macular edema (DME).
Detailed description
Macular edema is a major cause of central vision loss in patients presenting with diabetic retinopathy. Diabetic macular edema (DME) occurs when fluid leaks into the center of the macula, the part of the eye where sharp, straight-ahead vision occurs. The fluid makes the macula swell, blurring vision. Diabetic macular edema (DME) affects between 8% to 10% of 23.6 million diabetic individuals in the United States. The prevalence of diabetic macular edema after 15 years of known diabetes is approximately 20% in patients with type 1 diabetes, 25% in patients with type 2 diabetes who are taking insulin, and 14% in patients with type 2 diabetes who do not take insulin. Within two years of diagnosis, nearly half of individuals with DME will lose 2 or more lines of visual acuity (the smallest line you can read on a standardized vision chart held 20 feet away). Diabetic macular edema is typically treated with laser and/or intravitreal injections of drugs such as anti-VEGF agents. Anti-VEGF agents block a protein that slows the growth of the abnormal blood vessels. Dexamethasone is a corticosteroid used to treat inflammation. Dexamethasone implant is a steroid implant injected into the eye to treat swelling that may occur when there is a blockage of certain blood vessels in your eyes. Both anti-VEGF agents and dexamethasone implant are approved by the FDA to treat DME. The purpose of this research study is to compare the effectiveness of using a dexamethasone steroid implant versus monthly intravitreal anti-VEGF injections for research participants with persistent diabetic macular edema (DME).
Interventions
DRUGDexamethasone intravitreal implant (0.7 mg)
Subjects with persistent DME who are randomized to this arm may get up to 3 treatments with the implant (0.7 mg dexamethasone).
This injection may be ranibizumab, bevacizumab, or aflibercept.
Sponsors
Allergan
California Retina Consultants
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
* Able to provide written informed consent and comply with study assessments for the full duration of the study. * Age ≥ 18 years * Diagnosis of diabetes mellitus (type 1 or 2) * Any one of the following will be considered to be sufficient evidence that diabetes is present: * Current regular use of insulin for treatment of diabetes * Current regular use of oral anti-hyperglycemia agent for the treatment of diabetes * Clinical evidence of retinal thickening due to macular edema involving the center of the macula associated with diabetic retinopathy. * Previous history of anti-vegf treatment for diabetic macular edema (DME) with documented incomplete resolution of central subfield thickening by spectral-domain optical coherence tomography (SDOCT). At least 4 intravitreal anti-vegf injections within the past six months prior to the baseline study visit are required for eligibility. * Central diabetic macular edema present on clinical examination and SDOCT testing with central 1 mm subfield thickness greater than 300 microns as measured on SDOCT at the baseline visit. * Visual acuity score greater than or equal to 19 letters (20/400) and less than or equal to 74 letters (20/32) by the ETDRS visual acuity protocol. * Media clarity, pupillary dilation and patient cooperation sufficient to allow SDOCT testing and retinal photography.
