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Trial record 1 of 1 for:    Protocol V, DRCR
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Treatment for CI-DME in Eyes With Very Good VA Study (Protocol V)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01909791
Recruitment Status : Completed
First Posted : July 29, 2013
Results First Posted : January 3, 2020
Last Update Posted : July 31, 2020
Sponsor:
Collaborators:
Regeneron Pharmaceuticals
National Eye Institute (NEI)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
Jaeb Center for Health Research

Tracking Information
First Submitted Date  ICMJE July 23, 2013
First Posted Date  ICMJE July 29, 2013
Results First Submitted Date  ICMJE September 11, 2019
Results First Posted Date  ICMJE January 3, 2020
Last Update Posted Date July 31, 2020
Study Start Date  ICMJE October 2013
Actual Primary Completion Date September 11, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 16, 2019)
Number of Eyes With at Least 5-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline [ Time Frame: 2 years ]
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).
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2013)
Percent of eyes that have lost at least 5 letters of visual acuity at 2 years compared with baseline mean visual acuity [ Time Frame: 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 16, 2019)
  • 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 [ Time Frame: 1 year ]
    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).
  • Change in E-ETDRS Visual Acuity Letter Score From Baseline [ Time Frame: 1 year ]
    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).
  • Change in E-ETDRS Visual Acuity Letter Score From Baseline Over 2 Years (Area Under the Curve) [ Time Frame: 2 year ]
    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). The area under the curve (units = letters·years) was divided by 2 years (units = years) to obtain an average change in letter score (units = letters) over the 2-year follow-up.
  • Change in OCT Central Subfield Thickness From Baseline [ Time Frame: 2 years ]
  • Number of Eyes With at Least 1 or 2 Logarithmic-step Central Subfield Thickness Improvement and Worsening [ Time Frame: 1 year ]
    Logarithmic transformation of optical coherence tomography central subfield thickness (CST) is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.
  • Number of Eyes With no Center-involved Diabetic Macular Edema and at Least 10% Central Subfield Thickness Decrease [ Time Frame: 1 year ]
    Center-involved diabetic macular edema defined as follows by central subfield thickness according to optical coherence tomography machine and sex: Heidelberg Spectralis ≥ 305 µm in women and ≥ 320 µm in men, and Zeiss Cirrus ≥ 290 µm in women and ≥ 305 µm in men.
  • Cumulative Number of Intraocular Injections of 2.0-mg Aflibercept Received Per Participant [ Time Frame: 1 year ]
  • Number of Eyes With ≥ 2-step Worsening of Diabetic Retinopathy [ Time Frame: 2 years ]
    Includes eyes with baseline severity level of 75 (high-risk proliferative diabetic retinopathy) or less based on reading center grading of color fundus photographs using the Early Treatment Diabetic Retinopathy Study severity scale.
  • For Eyes Randomized to Initial Laser Photocoagulation and Initial Observation Groups, the Percentage Receiving Aflibercept Treatment [ Time Frame: 2 years ]
  • Number of Eyes With at Least 5-, 10-, or 15-letter Decrease in E-ETDRS Visual Acuity Letter Score From Baseline [ Time Frame: 2 years ]
    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).
  • Change in E-ETDRS Visual Acuity Letter Score From Baseline [ Time Frame: 2 years ]
    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).
  • Change in OCT Central Subfield Thickness From Baseline [ Time Frame: 1 year ]
    Measured using spectral-domain optical coherence tomography (OCT).
  • Number of Eyes With at Least 1 or 2 Logarithmic-step Central Subfield Thickness Improvement and Worsening [ Time Frame: 2 years ]
    Logarithmic transformation of optical coherence tomography central subfield thickness is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.
  • Number of Eyes With no Center-involved Diabetic Macular Edema and at Least 10% Central Subfield Thickness Decrease [ Time Frame: 2 years ]
    Center-involved diabetic macular edema defined as follows by central subfield thickness according to optical coherence tomography machine and sex: Heidelberg Spectralis ≥ 305 µm in women and ≥ 320 µm in men, and Zeiss Cirrus ≥ 290 µm in women and ≥ 305 µm in men.
  • Cumulative Number of Focal/Grid Photocoagulation Sessions Performed Per Participant [ Time Frame: 2 years ]
  • Number of Eyes With ≥ 2-step Improvement of Diabetic Retinopathy [ Time Frame: 2 years ]
    Includes eyes with baseline severity level of 35 (mild non-proliferative diabetic retinopathy) or greater based on reading center grading of color fundus photographs using the Early Treatment Diabetic Retinopathy Study severity scale. Excludes eyes with severity level 60 at baseline since improvement is not possible in these eyes.
