AzTrials
AzTrials

Diabetic Macular EdemaPhase 3DRCR ACNCT03321513

DRCR.Net Aflibercept vs. Bevacizumab + Deferred Aflibercept for the Treatment of CI-DME

A Phase 3 study testing intravitreous aflibercept and Bevacizumab + Deferred Aflibercept Group in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 54 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Both aflibercept and bevacizumab have been shown to improve vision in eyes with DME. In eyes with DME and at least moderate vision loss, both aflibercept and bevacizumab were also shown to be successful in many eyes. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetic Macular Edema
What is being tested?
intravitreous aflibercept and Bevacizumab + Deferred Aflibercept Group
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
54 sitesUnited States
Study dates
7 Dec 2017to 22 Dec 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score < 69 (i.e., 20/50 or worse) and ≥ 24 (i.e., 20/320 or better) within eight days of randomization.
  • On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
  • Diabetic macular edema present on optical coherence tomography (OCT) within eight days of randomization
  • Zeiss Cirrus central subfield: ≥ 290µm in women or ≥ 305µm in men
  • Heidelberg Spectralis central subfield: ≥ 305µm in women or ≥ 320µm in men
  • Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality
Show all 24Show fewer
  • Media clarity, pupillary dilation, and individual cooperation sufficient for adequate fundus photographs.
  • Exclusions
  • The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):
  • Macular edema is considered to be due to a cause other than diabetic macular edema.
  • 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 the primary cause of the macular edema.
  • An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).
  • An ocular condition is present (other than diabetes) 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.).
  • Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by three lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  • History of an anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) in the past 12 months or history of any other treatment for DME at any time in the past four months (such as focal/grid macular photocoagulation, intravitreous or peribulbar corticosteroids).
  • Enrollment will be limited to a maximum of 25% of the planned sample size with any history of anti-VEGF treatment for DME. Once this number of eyes has been enrolled, any history of anti-VEGF treatment for DME will be an exclusion criterion.
  • History of pan-retinal photocoagulation within four months prior to randomization or anticipated need for pan-retinal photocoagulation in the six months following randomization.
  • History of anti-VEGF treatment for a disease other than DME in the past 12 months.
  • History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior four months or anticipated within the next six months following randomization.
  • History of YAG capsulotomy performed within two months prior to randomization.
  • Aphakia.
  • Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.
  • Evidence of uncontrolled glaucoma. • Intraocular pressure must be <30, with no more than one topical glaucoma medication, and no documented glaucomatous field loss for the eye to be eligible
  • Note, combination therapies are considered more than one medication

Who cannot join

  • An individual is not eligible if any of the following exclusion criteria are present:
  • Significant renal disease, defined as a 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).
  • Individuals in poor glycemic control who, within the last four months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next four months should not be enrolled.
  • 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 at the time of study entry.
  • Note: study participants cannot receive another investigational drug while participating in the study.
Show all 17Show fewer
  • Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine prep).
  • 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 four months prior to randomization or anticipated use during the study.
  • These drugs cannot be used during the study.
  • For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 24 months.
  • 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 next two years.
  • Study Eye Criteria The study participant must have at least one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below.
  • Study participants can have two study eyes only if both eyes are eligible at the time of randomization. For study participants with two eligible eyes, the logistical complexities of the protocol must be considered for each individual prior to randomizing both eyes.
  • The eligibility criteria for a study eye are as follows:

Trial locations and contacts

54 sites in 1 country.

54 sites in 1 country

United States54 sites

  • Eye Associates of New Mexico

    Albuquerque, New Mexico, 87109

  • Western Carolina Clinical Research, LLC

    Asheville, North Carolina, 28803

  • Southeast Retina Center, P.C.

    Augusta, Georgia, 30909

  • Austin Retina Associates

    Austin, Texas, 78705

  • Retina Research Center

    Austin, Texas, 78705

  • Valley Eye Physicians and Surgeons

    Ayer, Massachusetts, 01432

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • Retinal Diagnostic Center

    Campbell, California, 95008

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

    Charlotte, North Carolina, 28210

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio, 44106

  • National Ophthalmic Research Institute

    Fort Myers, Florida, 33912

  • Macula & Retina Institute

    Glendale, California, 91203

  • Retina Specialists of Michigan

    Grand Rapids, Michigan, 49546

  • Vitreo-Retinal Associates

    Grand Rapids, Michigan, 49546

  • Retina Center of Texas

    Grapevine, Texas, 76051

  • Mid Atlantic Retina Specialists

    Hagerstown, Maryland, 21740

  • Baylor Eye Physicians and Surgeons

    Houston, Texas, 77030

  • Retina Consultants of Houston, PA

    Houston, Texas, 77030

  • Raj K. Maturi, M.D., P.C.

