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Diabetic Macular EdemaPhase 2NCT01945866

Phase II Combination Steroid and Anti-VEGF for Persistent DME

A Phase 2 study testing intravitreal ranibizumab 0.3 mg and dexamethasone intravitreal implant in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 56 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

Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as treatment for center-involved diabetic macular edema (DME), a substantial proportion of anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of retinal thickening. 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?
intravitreal ranibizumab 0.3 mg and dexamethasone intravitreal implant
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
129 participants
Where
56 sitesUnited States
Study dates
Feb 2014to 5 Jun 2017
Phase
Phase 2
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

  • Age ≥ 18 years i) Individuals <18 years old are not being included because DME is so rare in this age group that the diagnosis of DME may be questionable.
  • 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 ADA (American Diabetes Association) and/or WHO (World Health Organization) criteria
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  • At least one eye meets the study eye criteria listed below.
  • Fellow eye (if not a study eye) meets criteria.
  • Able and willing to provide informed consent.
  • Meets all of the following ocular criteria in at least the one eye:
  • At least 3 injections of anti-VEGF drug (ranibizumab, bevacizumab, or aflibercept) within the prior 20 weeks.
  • Visual acuity letter score in study eye ≤ 78 and ≥24 (approximate Snellen equivalent 20/32 to 20/320).
  • On clinical exam, definite retinal thickening due to DME involving the center of the macula.
  • OCT CSF thickness, within 8 days of enrollment:
  • On Zeiss Cirrus ≥ 290 microns in women; ≥ 305 in men ii) On Heidelberg Spectralis: ≥ 305 microns in women; ≥ 320 in men
  • Media clarity, pupillary dilation, and individual cooperation sufficient for adequate OCTs.

Who cannot join

  • An individual is not eligible if any of the following exclusion criteria are present:
  • 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 enrollment that involved treatment with any drug that has not received regulatory approval for the indication being studied. Note: study participants cannot receive another investigational drug while participating in the study.
  • Known allergy to any component of the study drugs (including povidone iodine prep).
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  • Blood pressure > 180/110 (systolic above 180 OR diastolic above 110). If blood pressure is brought below 180/110 by anti-hypertensive treatment, the individual can become eligible.
  • Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 1 month prior to enrollment.
  • Systemic steroid, anti-VEGF or pro-VEGF treatment within 4 months prior to enrollment 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 9 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 9 months.
  • The following exclusions apply to the study eye only (i.e., they may be present for the non-study eye unless otherwise specified):
  • Macular edema is considered to be due to a cause other than DME. 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, non-retinal condition, etc.).
  • 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.).
  • Substantial posterior capsule opacity that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., opacity would be reducing acuity to 20/40 or worse if eye was otherwise normal).
  • History of intravitreal anti-VEGF drug within 21 days prior to enrollment.
  • History of intravitreal or peribulbar corticosteroids within 3 months prior to enrollment.
  • History of macular laser photocoagulation within 4 months prior to enrollment.
  • History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to enrollment or anticipated need for PRP in the 6 months following enrollment into run-in phase.
  • Any history of vitrectomy.

Trial locations and contacts

56 sites in 1 country.

56 sites in 1 country

United States56 sites

  • Southwest Retina Specialists

    Amarillo, Texas, 79106

  • Southeast Retina Center, P.C.

    Augusta, Georgia, 30909

  • Austin Retina Associates

    Austin, Texas, 78705

  • Retina Research Center

    Austin, Texas, 78705

  • Elman Retina Group, P.A.

    Baltimore, Maryland, 21237

  • Retina Associates of Cleveland, Inc.

    Beachwood, Ohio, 44122

  • National Eye Institute/National Institutes of Health

    Bethesda, Maryland, 20892-2510

  • Retina-Vitreous Associates Medical Group

    Beverly Hills, California, 90211

  • Ophthalmic Consultants of Boston

    Boston, Massachusetts, 02114

  • Joslin Diabetes Center

    Boston, Massachusetts, 02215

  • Charlotte Eye Ear Nose and Throat Assoc, PA

    Charlotte, North Carolina, 28210

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Medical Associates Clinic, P.C.

