Treatment for CI-DME in Eyes With Very Good VA Study
Protocol V
Treatment for Central-Involved Diabetic Macular Edema in Eyes With Very Good Visual Acuity
4 other identifiers
interventional
702
2 countries
103
Brief Summary
Although multiple studies have clearly demonstrated that ranibizumab therapy is more effective than laser alone for vision gain and avoiding vision loss in patients with central-involved Diabetic Macular Edema (DME), only eyes with poor visual acuity, such as a visual acuity letter score of 78 or worse (approximate Snellen equivalent of 20/32 or worse) were eligible. Eyes that have central-involved DME with "good" visual acuity (20/25 or better) have not been addressed systematically by recent studies for treatment of DME. Baseline cohort characteristics from the Early Treatment Diabetic Retinopathy Study (ETDRS) suggest that a substantial percentage of eyes with central-involved DME may retain good vision. The investigators do not know definitively whether eyes with central-involved DME and good vision do better with anti-VEGF (vascular endothelial growth factor) (e.g. aflibercept) therapy initially, or focal/grid laser treatment or observation initially followed by anti-VEGF only if vision worsens. The primary objective of the protocol is to compare the % of eyes that have lost at least 5 letters of visual acuity at 2 years compared with baseline mean visual acuity in eyes with central-involved DME and good visual acuity defined as a Snellen equivalent of 20/25 or better (electronic-ETDRS letter score of 79 or better) that receive (1) prompt focal/grid photocoagulation + deferred anti-VEGF, (2) observation + deferred anti-VEGF, or (3) prompt anti-VEGF. Secondary objectives include:
- Comparing other visual acuity outcomes between treatment groups, such as the percent of eyes with at least 5, 10 and 15 letter losses in visual acuity from baseline mean visual acuity, percent of eyes with at least 5 letter gain in visual acuity from baseline, mean visual acuity, mean change in visual acuity, adjusted for baseline mean visual acuity
- For eyes randomized to deferred anti-VEGF, the percentage of eyes needing anti-VEGF treatment
- Comparing optical coherence tomography (OCT) outcomes, such as the mean change in OCT central subfield (CSF) thickness, adjusted for baseline mean thickness
- Comparing the number of eyes with PDR at randomization, proportion of eyes avoiding vitreous hemorrhage or panretinal photocoagulation (PRP) or vitrectomy for PDR between treatment groups
- Comparing safety outcomes between treatment groups
- Comparing associated treatment and follow-up exam costs between treatment groups
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2013
Longer than P75 for phase_3
103 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 23, 2013
CompletedFirst Posted
Study publicly available on registry
July 29, 2013
CompletedStudy Start
First participant enrolled
October 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
September 11, 2018
CompletedResults Posted
Study results publicly available
January 3, 2020
CompletedJuly 31, 2020
July 1, 2020
4.9 years
July 23, 2013
September 11, 2019
July 14, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Eyes With at Least 5-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline
Best-corrected visual acuity following protocol-defined refraction. Visual Acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity test on a scale from 100 letters (Snellen equivalent of 20/12) to 0 letters (Snellen equivalent of 20/800).