    Indianapolis, Indiana, 46290

  • Florida Retina Institute-Jacksonville

    Jacksonville, Florida, 32216

  • Southeastern Retina Associates, P.C.

    Knoxville, Tennessee, 37909

  • Florida Retina Consultants

    Lakeland, Florida, 33805

  • Loma Linda University Health Care, Department of Ophthalmology

    Loma Linda, California, 92354

  • Texas Retina Associates

    Lubbock, Texas, 79424

  • Valley Retina Institute

    McAllen, Texas, 78503

  • Retina Macula Specialists of Miami

    Miami, Florida, 33126

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Retina Vitreous Consultants

    Monroeville, Pennsylvania, 15146

  • John-Kenyon American Eye Institute

    New Albany, Indiana, 47150

  • MaculaCare

    New York, New York, 10021

  • Illinois Retina Associates, S.C.

    Oak Park, Illinois, 60304

  • East Bay Retina Consultants, Inc

    Oakland, California, 94609-3028

  • Dean A. McGee Eye Institute

    Oklahoma City, Oklahoma, 73104

  • Central Florida Retina

    Orlando, Florida, 32806

  • Florida Retina Institute

    Orlando, Florida, 32806

  • Mid-America Retina Consultants, P.A.

    Overland Park, Kansas, 66211

  • Paducah Retinal Center

    Paducah, Kentucky, 42001

  • Retinavitreous Associates, dba; Mid Atlantic Retina

    Philadelphia, Pennsylvania, 19107-5109

  • Southeast Eye Institute, P.A. dba Eye Associates of Pinellas

    Pinellas Park, Florida, 33782

  • Fort Lauderdale Eye Institute

    Plantation, Florida, 33324

  • Retina Northwest, PC

    Portland, Oregon, 97221

  • Retina Associates of Western New York

    Rochester, New York, 14620

  • Retinal Consultants of San Antonio

    San Antonio, Texas, 78240

  • Thomas Eye Group

    Sandy Springs, Georgia, 30328

  • Retina Associates of Sarasota

    Sarasota, Florida, 34233

  • Sarasota Retina Institute

    Sarasota, Florida, 34239

  • Retina Associates, P.A.

    Shawnee Mission, Kansas, 66204

  • Spokane Eye Clinic

    Spokane, Washington, 99204

  • Springfield Clinic, LLP

    Springfield, Illinois, 62703

  • Cascade Medical Research Institute, LLC

    Springfield, Oregon, 97477

  • The Retina Institute

    St Louis, Missouri, 63128

  • Retina Associates of Florida, LLC

    Tampa, Florida, 33609

  • Retina Specialists of Tampa

    Wesley Chapel, Florida, 33544

  • Eye Associates of Northeast Louisiana dba Haik Humble Eye Center

    West Monroe, Louisiana, 71291

Other trials in United States

About this study

Official title: Randomized Trial of Intravitreous Aflibercept Versus Intravitreous Bevacizumab + Deferred Aflibercept for Treatment of Central-Involved Diabetic Macular Edema

Both aflibercept and bevacizumab have been shown to improve vision in eyes with DME. In eyes with DME and at least moderate vision loss, both aflibercept and bevacizumab were also shown to be successful in many eyes. However, aflibercept was shown to be more effective at improving vision, on average, at 1 year and at 2 years. Due to the large cost difference between the two drugs, many clinicians and patients are choosing to initiate treatment with bevacizumab and then switch to aflibercept depending on the eye's response to bevacizumab treatment. However, there is no scientific evidence that this treatment strategy is as effective at improving vision as initiating treatment with aflibercept. Patients and clinicians do not know if this approach ultimately has deleterious effects on visual acuity. If starting with aflibercept is not better than starting with bevacizumab and switching to aflibercept if needed, the potential cost savings to future patients and the health care system would be substantial. However, if starting with aflibercept is better, then patients, clinicians, and health care providers can make informed decisions for how to best treat patients with DME and at least moderate vision loss.

Study Objectives To compare the efficacy of intravitreous aflibercept with intravitreous bevacizumab + deferred aflibercept if needed in eyes with CI DME and moderate vision loss

Being tested
intravitreous aflibercept, Bevacizumab + Deferred Aflibercept Group
Keywords
Diabetic Macular Edema, anti-vascular endothelial growth factor

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • intravitreous afliberceptDrug

    Also called Eylea

    Intravitreous aflibercept injection is made by Regeneron Pharmaceuticals, Inc. and is approved by the FDA for the treatment of neovascular age-related macular degeneration, macular edema due to central retinal vein occlusion, macular edema due to branch retinal vein occlusion, diabetic macular edema, and diabetic retinopathy in eyes with diabetic macular edema.

    Study eyes assigned to receive aflibercept will receive a dose of 2.0 mg in 0.05 cc. Aflibercept will be obtained commercially by the clinical site. The physical, chemical, and pharmaceutical properties and formulation of aflibercept are provided in the Package Insert.