    Dubuque, Iowa, 52002

  • National Ophthalmic Research Institute

    Fort Myers, Florida, 33912

  • Retina Vitreous Center

    Grand Blanc, Michigan, 48439

  • Retina Specialists of Michigan

    Grand Rapids, Michigan, 49525

  • Retina and Vitreous of Texas

    Houston, Texas, 77025

  • Baylor Eye Physicians and Surgeons

    Houston, Texas, 77030

  • Retina Consultants of Houston, PA

    Houston, Texas, 77030

  • Atlantis Eye Care

    Huntington Beach, California, 92647

  • Raj K. Maturi, M.D., P.C.

    Indianapolis, Indiana, 46290

  • University of Florida College of Med., Department of Ophthalmology

    Jacksonville, Florida, 32209

  • Southeastern Retina Associates, P.C.

    Knoxville, Tennessee, 37909

  • Central Florida Retina Institute

    Lakeland, Florida, 33805

  • Virginia Retina Center

    Leesburg, Virginia, 20176

  • Loma Linda University Health Care, Dept. of Ophthalmology

    Loma Linda, California, 92354

  • Texas Retina Associates

    Lubbock, Texas, 79424

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

    Madison, Wisconsin, 53705

  • Valley Retina Institute

    McAllen, Texas, 78503

  • Retina Center, PA

    Minneapolis, Minnesota, 55404

  • Northern California Retina Vitreous Associates

    Mountain View, California, 94040

  • Retina Group of New England

    New London, Connecticut, 06320

  • MaculaCare

    New York, New York, 10021

  • The Institute of Ophthalmology and Visual Science (IOVS)

    Newark, New Jersey, 07103

  • New England Retina Associates

    Norwich, Connecticut, 06360

  • Ocala Eye Retina Consultants

    Ocala, Florida, 34474

  • University of Pennsylvania Scheie Eye Institute

    Philadelphia, Pennsylvania, 19104

  • Retina Northwest, PC

    Portland, Oregon, 97210

  • Casey Eye Institute

    Portland, Oregon, 97239

  • Retina Consultants of Southern California

    Redlands, California, 92374

  • Retina Institute of Virginia

    Richmond, Virginia, 23235

  • Retina Associates of Western New York

    Rochester, New York, 14618

  • University of Rochester

    Rochester, New York, 14642

  • Retinal Consultants Medical Group, Inc.

    Sacramento, California, 95841

  • Retina Associates of Utah, P.C.

    Salt Lake City, Utah, 84107

  • Retinal Consultants of San Antonio

    San Antonio, Texas, 78240

  • Thomas Eye Group

    Sandy Springs, Georgia, 30328

  • California Retina Consultants

    Santa Barbara, California, 93103

  • Sarasota Retina Institute

    Sarasota, Florida, 34239

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Retina Associates, P.A.

    Shawnee Mission, Kansas, 66204

  • Spokane Eye Clinic

    Spokane, Washington, 99204

  • The Retina Institute

    St Louis, Missouri, 63128

  • Retina Associates of Florida, P.A.

    Tampa, Florida, 33609

  • Bay Area Retina Associates

    Walnut Creek, California, 94598

  • Wolfe Eye Clinic

    West Des Moines, Iowa, 50266

Other trials in United States

About this study

Official title: Short-term Evaluation of Combination Corticosteroid+Anti-VEGF Treatment for Persistent Central-Involved Diabetic Macular Edema Following Anti-VEGF Therapy

Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as treatment for center-involved diabetic macular edema (DME), a substantial proportion of anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of retinal thickening. Indeed, over 50% of ranibizumab-treated eyes did not achieve a 2 or more line improvement in visual acuity from baseline at 2 years in Protocol I, a previous DRCR.net (Diabetic Retinopathy Clinical Research Network) study. Furthermore, 27% of ranibizumab-treated eyes still had central subfield (CSF) thickness on time-domain optical coherence tomography (OCT) ≥ 300 at 1 year, and more than 40% of ranibizumab-treated eyes did not achieve complete resolution of retinal thickening (< 250 microns) by 2 years. Thus, there is a need for alternative or additional treatments that will improve vision by reducing retinal edema in eyes with persistent DME following previous anti-VEGF therapy. Intravitreal steroid is not as efficacious as ranibizumab in eyes with DME overall, but it has been shown to have a positive effect for DME in some eyes and might add benefit in eyes that are already receiving anti-VEGF.

The main objective of this study is to assess the short-term effects of combination steroid+anti-VEGF therapy on visual acuity and retinal thickness on OCT in comparison with that of continued anti-VEGF therapy alone in eyes with persistent central-involved DME and visual acuity impairment despite previous anti-VEGF treatment. This study will provide important information for the design of a future confirmatory phase III clinical trial on the efficacy of combination steroid and anti-VEGF in eyes with persistent DME and vision impairment following previous anti-VEGF therapy. The primary outcome for efficacy will be the mean change in visual acuity at 24 weeks.

Each study eye is required to complete a 12-week run-in phase. The run-in phase will identify study eyes that truly have persistent DME despite anti-VEGF therapy by requiring an additional 3 injections while also collecting standardized visual acuity and OCT measurements. At the enrollment, 4-week and 8-week visits of the run-in phase, enrolled eyes will receive an intravitreal injection of ranibizumab 3mg. Then at the 12-week run-in visit, if the eye still has persistent DME, it will be randomized to receive either intravitreal sham+intravitreal ranibizumab 0.3 or intravitreal dexamethasone+intravitreal ranibizumab 0.3 injections. The randomized study duration is 24 week, during which a protocol visit takes place every month. The combination injections of sham+ranibizumab or dexamethasone +ranibizumab will be given at the randomization visit (baseline) and at the 12-week visit after randomization. In between, an intravitreal injection of ranibizumab only will be given to study eyes at the 4, 8, 16 and 20 week visits.

Being tested
intravitreal ranibizumab 0.3 mg, dexamethasone intravitreal implant, Sham injection
Keywords
Diabetic Macular Edema, Anti-vascular endothelial growth factor, Dexamethasone Intravitreal implant, Ranibizumab intravitreal injection

What participants receive

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

  • intravitreal ranibizumab 0.3 mgDrug

    Also called Lucentis

    Intravitreal injection of 0.3mg ranibizumab performed on the day of randomization and up to every 4 weeks using defined treatment criteria

  • dexamethasone intravitreal implantDrug

    Also called Ozurdex

    The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first.

  • Sham injectionProcedure or surgery

    No injection is given. It is a sham injection to keep the participant masked. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first.

Study groups in NCT01945866
Study groupRoleWhat they receive
Sham + intravitreal ranibizumab 0.3 mgActive comparatorIntravitreal ranibizumab will be given on the day of randomization. The sham injection will be given within 0-8 days of the ranibizumab injection. If the injections are given consecutively on the same day, the sham injection must be given first. Follow-up intravitreal injections of ranibizumab will be given up to every 4 weeks using defined treatment criteria.
Receives: Drug: intravitreal ranibizumab 0.3 mg; Procedure: Sham injection
Intravitreal dexamethasone+intravitreal ranibizumab 0.3mgExperimentalThe initial intravitreal ranibizumab injection will be given on the day of randomization. The dexamethasone intravitreal injection will be given within 0-8 days of the ranibizumab injection. If defined criteria are met, a second dexamethasone injection in combination with intravitreal ranibizumab (within 0-8 days) will be given at the 12 week visit. If the injections are given consecutively on the same day, the ranibizumab injection must be given first.
Receives: Drug: intravitreal ranibizumab 0.3 mg; Drug: dexamethasone intravitreal implant

What is being measured

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

  1. Mean Change in Visual Acuity Letter Score

    At 24 weeks after randomization, mean change in visual acuity letter score, adjusted for visual acuity at time of randomization

    Measured: 24 weeks after randomization

Secondary outcomes (6)

  1. At 24 Weeks After Randomization, Number of Eyes With at Least 10 and at Least 15 Letter Gain (Increase) or Loss (Decrease) in E-ETDRS Letter Score Visual Acuity.

