Treatment for CI-DME in Eyes With Very Good VA Study

NCT ID: NCT01909791

Last Updated: 2020-07-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 702 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2018-09-11

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

Conditions

Diabetic Macular Edema

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Prompt Laser + Deferred Aflibercept

Focal/grid laser followed by intravitreal aflibercept if vision worsens

Group Type: EXPERIMENTAL

Prompt Laser

Intervention Type: PROCEDURE

Focal/grid laser performed at baseline and as needed during follow-up

Deferred aflibercept

Intervention Type: DRUG

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

Observation + Deferred Aflibercept

No treatment to start followed by intravitreal aflibercept if vision worsens (deferred laser may be added to intravitreal aflibercept if certain criteria are met)

Group Type: ACTIVE_COMPARATOR

Deferred laser

Intervention Type: PROCEDURE

Focal/grid laser is initiated while receiving anti-VEGF injections only if certain criteria are met

Deferred aflibercept

Intervention Type: DRUG

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

Prompt Aflibercept

Intravitreal aflibercept at baseline and every 4 weeks as needed (deferred laser may be added to intravitreal aflibercept if certain criteria are met)

Group Type: EXPERIMENTAL

Prompt aflibercept

Intervention Type: DRUG

Intravitreal injection of 2.0mg aflibercept performed on the day of randomization and up to every 4 weeks using defined treatment criteria

Deferred laser

Intervention Type: PROCEDURE

Focal/grid laser is initiated while receiving anti-VEGF injections only if certain criteria are met

Interventions

Prompt Laser

Focal/grid laser performed at baseline and as needed during follow-up

Intervention Type: PROCEDURE

Prompt aflibercept

Intravitreal injection of 2.0mg aflibercept performed on the day of randomization and up to every 4 weeks using defined treatment criteria

Intervention Type: DRUG

Deferred laser

Focal/grid laser is initiated while receiving anti-VEGF injections only if certain criteria are met

Intervention Type: PROCEDURE

Deferred aflibercept

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

Intervention Type: DRUG

Other Intervention Names

focal/grid photocoagulation; laser treatment; intravitreal anti-VEGF; Eylea; focal/grid photocoagulation; laser treatment; intravitreal anti-VEGF; Eylea

Eligibility Criteria

Inclusion Criteria

1. Age >= 18 years

2. 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:

1. Current regular use of insulin for the treatment of diabetes

2. Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes

3. Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria.

3. Able and willing to provide informed consent.

Meets all of the following ocular criteria in at least the one eye:

1. 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.

2. On clinical exam, definite retinal thickening due to DME involving the center of the macula.

3. 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.

4. 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.

5. Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCT and fundus photographs.

Exclusion Criteria

1. History of chronic renal failure requiring dialysis or kidney transplant.

2. 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).

3. 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.

4. 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.

5. Known allergy to any component of the study drug.

6. 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.

7. Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

These drugs should not be used during the study.

8. 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.

9. 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:

1. 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.

2. An ocular condition is present such that, in the opinion of the investigator, any visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).

3. An ocular condition is present (other than DME) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).

4. Cataract is present that, in the opinion of the investigator, may alter visual acuity during the course of the study.

5. Any history of prior laser or other surgical, intravitreal, or peribulbar treatment for DME (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, or anti-VEGF).

6. History of topical steroid or nonsteroidal anti-inflammatory drugs (NSAID) treatment within 30 days prior to randomization.

7. History of intravitreal or peribulbar corticosteroid within 4 months prior to randomization for an ocular condition other than DME.

8. Any history of or anticipated need for intravitreal anti-VEGF within the next 6 months for an ocular condition other than DME (e.g. choroidal neovascularization, central retinal vein occlusion, PDR).

9. History of PRP within 4 months prior to randomization or anticipated need for PRP in the 6 months following randomization.

10. Any history of vitrectomy.

11. History of major ocular surgery (cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.

12. History of YAG capsulotomy performed within 2 months prior to randomization.

13. Aphakia.

14. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

National Eye Institute (NEI)

NIH

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carl Baker, MD

Role: STUDY_CHAIR

Paducah Retina Center

Adam Glassman, MS

Role: PRINCIPAL_INVESTIGATOR

Jaeb Center for Health Research

Locations

Arizona Retina and Vitreous Consultants

Phoenix, Arizona, United States

University of Arizona Medical Center/Department of Ophthalmology

Tucson, Arizona, United States

Jones Eye Institute/University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Retinal Diagnostic Center

Campbell, California, United States

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States

South Coast Retina Center

Long Beach, California, United States

Southern California Desert Retina Consultants, MC

Palm Desert, California, United States

Retina Consultants of Southern California

Redlands, California, United States

Retinal Consultants Medical Group, Inc.

Sacramento, California, United States

California Retina Consultants

Santa Barbara, California, United States

Bay Area Retina Associates

Walnut Creek, California, United States

Retinal Consultants of Southern California Medical Group, Inc.

