Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema
- Conditions
- Diabetic RetinopathyDiabetic Macular Edema
- Interventions
- Drug: Sham injection + laser
- Registration Number
- NCT00444600
- Lead Sponsor
- Jaeb Center for Health Research
- Brief Summary
The purpose of the study is to find out which is a better treatment for diabetic macular edema (DME): laser alone, laser combined with an intravitreal injection of triamcinolone, laser combined with an intravitreal injection of ranibizumab, or intravitreal injection of ranibizumab alone. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections, with or without laser treatment, are better than just laser by itself. It is possible that one or both of the types of injections, with or without laser treatment, will improve vision more often than will laser without injections. However, even if better vision outcomes are seen with injections, side effects may be more of a problem with the injections than with laser. Therefore, this study is conducted to find out whether the benefits of the injections will outweigh the risks.
- Detailed Description
Thus far the only demonstrated means to reduce the risk of vision loss from diabetic macular edema are laser photocoagulation, intensive glycemic control, and blood pressure control. Earlier studies have shown that photocoagulation, although effective in reducing the risk of moderate vision loss, can eventually result in retinal and retinal pigment epithelium atrophy resulting in loss of central vision, central scotomata, and decreased color vision. Consequently, many retinal specialists today tend to treat diabetic macular edema (DME) with lighter, less intense laser burns than was originally specified in the Early Treatment Diabetic Retinopathy Study (ETDRS). The additional unsatisfactory outcome from treatments with laser photocoagulation in a significant proportion of eyes with DME has prompted interest in other treatment modalities. One such treatment is pars plana vitrectomy. Studies suggest that vitreomacular traction may play a role in increased retinal vascular permeability, and that removal of the vitreous, or relief of mechanical traction with vitrectomy and membrane stripping may substantially improve macular edema and visual acuity. However, this treatment may be applicable only to a specific subset of eyes with a component of vitreomacular traction secondary to edema. Other treatment modalities such as pharmacologic therapy with oral protein kinase C inhibitors and intravitreal corticosteroids are under investigation.
The use of antibodies targeted at vascular endothelial growth factor (VEGF) is another treatment modality that needs to be further explored for its potential benefits. Increased VEGF levels have been demonstrated in the retina and vitreous of human eyes with diabetic retinopathy. VEGF, also knows as vascular permeability factor, has been shown to increase retinal vascular permeability in in vivo models. Therapy that inhibits VEGF, therefore, may represent a useful therapeutic modality which targets the underlying pathogenesis of diabetic macular edema. Ranibizumab is a promising anti-VEGF drug. Its efficacy and safety have been demonstrated in treatment of age-related macular degeneration. Reports of its use and that of other anti-VEGF drugs in DME have suggested sufficient benefit to warrant evaluation of efficacy and safety in a phase III trial. Corticosteroids, a class of substances with anti-inflammatory properties, have also been demonstrated to inhibit the expression of the VEGF gene. The Diabetic Retinopathy Clinical Research Network (DRCR.net) is currently conducting a phase III randomized clinical trial comparing focal photocoagulation to intravitreal corticosteroids (triamcinolone acetonide) for diabetic macular edema. However, even if triamcinolone or ranibizumab are proven to be efficacious, a major concern, based on clinical observations with intravitreal corticosteroids, is that DME will recur as the effect of the intravitreal drug wears off, necessitating repetitive injections long-term. Combining an intravitreal drug (triamcinolone or ranibizumab) with photocoagulation provides hope that one could get the short-term benefit of the intravitreal drug (decreased retinal thickening and decreased fluid leakage) and the long-term reduction in fluid leakage as a result of photocoagulation. In addition, it is possible that the worsening of macular edema immediately following focal photocoagulation, a known complication of this treatment, could be decreased if an intravitreal drug was present at the time of photocoagulation. This might result in an increased likelihood of vision improvement following photocoagulation and a decreased likelihood of vision loss.
This study is designed to determine if ranibizumab alone or ranibizumab added to laser photocoagulation is more efficacious than photocoagulation alone, and if so, to determine if combining ranibizumab with photocoagulation reduces the total number of injections needed to obtain these benefits. Furthermore, this study is designed to determine if combining photocoagulation with corticosteroids, the only other class of drugs currently being considered for treatment of DME, is efficacious in the population being enrolled.
Subjects will be randomly assigned to one of the following 4 groups:
1. Group A: Sham injection plus focal (macular) photocoagulation
2. Group B: 0.5 mg injection of intravitreal ranibizumab plus focal photocoagulation
3. Group C: 0.5 mg injection of intravitreal ranibizumab plus deferred focal photocoagulation
4. Group D: 4 mg intravitreal triamcinolone plus focal photocoagulation
In groups A, B and D, laser will be given 7-10 days after the initial injection at the time of the injection follow-up safety visit. During the first year, subjects are evaluated for retreatment every 4 weeks. The injection for group A is a sham and for groups B and C ranibizumab. For group D, a triamcinolone injection is given if one has not been given in the prior 15 weeks; otherwise a sham injection is given. For Groups A, B, and D, focal photocoagulation will be given 7 to 10 days later following each injection unless focal photocoagulation has been given in the past 15 weeks or no macular edema is present. In Years 2 and 3, subjects continue to be evaluated for retreatment every 4 weeks unless injections are discontinued due to failure. In that case, follow-up visits occur every 4 months and treatment is at investigator discretion.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 691
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 0.5mg Ranibizumab plus laser Ranibizumab + laser - 0.5 mg Ranibizumab plus deferred laser Ranibizumab + deferred laser - Sham plus laser Sham injection + laser - 4 mg Triamcinolone plus laser Triamcinolone Acetonide + laser -
- Primary Outcome Measures
Name Time Method Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema from baseline to 1 Year Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity from baseline to 1 Year Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year from baseline to 1 Year Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.
Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline from baseline to 1 Year Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score from baseline to 1 Year Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness from baseline to 1 Year Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator from baseline to 1 Year Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity from baseline to 1 Year Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.
- Secondary Outcome Measures
Name Time Method Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year from baseline to 1 Year Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year from baseline to 1 year Negative change denotes an improvement.
Number of Injections in First Year from baseline to 1 year Maximum possible number of injections for each of the following groups: sham+prompt laser=13 sham injections;ranibizumab+prompt laser=13 ranibizumab injections; ranibizumab+deferred laser=13 ranibizumab injections; triamcinolone+prompt laser=4 triamcinolone injections and 9 sham injections.
Number of Laser Treatments Received Prior to the 1 Year Visit 1 Year One eye in the sham+prompt laser group did not receive laser until post 1-year due to an adverse event unrelated to study treatment. One eye in the triamcinolone+prompt laser did not receive laser until after 1-year due to missing 2 consecutive visits at the time of required laser treatment.
Percentage of Eyes Receiving Laser at the 48 Week Visit (%) 1 Year Mean Optical Coherence Tomography Retinal Volume at 1 Year 1 Year
Trial Locations
- Locations (49)
Retina Consultants of Southwest Florida
🇺🇸Fort Myers, Florida, United States
Southeastern Retina Associates, P.C.
🇺🇸Knoxville, Tennessee, United States
Elman Retina Group, P.A.
🇺🇸Baltimore, Maryland, United States
Wilmer Eye Institute at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Ophthalmic Consultants of Boston
🇺🇸Boston, Massachusetts, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Retina Consultants of Delmarva, P.A.
🇺🇸Salisbury, Maryland, United States
Paducah Retinal Center
🇺🇸Paducah, Kentucky, United States
Medical Associates Clinic, P.C.
🇺🇸Dubuque, Iowa, United States
Carolina Retina Center
🇺🇸Columbia, South Carolina, United States
Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
Retina and Vitreous Associates of Kentucky
🇺🇸Lexington, Kentucky, United States
Charlotte Eye, Ear, Nose and Throat Assoc., PA
🇺🇸Charlotte, North Carolina, United States
Palmetto Retina Center
🇺🇸Columbia, South Carolina, United States
Retina Research Center
🇺🇸Austin, Texas, United States
Retina-Vitreous Surgeons of Central New York, PC
🇺🇸Syracuse, New York, United States
Vitreoretinal Consultants
🇺🇸Houston, Texas, United States
Eyesight Ophthalmic Services, PA
🇺🇸Portsmouth, New Hampshire, United States
University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
🇺🇸Madison, Wisconsin, United States
Texas Retina Associates
🇺🇸Lubbock, Texas, United States
The New York Eye and Ear Infirmary/Faculty Eye Practice
🇺🇸New York, New York, United States
Casey Eye Institute
🇺🇸Portland, Oregon, United States
Raj K. Maturi, M.D., P.C.
🇺🇸Indianapolis, Indiana, United States
Retina Center, PA
🇺🇸Minneapolis, Minnesota, United States
University of Florida College of Med., Department of Ophthalmology
🇺🇸Jacksonville, Florida, United States
John-Kenyon American Eye Institute
🇺🇸New Albany, Indiana, United States
Retina Northwest, PC
🇺🇸Portland, Oregon, United States
Sall Research Medical Center
🇺🇸Artesia, California, United States
Loma Linda University Health Care, Dept. of Ophthalmology
🇺🇸Loma Linda, California, United States
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Southern California Desert Retina Consultants, MC
🇺🇸Palm Springs, California, United States
Bay Area Retina Associates
🇺🇸Walnut Creek, California, United States
California Retina Consultants
🇺🇸Santa Barbara, California, United States
Southeastern Retina Associates, PC
🇺🇸Kingsport, Tennessee, United States
West Texas Retina Consultants P.A.
🇺🇸Abilene, Texas, United States
Retina and Vitreous of Texas
🇺🇸Houston, Texas, United States
Retina Vitreous Consultants
🇺🇸Fort Lauderdale, Florida, United States
Retina Associates of Cleveland, Inc.
🇺🇸Beachwood, Ohio, United States
Penn State College of Medicine
🇺🇸Hershey, Pennsylvania, United States
Central Florida Retina Institute
🇺🇸Lakeland, Florida, United States
Southeast Retina Center, P.C.
🇺🇸Augusta, Georgia, United States
Illinois Retina Associates
🇺🇸Joliet, Illinois, United States
University of Pennsylvania Scheie Eye Institute
🇺🇸Philadelphia, Pennsylvania, United States
Retina Consultants
🇺🇸Providence, Rhode Island, United States
University of California, Irvine
🇺🇸Irvine, California, United States
Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
University of North Carolina, Dept of Ophthalmology
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Eye Center
🇺🇸Winston-Salem, North Carolina, United States