2 years
Secondary Outcomes (17)
Number of Eyes With at Least 5-letter Increase or at Least 5-, 10-, or 15-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline
1 year
Change in E-ETDRS Visual Acuity Letter Score From Baseline
1 year
Change in E-ETDRS Visual Acuity Letter Score From Baseline Over 2 Years (Area Under the Curve)
2 year
Change in OCT Central Subfield Thickness From Baseline
2 years
Number of Eyes With at Least 1 or 2 Logarithmic-step Central Subfield Thickness Improvement and Worsening
1 year
- +12 more secondary outcomes
Study Arms (3)
Prompt Laser + Deferred Aflibercept
EXPERIMENTALFocal/grid laser followed by intravitreal aflibercept if vision worsens
Observation + Deferred Aflibercept
ACTIVE COMPARATORNo treatment to start followed by intravitreal aflibercept if vision worsens (deferred laser may be added to intravitreal aflibercept if certain criteria are met)
Prompt Aflibercept
EXPERIMENTALIntravitreal aflibercept at baseline and every 4 weeks as needed (deferred laser may be added to intravitreal aflibercept if certain criteria are met)
Interventions
Focal/grid laser performed at baseline and as needed during follow-up
Intravitreal injection of 2.0mg aflibercept performed on the day of randomization and up to every 4 weeks using defined treatment criteria
Focal/grid laser is initiated while receiving anti-VEGF injections only if certain criteria are met
Intravitreal injection of 2.0mg aflibercept performed once certain criteria for vision loss are met and then up to every 4 weeks using defined treatment criteria
Eligibility Criteria
You may qualify if:
- Age \>= 18 years
- Diagnosis of diabetes mellitus (type 1 or type 2)
- Any one of the following will be considered to be sufficient evidence that diabetes is present:
- Current regular use of insulin for the treatment of diabetes
- Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
- Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.
- Able and willing to provide informed consent.
- Meets all of the following ocular criteria in at least the one eye:
- Best corrected E-ETDRS visual acuity letter score ≥ 79 (approximate Snellen equivalent 20/25 or better) at two consecutive visits within 1 to 28 days.
- On clinical exam, definite retinal thickening due to DME involving the center of the macula.
- Diabetic macular edema confirmed on OCT (equivalent to CSF thickness on OCT ≥250 microns on Zeiss Stratus or gender-specific spectral domain OCT equivalent) at two consecutive visits within 1 to 28 days.
- (a) Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality.
- The investigator is comfortable with the eye being randomized to any of the three treatment groups (observation, laser, or anti-VEGF initially).
- (a) If focal/grid photocoagulation is contraindicated because all leaking microaneurysms are too close to the fovea or the investigator believes the DME that is present will not benefit from focal/grid photocoagulation, the eye should not be enrolled.
- Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs.
You may not qualify if:
- History of chronic renal failure requiring dialysis or kidney transplant.
- A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
- Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.
- Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.
- (a) Note: study participants cannot receive another investigational drug while participating in the study.
- Known allergy to any component of the study drug.
- Blood pressure \>180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
- Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.
- These drugs should not be used during the study.
- For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.
- (a) Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.
- Individual is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 24 months of the study.
- Individual has any of the following ocular characteristics:
- Macular edema is considered to be due to a cause other than DME.
- a) An eye should not be considered eligible if: (1) the macular edema is considered to be related to ocular surgery such as cataract extraction or (2) clinical exam and/or OCT suggest that vitreoretinal interface abnormalities (e.g., a taut posterior hyaloid or epiretinal membrane) are contributing to the macular edema.
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jaeb Center for Health Researchlead
- Regeneron Pharmaceuticalscollaborator
- National Eye Institute (NEI)collaborator
- National Institutes of Health (NIH)collaborator
Study Sites (103)
Arizona Retina and Vitreous Consultants
Phoenix, Arizona, 85021, United States
University of Arizona Medical Center/Department of Ophthalmology
Tucson, Arizona, 85711, United States
Jones Eye Institute/University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205-7199, United States
Retinal Diagnostic Center
Campbell, California, 95008, United States
Loma Linda University Health Care, Dept. of Ophthalmology
Loma Linda, California, 92354, United States
South Coast Retina Center
Long Beach, California, 90807, United States
Southern California Desert Retina Consultants, MC
Palm Desert, California, 92211, United States
Retina Consultants of Southern California
Redlands, California, 92374, United States
Retinal Consultants Medical Group, Inc.
Sacramento, California, 95841, United States
California Retina Consultants
Santa Barbara, California, 93103, United States
Bay Area Retina Associates
Walnut Creek, California, 94598, United States
Retinal Consultants of Southern California Medical Group, Inc.
