Conditions: Diabetic Macular Edema
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 40
Healthy volunteers: no

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).

Arms:
arm 1: 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. arm 2: 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.

Interventions: intervention 1: Dexamethasone intravitreal implant (0.7 mg) intervention 2: Intravitreal anti-VEGF injection
Intervention descriptions: intervention 1: Subjects with persistent DME who are randomized to this arm may get up to 3 treatments with the implant (0.7 mg dexamethasone). intervention 2: This injection may be ranibizumab, bevacizumab, or aflibercept.

Protocol document:
Prot_SAP_000.pdf: 
Dexamethasone Intravitreal Implant (0.7mg) for 
the Treatment of Persistent Diabetic Macular 
Edema Following Intravitreal Anti-Vascular 
Endothelial Growth Factor Therapy (DIME Trial) 
 
 
 
NCT #: NCT02471651 
 
Date of Document: 28-OCT-2015 
 
 
 
 
 
 
 
 


STUDY DESIGN 
DESCRIPTION OF THE STUDY 
This is a pilot study of dexamethasone intravitreal implant (0.7mg) in 
subjects with clinical, angiographic and spectral-domain optical coherence 
tomography (SDOCT) evidence of persistent diabetic macular edema 
following intravitreal anti-vascular endothelial growth factor (anti-vegf) 
treatment.  Forty patients will be enrolled in this study. 
 
Consented subjects will receive anti-vegf therapy (aflibercept, 
bevacizumab or ranibizumab) administered every 30 days (±7 days) 
during the run-in phase at baseline, month 1, and month 2. Subjects will 
receive the same anti-vegf medication throughout the run-in phase. 
Subjects with less than 10% reduction or any increase in central 1mm 
subfield thickness (CST) compared to baseline values and CST is greater 
than 300 microns or subjects with any reduction in CST, but whose CST 
remains above 350 microns with concurrent and persistent DME as 
measured on SDOCT following the run-in phase, will be randomized 1:1 
to receive either dexamethasone intravitreal implant (0.7mg) or continue 
on the same anti-vegf therapy.   
 
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.  
 
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. 


 
The primary outcome endpoint is 9 months from randomization (Month 12 
from day of enrollment). The total length of follow-up is 12 months. All 
subjects will make monthly visits for 12 months for evaluation of safety 
and efficacy.  All subjects will have their first intravitreal injection at 
Baseline/Day 0 study visit. At subsequent visits, the subject will have a 
safety evaluation at the monthly scheduled follow-up visit prior to any 
intravitreal injection.   
 
Statistical Analysis Plan 
Mean change in CST and best corrected visual acuity (BCVA) will be assessed by 
an unpaired Student’s t-test.  Total number of injections in each arm will be 
given as a number.