Exclusion criteria
* Pregnancy (positive pregnancy test) or known to be pregnant; also pre-menopausal women not using adequate contraception. * Participation in another ocular investigation or trial simultaneously * Blood pressure \> 180/110 mmHg (systolic above 180 OR diastolic above 110 mmHg) * Any condition that, in the opinion of the investigator, would preclude participation in the study (e.g. chronic alcoholism, drug abuse) * Evidence of vitreoretinal interface abnormality after ocular exam or OCT that may be contributing to the macular edema * An eye that, in the investigator's opinion, has no chance of improving in visual acuity following resolution of macular edema (e.g. presence of subretinal fibrosis or geographic atrophy) * Presence of another ocular condition that may affect the visual acuity or macular edema during the course of the study (e.g. AMD, uveitis, Irvine-Gass) * Evidence of active neovascularization of the iris or retina * Evidence of central atrophy or fibrosis in the study eye * Presence of substantial cataract, one that might decrease the vision by 3 or more lines of vision at sometime during the study. * History of vitreous surgery in the study eye * History of cataract surgery within 3 months of enrollment. * History of YAG capsulotomy within 2 months of enrollment. * Visual acuity \<20/400 on ETDRS visual acuity charts in the fellow eye * Uncontrolled glaucoma (pressure \> 30 mmHg) despite treatment with glaucoma medications. * History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0. * Use of systemic steroids (eg, oral, intravenous, intramuscular, epidural, rectal, or extensive dermal) within one month prior to the baseline study visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months | baseline and 9 months | Mean change in central 1 mm sub-field thickness between baseline and 9 months as measured by Spectral Domain Optical Coherence Tomography (SDOCT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months | baseline and 9 months | Mean change in standardized best-corrected visual acuity between baseline and 9 months as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified |
| Total Number of Treatments in Each Arm Between Baseline and 9 Months | baseline and 9 months | Total number of treatments in each arm between baseline and 9 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Implant Subjects randomized to dexamethasone intravitreal implant (0.7mg) will receive the initial treatment at Month 3 (visit 4) and Month 6 (visit 7) and are eligible to receive one additional dose at Month 9 (visit 10), Month 10 (visit 11) or Month 11 (visit 12) for persistent or recurrent macular edema documented on SDOCT. If dexamethasone intravitreal implant (0.7mg) is administered at Month 10 (visit 11) or Month 11 (visit 12) an additional safety study visit will be required at one to two months following Month 12 (visit 13). The investigator can withhold treatment with dexamethasone intravitreal implant (0.7mg) beginning at Month 9 if there is complete resolution of diabetic macular edema document on SDOCT.
Dexamethasone intravitreal implant (0.7 mg): Subjects with persistent DME who are randomized to this arm may get up to 3 treatments with the implant (0.7 mg dexamethasone). | 20 |
| Intravitreal Anti-VEGF Injection Subjects randomized to continue on anti-vegf therapy will receive intravitreal anti-vegf injections at Month 3 (visit 4) Month 4 (visit 5) and Month 5 (visit 6). Beginning at Month 6 (visit 7), subjects who have received 6 intravitreal anti-vegf injections and continue to present with persistent diabetic macular edema defined as less than 10% reduction or any increase in CST compared to baseline values and CST is greater than 300 microns, will receive dexamethasone intravitreal implant (0.7mg) at Month 6 (visit 7) and Month 9 (visit 10). The follow-up period for all subjects will continue through 12 months from the baseline study visit.
Intravitreal anti-VEGF injection: This injection may be ranibizumab, bevacizumab, or aflibercept. | 20 |
| Total | 40 |
Baseline characteristics
| Characteristic | Implant | Intravitreal Anti-VEGF Injection | Total |
|---|---|---|---|
| Age, Continuous | 62 years STANDARD_DEVIATION 8 | 65 years STANDARD_DEVIATION 7 | 63 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 7 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 14 Participants | 15 Participants | 29 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 20 |
| other Total, other adverse events | 10 / 20 | 6 / 20 |
| serious Total, serious adverse events | 1 / 20 | 1 / 20 |
Outcome results
Primary
Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months
Mean change in central 1 mm sub-field thickness between baseline and 9 months as measured by Spectral Domain Optical Coherence Tomography (SDOCT).
Time frame: baseline and 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Implant | Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months | -51 millimeters | Standard Deviation 117 |
| Intravitreal Anti-VEGF Injection | Mean Change in Central 1 mm Subfield Thickness Between Baseline and 9 Months | -60 millimeters | Standard Deviation 149 |
Secondary
Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months
Mean change in standardized best-corrected visual acuity between baseline and 9 months as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) testing. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified
Time frame: baseline and 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Implant | Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months | 1.5 letters on the ETDRS scale | Standard Deviation 13 |
| Intravitreal Anti-VEGF Injection | Mean Change in Standardized Best-corrected Visual Acuity (BCVA) Between Baseline and 9 Months | 1.8 letters on the ETDRS scale | Standard Deviation 12 |
Secondary
Total Number of Treatments in Each Arm Between Baseline and 9 Months
Total number of treatments in each arm between baseline and 9 months.
Time frame: baseline and 9 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Implant | Total Number of Treatments in Each Arm Between Baseline and 9 Months | 43 injections |
| Intravitreal Anti-VEGF Injection | Total Number of Treatments in Each Arm Between Baseline and 9 Months | 83 injections |