Westlake Village, California, 91361, United States
Retina Group of New England
New London, Connecticut, 06320, United States
New England Retina Associates
Norwich, Connecticut, 06360, United States
National Ophthalmic Research Institute
Fort Myers, Florida, 33912, United States
University of Florida College of Med., Department of Ophthalmology
Jacksonville, Florida, 32209, United States
Florida Retina Consultants
Lakeland, Florida, 33805, United States
Retina Macula Specialists of Miami
Miami, Florida, 33126, United States
Bascom Palmer Eye Institute
Miami, Florida, 33136, United States
Ocala Eye Retina Consultants
Ocala, Florida, 34474, United States
Magruder Eye Institute
Orlando, Florida, 32803, United States
Fort Lauderdale Eye Institute
Plantation, Florida, 33324, United States
Center for Sight
Sarasota, Florida, 34239, United States
Sarasota Retina Institute
Sarasota, Florida, 34239, United States
Retina Associates of Florida, P.A.
Tampa, Florida, 33609, United States
Emory Eye Center
Atlanta, Georgia, 30322, United States
Southeast Retina Center, P.C.
Augusta, Georgia, 30909, United States
Marietta Eye Clinic
Marietta, Georgia, 30060, United States
Thomas Eye Group
Sandy Springs, Georgia, 30328, United States
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611, United States
University of Illinois at Chicago Medical Center
Chicago, Illinois, 60612, United States
NorthShore University HealthSystem
Glenview, Illinois, 60026, United States
Illinois Retina Associates
Joliet, Illinois, 60435, United States
University Retina and Macula Associates
Oak Forest, Illinois, 60452, United States
Carle Foundation Hospital
Urbana, Illinois, 61801, United States
Raj Maturi
Indianapolis, Indiana, 46290, United States
John-Kenyon American Eye Institute
New Albany, Indiana, 47150, United States
Medical Associates Clinic, P.C.
Dubuque, Iowa, 52002, United States
Wolfe Eye Clinic
West Des Moines, Iowa, 50266, United States
University of Kansas Medical Center, Dept. of Ophthalmology
Prairie Village, Kansas, 66208, United States
Retina Associates, P.A.
Shawnee Mission, Kansas, 66204, United States
Retina and Vitreous Associates of Kentucky
Lexington, Kentucky, 40509, United States
Paducah Retinal Center
Paducah, Kentucky, 42001, United States
Elman Retina Group, P.A.
Baltimore, Maryland, 21237, United States
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, 21287-9277, United States
Joslin Diabetes Center
Boston, Massachusetts, 02215, United States
Vitreo-Retinal Associates, PC
Worcester, Massachusetts, 01605, United States
Kellogg Eye Center, University of Michigan
Ann Arbor, Michigan, 48105, United States
Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
Detroit, Michigan, 48202, United States
Retina Vitreous Center
Grand Blanc, Michigan, 48439, United States
Retina Specialists of Michigan
Grand Rapids, Michigan, 49525, United States
Vitreo-Retinal Associates
Grand Rapids, Michigan, 49546, United States
Andersen Eye Associates
Saginaw, Michigan, 48603, United States
Retina Center, PA
Minneapolis, Minnesota, 55404, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic Department of Ophthalmology
Rochester, Minnesota, 55905, United States
Mid-America Retina Consultants, P.A.
Kansas City, Missouri, 64111, United States
The Retina Institute
St Louis, Missouri, 63128, United States
Eyesight Ophthalmic Services, PA
Portsmouth, New Hampshire, 03801, United States
The Institute of Ophthalmology and Visual Science (IOVS)
Newark, New Jersey, 07103, United States
Retinal and Ophthalmic Consultants, PC
Northfield, New Jersey, 08225, United States
Eye Associates of New Mexico
Albuquerque, New Mexico, 87102, United States
Ross Eye Institute, SUNY Buffalo
Buffalo, New York, 14209, United States
The New York Eye and Ear Infirmary/Faculty Eye Practice
New York, New York, 10003, United States
MaculaCare
New York, New York, 10021, United States
Retina Associates of Western New York
Rochester, New York, 14618, United States
University of Rochester
Rochester, New York, 14642, United States
Retina-Vitreous Surgeons of Central New York, PC
Syracuse, New York, 13224, United States
Western Carolina Retinal Associates, PA
Asheville, North Carolina, 28803, United States
University of North Carolina
Chapel Hill, North Carolina, 27599-7040, United States
Charlotte Eye, Ear, Nose and Throat Assoc., PA
Charlotte, North Carolina, 28210, United States
Retina Associates of Cleveland, Inc.
