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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Eye Institute (NEI)
Genentech, Inc.
Information provided by (Responsible Party):
Jaeb Center for Health Research
ClinicalTrials.gov Identifier:
NCT01489189
First received: December 6, 2011
Last updated: August 25, 2016
Last verified: August 2016
  Purpose

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.

Condition Intervention Phase
Proliferative Diabetic Retinopathy
Other: Prompt Panretinal Photocoagulation
Drug: 0.5-mg Ranibizumab
Other: Deferred panretinal photocoagulation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prompt Panretinal Photocoagulation Versus Intravitreal Ranibizumab With Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Resource links provided by NLM:


Further study details as provided by Jaeb Center for Health Research:

Primary Outcome Measures:
  • Mean Change in Visual Acuity From Baseline [ Time Frame: 2-years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Mean Visual Acuity [ Time Frame: 2-years ] [ Designated as safety issue: No ]
    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.

  • Number of Eyes With Greater Than or Equal to 10 Letter Vision Gain [ Time Frame: 2-years ] [ Designated as safety issue: No ]
  • Humphrey Visual Field Test Cumulative Score Change From Baseline [ Time Frame: 2-years ] [ Designated as safety issue: No ]
    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.

  • Frequency of Vitrectomy [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]
  • Mean Change in OCT Central Subfield Thickness From Baseline [ Time Frame: 2-years ] [ Designated as safety issue: No ]
    All baseline and 2-year optical coherence tomography (OCT) scans were evaluated by the OCT reading center.

  • Development of Central DME With Vision Impairment by 2-years [ Time Frame: 2-years ] [ Designated as safety issue: No ]
  • Number of Eyes With Vitreous Hemorrhage [ Time Frame: 2-years ] [ Designated as safety issue: Yes ]
  • Number of Eyes Without Active or Regressed Neovascularization on Fundus Photography at 2-years [ Time Frame: 2-years ] [ Designated as safety issue: No ]
  • Treatment and Follow-up Costs [ Time Frame: 2-years ] [ Designated as safety issue: No ]
  • Number of Eyes With Greater Than or Equal to 10 Letter Vision Loss [ Time Frame: 2-year ] [ Designated as safety issue: No ]

Enrollment: 305
Study Start Date: March 2012
Estimated Study Completion Date: December 2017
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Anti-VEGF+Deferred PRP
Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.
Drug: 0.5-mg Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.
Other: Deferred panretinal photocoagulation
PRP is deferred until failure/futility criteria for intravitreal injection are met.
Active Comparator: Prompt PRP
PRP= Panretinal Photocoagulation. PRP alone.
Other: Prompt Panretinal Photocoagulation
Panretinal photocoagulation alone at baseline (full session completed within 56 days).

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01489189

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

Publications:
Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT01489189     History of Changes
Other Study ID Numbers: DRCR.net Protocol S 
Study First Received: December 6, 2011
Results First Received: February 12, 2016
Last Updated: August 25, 2016
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Retinal Diseases
Diabetic Retinopathy
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Ranibizumab
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 23, 2016