    Intravitreous Injection Technique The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used.

    The injection will be performed using sterile technique

  • Bevacizumab + Deferred Aflibercept GroupDrug

    Also called Avastin

    Bevacizumab is made by Genentech, Inc. and is approved by the FDA for the treatment of metastatic colorectal cancer as well as the treatment of non-squamous non-small cell lung cancer, glioblastoma, and metastatic renal cell carcinoma.

    Study eyes assigned to receive bevacizumab will receive a dose of 1.25 mg provided by a single compounding pharmacy identified by the Network and distributed by the Network. The volume of the injections will be 0.05 cc.

    Intravitreous injection technique: The injection is preceded by a povidone iodine prep of the conjunctiva. In general, topical antibiotics in the pre-, peri-, or post-injection period should not be used.

    The injection will be performed using a sterile technique.

Study groups in NCT03321513
Study groupRoleWhat they receive
Aflibercept GroupActive comparator2.0 mg intravitreous aflibercept
Receives: Drug: intravitreous aflibercept
Bevacizumab + Deferred Aflibercept GroupExperimental1.25 mg intravitreous bevacizumab + deferred intravitreous 2.0 mg aflibercept if eye meets switch criteria
Receives: Drug: intravitreous aflibercept; Drug: Bevacizumab + Deferred Aflibercept Group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change in Visual Acuity

    Area under the curve mean change in the electronic early treatment diabetic retinopathy study visual acuity. Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, <20/800), with higher scores indicating better vision. The data presented are the best-corrected visual acuity in the study eye after protocol-defined refraction. The primary outcome was the time-averaged change in the visual-acuity letter score over a period of 104 weeks. The score was derived by calculating the area under the curve (AUC) over the 104-week period for the change in visual acuity from baseline and dividing by the length of follow-up.

    Measured: 2 years

Secondary outcomes (12)

  1. Change in Visual Acuity From Baseline

    Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, <20/800), with higher scores indicating better vision.

    Measured: 2 years

  2. Increase in E-ETDRS Visual Acuity Letter Score

    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, 20/10) to 0 letters (Snellen equivalent, <20/800), with higher scores indicating better vision.

    Measured: 2 years

  3. Decrease in E-ETDRS Visual Acuity Letter Score

    Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, <20/800), with higher scores indicating better vision.

    Measured: 2 years

  4. Visual Acuity

    Visual acuity was measured with the Electronic Early Treatment Diabetic Retinopathy Study visual-acuity test on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent, <20/800), with higher scores indicating better vision.

    Measured: 2 years

  5. Optical Coherence Tomography Central Subfield Thickness Change From Baseline

    Measurements made on the Cirrus device were converted to equivalent scores as would be assessed on the Spectralis device with the use of the following formula: Spectralis score = 40.78 + 0.95 × Cirrus score.

    Measured: 2 years

  6. Optical Coherence Tomography Central Subfield Thickness Below the Sex-specific Threshold for Central-involved Diabetic Macular Edema

    Optical coherence tomography (OCT) central subfield thickness equivalents for measurements obtained on Spectral domain OCT machines were 320 μm for men and 305 μm for women on the Spectralis device (Heidelberg) and were 305 μm and 290 μm, respectively on the Cirrus OCT measurement device (Zeiss).

    Measured: 2 years

  7. Number of Visits

    Measured: 2 years

  8. Number of Injections

    All study injections were counted, including aflibercept injections received among eyes in the bevacizumab first group.

    Measured: 2 years

  9. Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria

    Measured: Baseline to 12 weeks

  10. Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria

    Measured: Baseline to 24 weeks

  11. Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria

    Measured: Baseline to 52 weeks

  12. Number of Eyes in the Bevacizumab-first Group Meeting the Switching Criteria

    Measured: Baseline to 104 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2017
  2. Study start7 Dec 2017
  3. Primary completion22 Dec 2021
  4. Study completion22 Dec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
270 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03321513
Sponsor's protocol ID
DRCR.net Protocol AC
Acronym
DRCR AC
Status last verified
Sep 2026
First submitted
23 Oct 2017
Last updated
1 Oct 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jhaveri CD, Glassman AR, Ferris FL 3rd, Liu D, Maguire MG, Allen JB, Baker CW, Browning D, Cunningham MA, Friedman SM, Jampol LM, Marcus DM, Martin DF, Preston CM, Stockdale CR, Sun JK; DRCR Retina Network. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. N Engl J Med. 2022 Aug 25;387(8):692-703. doi: 10.1056/NEJMoa2204225. Epub 2022 Jul 14.

    PubMed 35833805

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing intravitreous aflibercept and Bevacizumab + Deferred Aflibercept Group in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 54 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in Visual Acuity (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03321513, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in