    ETDRS (Early Treatment Diabetic Retinopathy Study)

    Measured: 24 weeks weeks after randomization

  2. Visual Acuity Area Under the Curve (AUC) Between Randomization and 24 Weeks

    Only included participants who completed the 24-week visit. Time points for which data were collected for this analysis include 0, 4 8,12, 16, 20, and 24 weeks post randomization.

    Measured: 24 weeks after randomization

  3. Mean Change in OCT CSF Thickness, Adjusted for Thickness at Time of Randomization

    Change in optical coherence tomography (OCT) central subfield thickness (in microns) was truncated to 3 standard deviations from the mean [-372, +201] (calculated using observed changes at 24 weeks combining all treatment groups), to minimize the effect of outliers. Two values were truncated in the sham + ranibizumab group: one on the negative end, and one on the positive end.

    Measured: 24 weeks after randomization

  4. Number of Eyes With ≥1 and ≥2 logOCT Step Gain or Loss in CSF Thickness

    Change in optical coherence tomography (OCT) central subfield (CSF) thickness (in microns) was truncated to 3 standard deviations from the mean [-372, +201] (calculated using observed changes at 24 weeks combining all treatment groups), to minimize the effect of outliers. Two values were truncated in the sham + ranibizumab group: one on the negative end, and one on the positive end.

    Measured: 24 weeks after randomization

  5. Eyes With OCT CSF Thickness < the Gender-specific Spectral Domain OCT Equivalent of 250 Microns on Zeiss Stratus

    Gender and OCT machine-specific values for OCT central subfield thickness (in microns) are defined as: <290 in women and <305 in men in Zeiss Cirrus; <305 in women and <320 in men in Heidelberg Spectralis

    Measured: 24 weeks after randomization

  6. OCT CSF Thickness Area Under the Curve Between Randomization and 24 Weeks

    Including participants who completed the 24-week visit. Time points for which data were collected for this analysis include 0, 4 8,12, 16, 20, and 24 weeks post randomization.

    Measured: 24 weeks after randomization

Timeline

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

  1. First posted19 Sep 2013 (estimated)
  2. Study startFeb 2014
  3. Primary completion5 Jun 2017
  4. Study completion5 Jun 2017

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
129 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01945866
Sponsor's protocol ID
DRCR.net Protocol U
Other IDs
EY14231, EY23207, EY18817
Status last verified
Sep 2018
First submitted
12 Sep 2013
Last updated
25 Sep 2018
Data monitoring committee
Yes

Publications

  • Maturi RK, Glassman AR, Liu D, Beck RW, Bhavsar AR, Bressler NM, Jampol LM, Melia M, Punjabi OS, Salehi-Had H, Sun JK; Diabetic Retinopathy Clinical Research Network. Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema: A DRCR Network Phase 2 Randomized Clinical Trial. JAMA Ophthalmol. 2018 Jan 1;136(1):29-38. doi: 10.1001/jamaophthalmol.2017.4914.

    PubMed 29127949

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing intravitreal ranibizumab 0.3 mg and dexamethasone intravitreal implant in people with Diabetic Macular Edema, run by Jaeb Center for Health Research at 56 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 16 inclusion and 21 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 25 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 56 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 Sep 2018). 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 Letter Score (time frame: 24 weeks after randomization). 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 NCT01945866, 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 25 Sep 2018.

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