Beachwood, Ohio, 44122, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Retina Vitreous Center
Edmond, Oklahoma, 73013, United States
Oregon Retina, LLP
Eugene, Oregon, 97401, United States
Retina Northwest, PC
Portland, Oregon, 97210, United States
Casey Eye Institute
Portland, Oregon, 97239, United States
Family Eye Group
Lancaster, Pennsylvania, 17601-2644, United States
Retina Vitreous Consultants
Monroeville, Pennsylvania, 15146, United States
University of Pennsylvania Scheie Eye Institute
Philadelphia, Pennsylvania, 19104, United States
Carolina Retina Center
Columbia, South Carolina, 29223, United States
Palmetto Retina Center
West Columbia, South Carolina, 29169, United States
Southeastern Retina Associates
Chattanooga, Tennessee, 37421, United States
Southeastern Retina Associates, PC
Kingsport, Tennessee, 37660, United States
Southeastern Retina Associates, P.C.
Knoxville, Tennessee, 37909, United States
Southwest Retina Specialists
Amarillo, Texas, 79106, United States
Austin Retina Associates
Austin, Texas, 78705, United States
Retina Research Center
Austin, Texas, 78705, United States
Retina and Vitreous of Texas
Houston, Texas, 77025, United States
Baylor Eye Physicians and Surgeons
Houston, Texas, 77030, United States
Retina Consultants of Houston, PA
Houston, Texas, 77030, United States
Texas Retina Associates
Lubbock, Texas, 79424, United States
Valley Retina Institute
McAllen, Texas, 78503, United States
Retinal Consultants of San Antonio
San Antonio, Texas, 78240, United States
Retina Associates of Utah, P.C.
Salt Lake City, Utah, 84107, United States
Retina Institute of Virginia
Richmond, Virginia, 23235, United States
Virginia Commonwealth University, Dept. of Ophthalmology
Richmond, Virginia, 23298, United States
University of Washington Medical Center
Seattle, Washington, 98104, United States
Spokane Eye Clinic
Spokane, Washington, 99204, United States
University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
Madison, Wisconsin, 53705, United States
Alberta Retina Consultants
Edmonton, Alberta, T5H 0X5, Canada
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 258, Canada
UBC/VCHA Eye Care Centre
Vancouver, V5Z 3N9, Canada
Related Publications (2)
Glassman AR, Baker CW, Beaulieu WT, Bressler NM, Punjabi OS, Stockdale CR, Wykoff CC, Jampol LM, Sun JK; DRCR Retina Network. Assessment of the DRCR Retina Network Approach to Management With Initial Observation for Eyes With Center-Involved Diabetic Macular Edema and Good Visual Acuity: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2020 Apr 1;138(4):341-349. doi: 10.1001/jamaophthalmol.2019.6035.
PMID: 32077907BACKGROUNDBaker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, Grover S, Jampol LM, Jhaveri CD, Melia M, Stockdale CR, Martin DF, Sun JK; DRCR Retina Network. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA. 2019 May 21;321(19):1880-1894. doi: 10.1001/jama.2019.5790.
PMID: 31037289RESULT
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Glassman
- Organization
- Jaeb Center for Health Research
Study Officials
- STUDY CHAIR
Carl Baker, MD
Paducah Retina Center
- PRINCIPAL INVESTIGATOR
Adam Glassman, MS
Jaeb Center for Health Research
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 23, 2013
First Posted
July 29, 2013
Study Start
October 1, 2013
Primary Completion
September 11, 2018
Study Completion
September 11, 2018
Last Updated
July 31, 2020
Results First Posted
January 3, 2020
Record last verified: 2020-07