Prompt Panretinal Photocoagulation Versus Ranibizumab+Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy (Protocol S)

October 27, 2021 updated by: Jaeb Center for Health Research

Prompt Panretinal Photocoagulation Versus Intravitreal Ranibizumab With Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

The primary objective of the protocol is to determine if visual acuity outcomes at 2 years in eyes with proliferative diabetic retinopathy (PDR) that receive anti-vascular endothelial growth factor (anti-VEGF) therapy with deferred panretinal photocoagulation (PRP) are non-inferior to those in eyes that receive standard prompt PRP therapy.

Secondary objectives include:

  • Comparing other visual function outcomes (including Humphrey visual field testing and study participant self-reports of visual function) in eyes receiving anti-VEGF with deferred PRP with those in eyes receiving prompt PRP.
  • Determining percent of eyes not requiring PRP when anti-VEGF is given in the absence of prompt PRP.
  • Comparing safety outcomes between treatment groups.
  • Comparing associated treatment and follow-up exam costs between treatment groups.

Study Overview

Study Type

Interventional

Enrollment (Actual)

305

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Arizona
      • Phoenix, Arizona, United States, 85014
        • Retinal Consultants of AZ
    • California
      • Loma Linda, California, United States, 92354
        • Loma Linda University Health Care, Dept. of Ophthalmology
      • Palm Springs, California, United States, 92262
        • Southern California Desert Retina Consultants, MC
      • Santa Barbara, California, United States, 93103
        • California Retina Consultants
      • Walnut Creek, California, United States, 94598
        • Bay Area Retina Associates
    • Connecticut
      • Trumbull, Connecticut, United States, 06611
        • New England Retina Associates
    • Florida
      • Fort Myers, Florida, United States, 33912
        • Retina Consultants of Southwest Florida
      • Lakeland, Florida, United States, 33805
        • Central Florida Retina Institute
      • Ocala, Florida, United States, 34474
        • Ocala Eye Retina Consultants
      • Plantation, Florida, United States, 33324
        • Fort Lauderdale Eye Institute
      • Venice, Florida, United States, 34285
        • Retina Associates of Sarasota
    • Georgia
      • Augusta, Georgia, United States, 30909
        • Southeast Retina Center, P.C.
    • Illinois
      • Glenview, Illinois, United States, 60026
        • North Shore University Health System
    • Indiana
      • Indianapolis, Indiana, United States, 46290
        • Raj K. Maturi, M.D., P.C.
      • New Albany, Indiana, United States, 47150
        • John-Kenyon American Eye Institute
    • Iowa
      • West Des Moines, Iowa, United States, 50266
        • Wolfe Eye Clinic
    • Kentucky
      • Lexington, Kentucky, United States, 40509-1802
        • Retina and Vitreous Associates of Kentucky
      • Paducah, Kentucky, United States, 42001
        • Paducah Retinal Center
    • Maryland
      • Baltimore, Maryland, United States, 21237
        • Elman Retina Group, P.A.
    • Massachusetts
      • Worcester, Massachusetts, United States, 01605
        • Vitreo-Retinal Associates, PC
    • Michigan
      • Grand Blanc, Michigan, United States, 48439
        • Retina Vitrous Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Barnes Retina Institute
    • Nebraska
      • Lincoln, Nebraska, United States, 38506
        • Eye Surgical Associates
    • New York
      • New York, New York, United States, 10003
        • The New York Eye and Ear Infirmary/Faculty Eye Practice
      • Rochester, New York, United States, 14642
        • University of Rochester
      • Syracuse, New York, United States, 13224
        • Retina-Vitreous Surgeons of Central New York, PC
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7040
        • University of North Carolina
      • Charlotte, North Carolina, United States, 28210
        • Charlotte Eye, Ear, Nose and Throat Assoc., PA
    • Ohio
      • Beachwood, Ohio, United States, 44122
        • Retina Associates of Cleveland, Inc.
    • Oregon
      • Portland, Oregon, United States, 97239
        • Casey Eye Institute
      • Portland, Oregon, United States, 97210
        • Retina Northwest, PC
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State College of Medicine
      • Lancaster, Pennsylvania, United States, 17601-2644
        • Family Eye Group
      • Pittsburgh, Pennsylvania, United States, 15213
        • Retina Vitrous Consultants
    • South Carolina
      • Columbia, South Carolina, United States, 29223
        • Carolina Retina Center
    • Tennessee
      • Kingsport, Tennessee, United States, 37660
        • Southeastern Retina Associates, PC
      • Knoxville, Tennessee, United States, 37909
        • Southeastern Retina Associates, P.C.
    • Texas
      • Austin, Texas, United States, 78705
        • Austin Retina Associates
      • Austin, Texas, United States, 78705
        • Retina Research Center
      • Dallas, Texas, United States, 75231
        • Texas Retina Associates
      • Houston, Texas, United States, 77025
        • Retina and Vitreous of Texas
      • Houston, Texas, United States, 77030
        • Baylor Eye Physicians and Surgeons
      • Lubbock, Texas, United States, 79424
        • Texas Retina Associates
      • McAllen, Texas, United States, 78503
        • Valley Retina Institute
      • San Antonio, Texas, United States, 78240
        • Retinal Consultants of San Antonio
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Medical Center
      • Spokane, Washington, United States, 99204
        • Spokane Eye Clinic
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wiconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Age >= 18 years -Individuals < 18 years old are not being included because proliferative diabetic retinopathy (PDR) is so rare in this age group that the diagnosis of PDR 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 American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria (see Procedures Manual for definitions) Able and willing to provide informed consent.

