Anti-VEGF Treatment for Prevention of PDR/DME
Intravitreous Anti-Vascular Endothelial Growth Factor Treatment for Prevention of Vision Threatening Diabetic Retinopathy in Eyes at High Risk
4 other identifiers
interventional
399
2 countries
85
Brief Summary
Multiple studies have implicated vascular endothelial growth factor VEGF as a major causative factor in human eye diseases characterized by neovascularization including proliferative diabetic retinopathy (PDR) and vascular permeability including diabetic macular edema (DME). While there is strong evidence that PDR outcomes are markedly reduced in eyes that are treated with monthly anti-VEGF therapy (A Study of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema (ME) With Center Involvement Secondary to Diabetes Mellitus: RIDE/RISE) and moderately reduced in eyes that received fairly frequent dosing during the 1st year of treatment (Diabetic Retinopathy Clinical Research Network protocol I), it is unknown whether or not an earlier but less frequent dosing regimen would result in similar, favorable anatomic outcomes, and whether favorable anatomic outcomes subsequently would result in favorable visual acuity outcomes. If this study demonstrates that intravitreous aflibercept treatment is effective and safe for reducing the onset of PDR or center involved- DME (CI-DME) in eyes that are at high risk for these complications, a new strategy to prevent vision threatening complications of diabetes will be available for patients. The application of intravitreous aflibercept earlier in the course of disease (i.e., at the time when an eye has baseline severe non-proliferative diabetic retinopathy) could help to reduce future potential treatment burden in patients, at the same time resulting in similar or better long-term visual outcomes, if PDR and DME are prevented. The primary objectives of this protocol are to 1) determine the efficacy and safety of intravitreous aflibercept injections versus sham injections (observation) for prevention of PDR or CI-DME in eyes at high risk for development of these complications and 2) compare long-term visual outcomes in eyes that receive anti-VEGF therapy early in the course of disease with those that are observed initially, and treated only if high-risk PDR or CI-DME with vision loss develops. Secondary objectives include:
- Comparing other visual acuity outcomes between treatment groups, such as proportion of eyes with at least 10 or at least 15 letter loss from baseline, or gain or loss of at least 5 letters at the consecutive study visit just before and at the 2- or 4-year visit
- Comparing optical coherence tomography (OCT) outcomes, such as mean change in OCT central subfield thickness and volume from baseline
- Comparing proportion of eyes with at least 2 and 3-step worsening or improvement of diabetic retinopathy severity level (scale for individual eyes) by central reading center from baseline
- Comparing associated treatment and follow-up exam costs between treatment groups
- Comparing safety outcomes between treatment groups
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jan 2016
Longer than P75 for phase_3
85 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
December 11, 2015
CompletedFirst Posted
Study publicly available on registry
December 18, 2015
CompletedStudy Start
First participant enrolled
January 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2020
CompletedResults Posted
Study results publicly available
November 24, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 11, 2022
CompletedJune 18, 2023
May 1, 2023
4.3 years
December 11, 2015
June 21, 2021
May 22, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Development of PDR and/or DME (Whichever Came First)
CI-DME = center-involved diabetic macular edema, PDR = proliferative diabetic macular edema. First development of criteria meeting end point. Eyes that met any criteria are then censored from contributing to the next criteria. Eyes that did not meet the outcome were censored at the time of the last completed visit. Each outcome appears only once under "First PDR and/or DME criteria met." Outcomes appear under "Development of PDR" if PDR developed at any time in the study (regardless of if or when DME developed) and outcomes appear under "Development of DME" if DME developed at any time in the study (regardless of if or when PDR developed)
2 years
Change in Visual Acuity From Baseline
Visual acuity is measured as a continuous integer letter score from 0 to 100, with higher numbers indicating better visual acuity. A letter score of 85 is approximately 20/20 and a letter score of 70 is approximately 20/40, the legal unrestricted driving limit in most states. A 5-letter change for an individual is approximately equal to a 1-line change on a vision chart.
2 years
Secondary Outcomes (2)
Change in Visual Acuity From Baseline
4 years
Development of PDR and/or DME (Whichever Came First)
4 years
Study Arms (2)
Observation (Prompt Sham)
SHAM COMPARATORSham injection in study eye at randomization and at visits at 1, 2, and 4 months and then every 4 months thereafter. Deferred aflibercept may be given if center-involved diabetic macular edema or proliferative diabetic retinopathy develops and deferred laser may subsequently be added to intravitreal aflibercept if certain criteria are met.
Prompt aflibercept
EXPERIMENTALAflibercept injection in study eye at randomization and at visits at 1, 2, and 4 months and then every 4 months thereafter. More frequent aflibercept may be given if center-involved diabetic macular edema or proliferative diabetic retinopathy develops and deferred laser may subsequently be added to intravitreal aflibercept if certain criteria are met.
Interventions
A sham injection (syringe without a needle pressed against the injection site) is performed on the day of randomization and visits at 1, 2, and 4 months and then every 4 months thereafter.
Intravitreal injection of 2.0mg aflibercept is performed on the day of randomization and visits at 1, 2, and 4 months and then every 4 months thereafter.
Laser (either focal/grid laser for diabetic macular edema or panretinal photocoagulation for proliferative diabetic retinopathy) is added following initiation of anti-vascular endothelial growth factor injections for center-involved diabetic macular edema or proliferative diabetic retinopathy only if certain criteria are met
Intravitreal injection of 2.0mg aflibercept performed once proliferative diabetic retinopathy or center-involved diabetic macular edema develops 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 and/or World Health Organization criteria
- Able and willing to provide informed consent.
- Meets all of the following ocular criteria in at least one eye:
- Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity letter score ≥79 (approximate Snellen equivalent 20/25 or better)
- Severe NPDR is defined as:
- All 4 midperipheral quadrants show severe hemorrhages or microaneurysms (at least as great as Standard photograph 2A, approximately 20 dot and blot hemorrhages), or
- At least 2 fields of definite venous beading in the midperipheral quadrants or at least 1 field at least as severe as Standard photograph 6A, or
- At least 1 field of moderate intraretinal microvascular abnormalities (IRMA) in the midperipheral quadrants, at least as severe as Standard photograph 8A
- No evidence of neovascularization (NV) on fluorescein angiography within the 7-modified ETDRS fields, confirmed by the central Reading Center prior to randomization.
- No center-involved diabetic macular edema (CI-DME) on clinical exam and optical coherence tomography (OCT) central subfield thickness must be below the following gender and OCT-machine specific thresholds:
- +6 more criteria
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 that involved treatment within 30 days of randomization with any drug that has not received regulatory approval for the indication being studied.
- Note: study participants cannot participate in another investigational trial that involves treatment with an investigational drug while participating in the study.
- Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine prep).
- Known allergy to fluorescein dye.
- 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 2 years.
- 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 Diabetic Retinopathy Clinical Research Network certified clinical center during the next 2 years.
- Individual has any of the following ocular characteristics in the eye(s) being evaluated:
- Exam or photographic evidence of vitreous hemorrhage or preretinal hemorrhage presumed to be from PDR.
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Jaeb Center for Health Researchlead
- Regeneron Pharmaceuticalscollaborator
- Juvenile Diabetes Research Foundationcollaborator
- National Eye Institute (NEI)collaborator
- National Institutes of Health (NIH)collaborator
Study Sites (85)
Arizona Retina and Vitreous Consultants
Phoenix, Arizona, 85021, United States
University of Arizona Medical Center/Department of Ophthalmology
Tucson, Arizona, 85711, United States
Atlantis Eye Care
Huntington Beach, California, 92647, United States
Loma Linda University Health Care, Department of Ophthalmology
Loma Linda, California, 92354, United States
East Bay Retina Consultants, Inc.
Oakland, California, 94609, United States
Southern California Desert Retina Consultants, MC
Palm Desert, California, 92211, United States
Shashi D Ganti, MD PC
Porterville, California, 93257, United States
Retina Consultants of Southern California
Redlands, California, 92374, United States
U.C. Davis Eye Center
Sacramento, California, 95817, United States
California Retina Consultants
Santa Barbara, California, 93103, United States
Retinal Consultants of Southern California Medical Group, Inc.
Westlake Village, California, 91361, United States
New England Retina Associates
Hamden, Connecticut, 06518, United States
Retina Group of Florida
Fort Lauderdale, Florida, 33308, United States
National Ophthalmic Research Institute
Fort Myers, Florida, 33912, United States
University of Florida College of Med., Department of Ophthalmology, Jacksonville Health Science Cent
Jacksonville, Florida, 32209, United States
Florida Retina Institute-Jacksonville
Jacksonville, Florida, 32216, United States
Florida Retina Consultants
Lakeland, Florida, 33805, United States
Bascom Palmer Eye Institute
Miami, Florida, 33136, United States
Magruder Eye Institute
Orlando, Florida, 32803, United States
Florida Retina Institute
Orlando, Florida, 32806, United States
Southeast Eye Institute, P.A. dba Eye Associates of Pinellas
Pinellas Park, Florida, 33782, United States
Fort Lauderdale Eye Institute
Plantation, Florida, 33324, 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
Gailey Eye Clinic
Bloomington, Illinois, 61704, United States
Northwestern Medical Faculty Foundation
Chicago, Illinois, 60611, United States
University of Illinois at Chicago Medical Center
Chicago, Illinois, 60612, United States
Springfield Clinic, LLP
Springfield, Illinois, 62703, United States
Raj K. Maturi, M.D., P.C.
Indianapolis, Indiana, 46290, United States
Medical Associates Clinic, P.C.
Dubuque, Iowa, 52002, United States
Wolfe Eye Clinic
West Des Moines, Iowa, 50266, United States
Retina Associates, P.A.
Shawnee Mission, Kansas, 66204, United States
Paducah Retinal Center
Paducah, Kentucky, 42001, United States
Eye Associates of Northeast Louisiana dba Haik Humble Eye Center
West Monroe, Louisiana, 71291, United States
Elman Retina Group, P.A.
Baltimore, Maryland, 21237, United States
Wilmer Eye Institute at Johns Hopkins
Baltimore, Maryland, 21287, United States
Mid Atlantic Retina Specialists
Hagerstown, Maryland, 21740, United States
Valley Eye Physicians and Surgeons
Ayer, Massachusetts, 01432, United States
Joslin Diabetes Center
Boston, Massachusetts, 02215, United States
Henry Ford Health System, Dept of Ophthalmology and Eye Care Services
Detroit, Michigan, 48202, United States
Vitreo-Retinal Associates
Grand Rapids, Michigan, 49546, United States
Retina Center, PA
Minneapolis, Minnesota, 55404, United States
Mid-America Retina Consultants, P.A.
Kansas City, Missouri, 64111, United States
Retinal and Ophthalmic Consultants, PC
Northfield, New Jersey, 08225, United States
Eye Associates of New Mexico
Albuquerque, New Mexico, 87109, 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
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 Clinical Research, LLC
Asheville, North Carolina, 28803, United States
Kittner Eye Center
Chapel Hill, North Carolina, 27517, 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
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, 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
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, 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
Robert E. Torti, MD, PA dba Retina Specialists
DeSoto, Texas, 75115, United States
Retina Center of Texas
Grapevine, Texas, 76051, 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 Institute of Virginia
Richmond, Virginia, 23235, United States
Virginia Commonwealth University, Dept. of Ophthalmology
Richmond, Virginia, 23298, United States
University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service
Madison, Wisconsin, 53705, United States
UBC/VCHA Eye Care Centre
Vancouver, British Columbia, V5Z 3N9, Canada
Nova Scotia District Health Authority
Halifax, Nova Scotia, B3H 2Y9, Canada
Toronto Retina Institute (TRI)
North York, Ontario, M3C 0G9, Canada
University Health Network - Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Related Publications (2)
Maturi RK, Glassman AR, Josic K, Baker CW, Gerstenblith AT, Jampol LM, Meleth A, Martin DF, Melia M, Punjabi OS, Rofagha S, Salehi-Had H, Stockdale CR, Sun JK; DRCR Retina Network. Four-Year Visual Outcomes in the Protocol W Randomized Trial of Intravitreous Aflibercept for Prevention of Vision-Threatening Complications of Diabetic Retinopathy. JAMA. 2023 Feb 7;329(5):376-385. doi: 10.1001/jama.2022.25029.
PMID: 36749332DERIVEDMaturi RK, Glassman AR, Josic K, Antoszyk AN, Blodi BA, Jampol LM, Marcus DM, Martin DF, Melia M, Salehi-Had H, Stockdale CR, Punjabi OS, Sun JK; DRCR Retina Network. Effect of Intravitreous Anti-Vascular Endothelial Growth Factor vs Sham Treatment for Prevention of Vision-Threatening Complications of Diabetic Retinopathy: The Protocol W Randomized Clinical Trial. JAMA Ophthalmol. 2021 Jul 1;139(7):701-712. doi: 10.1001/jamaophthalmol.2021.0606.
PMID: 33784735DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Glassman
- Organization
- JAEB CENTER FOR HEALTH RESEARCH
Study Officials
- STUDY CHAIR
Jennifer K. Sun, MD, MPH
Joslin Diabetes Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 11, 2015
First Posted
December 18, 2015
Study Start
January 1, 2016
Primary Completion
May 1, 2020
Study Completion
May 11, 2022
Last Updated
June 18, 2023
Results First Posted
November 24, 2021
Record last verified: 2023-05