Westlake Village, California, United States

Retina Group of New England

New London, Connecticut, United States

New England Retina Associates

Norwich, Connecticut, United States

National Ophthalmic Research Institute

Fort Myers, Florida, United States

University of Florida College of Med., Department of Ophthalmology

Jacksonville, Florida, United States

Florida Retina Consultants

Lakeland, Florida, United States

Retina Macula Specialists of Miami

Miami, Florida, United States

Bascom Palmer Eye Institute

Miami, Florida, United States

Ocala Eye Retina Consultants

Ocala, Florida, United States

Magruder Eye Institute

Orlando, Florida, United States

Fort Lauderdale Eye Institute

Plantation, Florida, United States

Center for Sight

Sarasota, Florida, United States

Sarasota Retina Institute

Sarasota, Florida, United States

Retina Associates of Florida, P.A.

Tampa, Florida, United States

Emory Eye Center

Atlanta, Georgia, United States

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Marietta Eye Clinic

Marietta, Georgia, United States

Thomas Eye Group

Sandy Springs, Georgia, United States

Northwestern Medical Faculty Foundation

Chicago, Illinois, United States

University of Illinois at Chicago Medical Center

Chicago, Illinois, United States

NorthShore University HealthSystem

Glenview, Illinois, United States

Illinois Retina Associates

Joliet, Illinois, United States

University Retina and Macula Associates

Oak Forest, Illinois, United States

Carle Foundation Hospital

Urbana, Illinois, United States

Raj Maturi

Indianapolis, Indiana, United States

John-Kenyon American Eye Institute

New Albany, Indiana, United States

Medical Associates Clinic, P.C.

Dubuque, Iowa, United States

Wolfe Eye Clinic

West Des Moines, Iowa, United States

University of Kansas Medical Center, Dept. of Ophthalmology

Prairie Village, Kansas, United States

Retina Associates, P.A.

Shawnee Mission, Kansas, United States

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Paducah Retinal Center

Paducah, Kentucky, United States

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Wilmer Eye Institute at Johns Hopkins

Baltimore, Maryland, United States

Joslin Diabetes Center

Boston, Massachusetts, United States

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, United States

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, United States

Henry Ford Health System, Dept of Ophthalmology and Eye Care Services

Detroit, Michigan, United States

Retina Vitreous Center

Grand Blanc, Michigan, United States

Retina Specialists of Michigan

Grand Rapids, Michigan, United States

Vitreo-Retinal Associates

Grand Rapids, Michigan, United States

Andersen Eye Associates

Saginaw, Michigan, United States

Retina Center, PA

Minneapolis, Minnesota, United States

University of Minnesota

Minneapolis, Minnesota, United States

Mayo Clinic Department of Ophthalmology

Rochester, Minnesota, United States

Mid-America Retina Consultants, P.A.

Kansas City, Missouri, United States

The Retina Institute

St Louis, Missouri, United States

Eyesight Ophthalmic Services, PA

Portsmouth, New Hampshire, United States

The Institute of Ophthalmology and Visual Science (IOVS)

Newark, New Jersey, United States

Retinal and Ophthalmic Consultants, PC

Northfield, New Jersey, United States

Eye Associates of New Mexico

Albuquerque, New Mexico, United States

Ross Eye Institute, SUNY Buffalo

Buffalo, New York, United States

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, United States

MaculaCare

New York, New York, United States

Retina Associates of Western New York

Rochester, New York, United States

University of Rochester

Rochester, New York, United States

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

Western Carolina Retinal Associates, PA

Asheville, North Carolina, United States

University of North Carolina

Chapel Hill, North Carolina, United States

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Charlotte, North Carolina, United States

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States

Case Western Reserve University

Cleveland, Ohio, United States

Retina Vitreous Center

Edmond, Oklahoma, United States

Oregon Retina, LLP

Eugene, Oregon, United States

Retina Northwest, PC

Portland, Oregon, United States

Casey Eye Institute

Portland, Oregon, United States

Family Eye Group

Lancaster, Pennsylvania, United States

Retina Vitreous Consultants

Monroeville, Pennsylvania, United States

University of Pennsylvania Scheie Eye Institute

Philadelphia, Pennsylvania, United States

Carolina Retina Center

Columbia, South Carolina, United States

Palmetto Retina Center

West Columbia, South Carolina, United States

Southeastern Retina Associates

Chattanooga, Tennessee, United States

Southeastern Retina Associates, PC

Kingsport, Tennessee, United States

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

Southwest Retina Specialists

Amarillo, Texas, United States

Austin Retina Associates

Austin, Texas, United States

Retina Research Center

Austin, Texas, United States

Retina and Vitreous of Texas

Houston, Texas, United States

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Retina Consultants of Houston, PA

Houston, Texas, United States

Texas Retina Associates

Lubbock, Texas, United States

Valley Retina Institute

McAllen, Texas, United States

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Retina Associates of Utah, P.C.

Salt Lake City, Utah, United States

Retina Institute of Virginia

Richmond, Virginia, United States

Virginia Commonwealth University, Dept. of Ophthalmology

Richmond, Virginia, United States

University of Washington Medical Center

Seattle, Washington, United States

Spokane Eye Clinic

Spokane, Washington, United States

University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service

Madison, Wisconsin, United States

Alberta Retina Consultants

Edmonton, Alberta, Canada

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

UBC/VCHA Eye Care Centre

Vancouver, , Canada

Countries

United States; Canada

References

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.

Reference Type: BACKGROUND

PMID: 32077907 (View on PubMed)

Baker 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.

Reference Type: RESULT

PMID: 31037289 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

EY14231

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EY23207

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

EY18817

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DRCR.net Protocol V

Identifier Type: -

Identifier Source: org_study_id