Meets at least all of the following ocular criteria criteria:

  • Presence of PDR which the investigator intends to manage with PRP alone but for which PRP can be deferred for at least 4 weeks in the setting of intravitreal ranibizumab, in the investigator's judgment.
  • Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity letter score > 24 (approximate Snellen equivalent 20/320) on the day of randomization.
  • Media clarity, pupillary dilation, and study participant cooperation sufficient to administer PRP and obtain adequate fundus photographs and optical coherence tomography (OCT).

    • Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality

Exclusion Criteria:

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 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 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.

  • Study participants cannot receive another investigational drug while participating in the study.

Known allergy to any component of the study drug.

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.

Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

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 3 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 (DRCR.net) certified clinical center during the 3 years of the study.

Individual has any of the following ocular characteristics:

  • History of prior panretinal photocoagulation (prior PRP is defined as ≥ 100 burns outside of the posterior pole)
  • Tractional retinal detachment involving the macula.

    -- A tractional retinal detachment is not an exclusion if it is outside of the posterior pole (not threatening the macula) and in the investigator's judgment, is not a contraindication to intravitreal ranibizumab treatment and also does not preclude deferring PRP for at least 4 weeks in the setting of intravitreal ranibizumab

  • Exam evidence of neovascularization of the angle (neovascularization of the iris alone is not an exclusion if it does not preclude deferring PRP for at least 4 weeks in the investigator's judgment).
  • If macular edema is present, it is considered to be primarily due to a cause other than diabetic macular edema.

    -- An eye should not be considered eligible if:

    • macular edema is present that is considered to be related to ocular surgery such as cataract extraction or
    • clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of any macular edema.
  • An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).

    -- A vitreous or preretinal hemorrhage is not an exclusion if it is out of the visual axis and in the investigator's judgment is not having any affect on visual acuity.

  • Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye were otherwise normal).
  • History of intravitreal anti-VEGF treatment at any time in the past 2 months.
  • History of corticosteroid treatment (intravitreal or peribulbar) at any time in the past 4 months.

    --If the investigator believes that there may still be a substantial effect 4 months after prior treatment (e.g., dose of intravitreal triamcinolone higher than 4 mg), the eye should not be included.

  • History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
  • History of (yttrium-aluminum-garnet) YAG capsulotomy performed within 2 months prior to randomization.
  • Aphakia.
  • Uncontrolled glaucoma (in investigator's judgment).
  • Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Anti-VEGF+Deferred PRP
Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.
PRP is deferred until failure/futility criteria for intravitreal injection are met.
ACTIVE_COMPARATOR: Prompt PRP
PRP= Panretinal Photocoagulation. PRP alone.
Panretinal photocoagulation alone at baseline (full session completed within 56 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Change in Visual Acuity From Baseline
Time Frame: 2-years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean Visual Acuity
Time Frame: 2-years
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
Number of Eyes With Greater Than or Equal to 10 Letter Vision Gain
Time Frame: 2-years
2-years
Humphrey Visual Field Test Cumulative Score Change From Baseline
Time Frame: 2-years
Visual fields, collected using the Humphrey Visual Field analyzer, measured the total point score (sum of retinal sensitivities of all points) tested on 30-2 and 60-4 patterns, which included the mid-peripheral and peripheral visual fields. A lower score indicates greater visual field loss.The cumulative score is the sum of all visual field sensitivity values for each of the four individual quadrants of the visual field (the quadrants are divided by the horizontal and vertical lines). The range can be from 0 to about 600 for the 30-2 test [for each quadrant], and from 0 to about 400 or 450 for the peripheral test.
2-years
Frequency of Vitrectomy
Time Frame: 2-years
2-years
Mean Change in OCT Central Subfield Thickness From Baseline
Time Frame: 2-years
All baseline and 2-year optical coherence tomography (OCT) scans were evaluated by the OCT reading center.
2-years
Development of Central DME With Vision Impairment by 2-years
Time Frame: 2-years
2-years
Number of Eyes With Vitreous Hemorrhage
Time Frame: 2-years
2-years
Number of Eyes Without Active or Regressed Neovascularization on Fundus Photography at 2-years
Time Frame: 2-years
2-years
Number of Eyes With Greater Than or Equal to 10 Letter Vision Loss
Time Frame: 2-year
2-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Chair: Jeffrey G Gross, MD, Carolina Retina Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2012

Primary Completion (ACTUAL)

January 1, 2015

Study Completion (ACTUAL)

February 5, 2018

Study Registration Dates

First Submitted

December 6, 2011

First Submitted That Met QC Criteria

December 7, 2011

First Posted (ESTIMATE)

December 9, 2011

Study Record Updates

Last Update Posted (ACTUAL)

October 29, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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