  • Cumulative Number of Intraocular Injections of 2.0-mg Aflibercept Received Per Participant [ Time Frame: 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2013)
  • Percent of eyes with at least 5, 10 and 15 letter losses in visual acuity from baseline mean visual acuity [ Time Frame: 1 & 2 years ]
  • Percent of eyes with at least 5 letter gain in visual acuity from baseline mean visual acuity [ Time Frame: 1 & 2 years ]
  • Mean change in visual acuity, adjusted for baseline mean visual acuity [ Time Frame: 1 & 2 years ]
  • Visual acuity area under the curve between baseline and annual visits [ Time Frame: 1 & 2 years ]
  • Mean change in OCT CSF thickness, adjusted for baseline mean thickness [ Time Frame: 1 & 2 years ]
  • Percent of eyes with at least a 1 and 2 log step increase or decrease on OCT CSF thickness [ Time Frame: 1 & 2 years ]
  • Percent of eyes with OCT CSF thickness of <250 µm on Stratus OCT (or spectral domain equivalent) and at least a 10% OCT CSF thickness decrease [ Time Frame: 1 & 2 years ]
  • Number of injections and/or focal/grid photocoagulation sessions performed [ Time Frame: 1 & 2 years ]
  • Number of scheduled and unscheduled visits [ Time Frame: 1 & 2 years ]
  • Percent of eyes with worsening diabetic retinopathy [ Time Frame: 1 & 2 years ]
  • Of eyes with non-proliferative diabetic retinopathy or proliferative diabetic retinopathy (PDR) at randomization, percent with improvement in diabetic retinopathy [ Time Frame: 1 & 2 years ]
  • Of eyes with PDR at randomization, proportion of eyes avoiding vitreous hemorrhage or panretinal photocoagulation (PRP) or vitrectomy for PDR [ Time Frame: 1 & 2 years ]
  • Mean change in low-contrast visual acuity on Electronic Visual Acuity Tester [ Time Frame: 1 & 2 years ]
  • Total cost of follow-up and treatment [ Time Frame: 1 & 2 years ]
  • For eyes randomized to deferred anti-VEGF, the percentage of eyes needing anti-VEGF treatment. [ Time Frame: 1 & 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment for CI-DME in Eyes With Very Good VA Study
Official Title  ICMJE Treatment for Central-Involved Diabetic Macular Edema in Eyes With Very Good Visual Acuity
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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Diabetic Macular Edema
Intervention  ICMJE
  • Procedure: Prompt Laser
    Focal/grid laser performed at baseline and as needed during follow-up
    Other Names:
    • focal/grid photocoagulation
    • laser treatment
  • Drug: Prompt aflibercept
    Intravitreal injection of 2.0mg aflibercept performed on the day of randomization and up to every 4 weeks using defined treatment criteria
    Other Names:
    • intravitreal anti-VEGF
    • Eylea
  • Procedure: Deferred laser
    Focal/grid laser is initiated while receiving anti-VEGF injections only if certain criteria are met
    Other Names:
    • focal/grid photocoagulation
    • laser treatment
  • Drug: 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
    Other Names:
    • intravitreal anti-VEGF
    • Eylea
Study Arms  ICMJE
  • Experimental: Prompt Laser + Deferred Aflibercept
    Focal/grid laser followed by intravitreal aflibercept if vision worsens
    Interventions:
    • Procedure: Prompt Laser
    • Drug: Deferred aflibercept
  • Active Comparator: 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)
    Interventions:
    • Procedure: Deferred laser
    • Drug: Deferred aflibercept
  • Experimental: 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)
    Interventions:
    • Drug: Prompt aflibercept
    • Procedure: Deferred laser
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 26, 2013)
702
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 11, 2018
Actual Primary Completion Date September 11, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01909791
Other Study ID Numbers  ICMJE DRCR.net Protocol V
EY14231 ( Other Grant/Funding Number: National Eye Institute )
EY23207 ( Other Grant/Funding Number: National Eye Institute )
EY18817 ( Other Grant/Funding Number: National Eye Institute )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jaeb Center for Health Research
Study Sponsor  ICMJE Jaeb Center for Health Research
Collaborators  ICMJE
  • Regeneron Pharmaceuticals
  • National Eye Institute (NEI)
  • National Institutes of Health (NIH)
Investigators  ICMJE
Study Chair: Carl Baker, MD Paducah Retina Center
Principal Investigator: Adam Glassman, MS Jaeb Center for Health Research
PRS Account Jaeb Center for Health Research
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP