Prompt Panretinal Photocoagulation Versus Ranibizumab+Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Phase 3

Completed

Conditions: Proliferative Diabetic Retinopathy

Interventions: Drug: 0.5-mg Ranibizumab
Other: Prompt Panretinal Photocoagulation
Other: Deferred panretinal photocoagulation

Registration Number: NCT01489189

Lead Sponsor: Jaeb Center for Health Research

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 305

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Anti-VEGF+Deferred PRP	0.5-mg Ranibizumab	Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.
Prompt PRP	Prompt Panretinal Photocoagulation	PRP= Panretinal Photocoagulation. PRP alone.
Anti-VEGF+Deferred PRP	Deferred panretinal photocoagulation	Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.

Primary Outcome Measures

Name	Time	Method
Mean Change in Visual Acuity From Baseline	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.

Secondary Outcome Measures

Name	Time	Method
Development of Central DME With Vision Impairment by 2-years	2-years
Number of Eyes With Greater Than or Equal to 10 Letter Vision Loss	2-year
Frequency of Vitrectomy	2-years
Number of Eyes With Greater Than or Equal to 10 Letter Vision Gain	2-years
Mean Change in OCT Central Subfield Thickness From Baseline	2-years	All baseline and 2-year optical coherence tomography (OCT) scans were evaluated by the OCT reading center.
Humphrey Visual Field Test Cumulative Score Change From Baseline	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.
Number of Eyes With Vitreous Hemorrhage	2-years
Number of Eyes Without Active or Regressed Neovascularization on Fundus Photography at 2-years	2-years
Mean Visual Acuity	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.

Trial Locations

Locations (47): Retina Associates of Sarasota
🇺🇸
Venice, Florida, United States
Retina and Vitreous Associates of Kentucky
🇺🇸
Lexington, Kentucky, United States
Ocala Eye Retina Consultants
🇺🇸
Ocala, Florida, United States
Retina Vitrous Center
🇺🇸
Grand Blanc, Michigan, United States
Vitreo-Retinal Associates, PC
🇺🇸
Worcester, Massachusetts, United States
Fort Lauderdale Eye Institute
🇺🇸
Plantation, Florida, United States
Carolina Retina Center
🇺🇸
Columbia, South Carolina, United States
Southeastern Retina Associates, PC
🇺🇸
Kingsport, Tennessee, United States
Retina Consultants of Southwest Florida
🇺🇸
Fort Myers, Florida, United States
Central Florida Retina Institute
🇺🇸
Lakeland, Florida, United States
Eye Surgical Associates
🇺🇸
Lincoln, Nebraska, United States
Southeastern Retina Associates, P.C.
🇺🇸
Knoxville, Tennessee, United States
Retina and Vitreous of Texas
🇺🇸
Houston, Texas, United States
Baylor Eye Physicians and Surgeons
🇺🇸
Houston, Texas, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
Southern California Desert Retina Consultants, MC
🇺🇸
Palm Springs, California, United States
Loma Linda University Health Care, Dept. of Ophthalmology
🇺🇸
Loma Linda, California, United States
California Retina Consultants
🇺🇸
Santa Barbara, California, United States
Southeast Retina Center, P.C.
🇺🇸
Augusta, Georgia, United States
Bay Area Retina Associates
🇺🇸
Walnut Creek, California, United States
North Shore University Health System
🇺🇸
Glenview, Illinois, United States
Wolfe Eye Clinic
🇺🇸
West Des Moines, Iowa, United States
John-Kenyon American Eye Institute
🇺🇸
New Albany, Indiana, United States
Paducah Retinal Center
🇺🇸
Paducah, Kentucky, United States
Barnes Retina Institute
🇺🇸
Saint Louis, Missouri, United States
The New York Eye and Ear Infirmary/Faculty Eye Practice
🇺🇸
New York, New York, United States
University of Rochester
🇺🇸
Rochester, New York, United States
Retina-Vitreous Surgeons of Central New York, PC
🇺🇸
Syracuse, New York, United States
Charlotte Eye, Ear, Nose and Throat Assoc., PA
🇺🇸
Charlotte, North Carolina, United States
Penn State College of Medicine
🇺🇸
Hershey, Pennsylvania, United States
Retina Associates of Cleveland, Inc.
🇺🇸
Beachwood, Ohio, United States
Family Eye Group
🇺🇸
Lancaster, Pennsylvania, United States
Retina Vitrous Consultants
🇺🇸
Pittsburgh, Pennsylvania, United States
Valley Retina Institute
🇺🇸
McAllen, Texas, United States
Spokane Eye Clinic
🇺🇸
Spokane, Washington, United States
Texas Retina Associates
🇺🇸
Lubbock, Texas, United States
Retinal Consultants of AZ
🇺🇸
Phoenix, Arizona, United States
Raj K. Maturi, M.D., P.C.
🇺🇸
Indianapolis, Indiana, United States
Retinal Consultants of San Antonio
🇺🇸
San Antonio, Texas, United States
Retina Northwest, PC
🇺🇸
Portland, Oregon, United States
Casey Eye Institute
🇺🇸
Portland, Oregon, United States
Medical College of Wiconsin
🇺🇸
Milwaukee, Wisconsin, United States
New England Retina Associates
🇺🇸
Trumbull, Connecticut, United States
Elman Retina Group, P.A.
🇺🇸
Baltimore, Maryland, United States
Austin Retina Associates
🇺🇸
Austin, Texas, United States
University of North Carolina
🇺🇸
Chapel Hill, North Carolina, United States
Retina Research Center
🇺🇸
Austin, Texas, United States