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

NCT ID: NCT01489189

Last Updated: 2021-10-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

305 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-31

Study Completion Date

2018-02-05

Brief Summary

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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

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Conditions

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Proliferative Diabetic Retinopathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Anti-VEGF+Deferred PRP

Anti-VEGF= Anti vascular endothelial growth factor. PRP= Panretinal photocoagulation. Intravitreal anti-VEGF with PRP only if indicated.

Group Type EXPERIMENTAL

0.5-mg Ranibizumab

Intervention Type DRUG

Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.

Deferred panretinal photocoagulation

Intervention Type OTHER

PRP is deferred until failure/futility criteria for intravitreal injection are met.

Prompt PRP

PRP= Panretinal Photocoagulation. PRP alone.

Group Type ACTIVE_COMPARATOR

Prompt Panretinal Photocoagulation

Intervention Type OTHER

Panretinal photocoagulation alone at baseline (full session completed within 56 days).

Interventions

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Prompt Panretinal Photocoagulation

Panretinal photocoagulation alone at baseline (full session completed within 56 days).

Intervention Type OTHER

0.5-mg Ranibizumab

Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.

Intervention Type DRUG

Deferred panretinal photocoagulation

PRP is deferred until failure/futility criteria for intravitreal injection are met.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Eye Institute (NEI)

NIH

Sponsor Role collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role collaborator

Jaeb Center for Health Research

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeffrey G Gross, MD

Role: STUDY_CHAIR

Carolina Retina Center

Locations

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Retinal Consultants of AZ

Phoenix, Arizona, United States

Site Status

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, United States

Site Status

Southern California Desert Retina Consultants, MC

Palm Springs, California, United States

Site Status

California Retina Consultants

Santa Barbara, California, United States

Site Status

Bay Area Retina Associates

Walnut Creek, California, United States

Site Status

New England Retina Associates

Trumbull, Connecticut, United States

Site Status

Retina Consultants of Southwest Florida

Fort Myers, Florida, United States

Site Status

Central Florida Retina Institute

Lakeland, Florida, United States

Site Status

Ocala Eye Retina Consultants

Ocala, Florida, United States

Site Status

Fort Lauderdale Eye Institute

Plantation, Florida, United States

Site Status

Retina Associates of Sarasota

Venice, Florida, United States

Site Status

Southeast Retina Center, P.C.

Augusta, Georgia, United States

Site Status

North Shore University Health System

Glenview, Illinois, United States

Site Status

Raj K. Maturi, M.D., P.C.

Indianapolis, Indiana, United States

Site Status

John-Kenyon American Eye Institute

New Albany, Indiana, United States

Site Status

Wolfe Eye Clinic

West Des Moines, Iowa, United States

Site Status

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, United States

Site Status

Paducah Retinal Center

Paducah, Kentucky, United States

Site Status

Elman Retina Group, P.A.

Baltimore, Maryland, United States

Site Status

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, United States

Site Status

Retina Vitrous Center

Grand Blanc, Michigan, United States

Site Status

Barnes Retina Institute

St Louis, Missouri, United States

Site Status

Eye Surgical Associates

Lincoln, Nebraska, United States

Site Status

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Charlotte Eye, Ear, Nose and Throat Assoc., PA

Charlotte, North Carolina, United States

Site Status

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, United States

Site Status

Retina Northwest, PC

Portland, Oregon, United States

Site Status

Casey Eye Institute

Portland, Oregon, United States

Site Status

Penn State College of Medicine

Hershey, Pennsylvania, United States

Site Status

Family Eye Group

Lancaster, Pennsylvania, United States

Site Status

Retina Vitrous Consultants

Pittsburgh, Pennsylvania, United States

Site Status

Carolina Retina Center

Columbia, South Carolina, United States

Site Status

Southeastern Retina Associates, PC

Kingsport, Tennessee, United States

Site Status

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, United States

Site Status

Austin Retina Associates

Austin, Texas, United States

Site Status

Retina Research Center

Austin, Texas, United States

Site Status

Texas Retina Associates

Dallas, Texas, United States

Site Status

Retina and Vitreous of Texas

Houston, Texas, United States

Site Status

Baylor Eye Physicians and Surgeons

Houston, Texas, United States

Site Status

Texas Retina Associates

Lubbock, Texas, United States

Site Status

Valley Retina Institute

McAllen, Texas, United States

Site Status

Retinal Consultants of San Antonio

San Antonio, Texas, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Spokane Eye Clinic

Spokane, Washington, United States

Site Status

Medical College of Wiconsin

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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Gross JG, Glassman AR. A Novel Treatment for Proliferative Diabetic Retinopathy: Anti-Vascular Endothelial Growth Factor Therapy. JAMA Ophthalmol. 2016 Jan;134(1):13-4. doi: 10.1001/jamaophthalmol.2015.5079. No abstract available.

Reference Type BACKGROUND
PMID: 26583372 (View on PubMed)

Gross JG, Glassman AR. Panretinal Photocoagulation vs Anti-Vascular Endothelial Growth Factor for Proliferative Diabetic Retinopathy-Reply. JAMA Ophthalmol. 2016 Jun 1;134(6):716. doi: 10.1001/jamaophthalmol.2016.0703. No abstract available.

Reference Type BACKGROUND
PMID: 27101313 (View on PubMed)

Beaulieu WT, Bressler NM, Melia M, Owsley C, Mein CE, Gross JG, Jampol LM, Glassman AR; Diabetic Retinopathy Clinical Research Network. Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Patient-Centered Outcomes From a Randomized Clinical Trial. Am J Ophthalmol. 2016 Oct;170:206-213. doi: 10.1016/j.ajo.2016.08.008. Epub 2016 Aug 12.

Reference Type BACKGROUND
PMID: 27523491 (View on PubMed)

Bressler SB, Beaulieu WT, Glassman AR, Gross JG, Jampol LM, Melia M, Peters MA, Rauser ME; Diabetic Retinopathy Clinical Research Network. Factors Associated with Worsening Proliferative Diabetic Retinopathy in Eyes Treated with Panretinal Photocoagulation or Ranibizumab. Ophthalmology. 2017 Apr;124(4):431-439. doi: 10.1016/j.ophtha.2016.12.005. Epub 2017 Feb 1.

Reference Type BACKGROUND
PMID: 28161147 (View on PubMed)

Hutton DW, Stein JD, Bressler NM, Jampol LM, Browning D, Glassman AR; Diabetic Retinopathy Clinical Research Network. Cost-effectiveness of Intravitreous Ranibizumab Compared With Panretinal Photocoagulation for Proliferative Diabetic Retinopathy: Secondary Analysis From a Diabetic Retinopathy Clinical Research Network Randomized Clinical Trial. JAMA Ophthalmol. 2017 Jun 1;135(6):576-584. doi: 10.1001/jamaophthalmol.2017.0837.

Reference Type BACKGROUND
PMID: 28492920 (View on PubMed)

Gross JG, Glassman AR, Klein MJ, Jampol LM, Ferris FL 3rd, Bressler NM, Beck RW. Interim Safety Data Comparing Ranibizumab With Panretinal Photocoagulation Among Participants With Proliferative Diabetic Retinopathy. JAMA Ophthalmol. 2017 Jun 1;135(6):672-673. doi: 10.1001/jamaophthalmol.2017.0969.

Reference Type BACKGROUND
PMID: 28492921 (View on PubMed)

Jampol LM, Odia I, Glassman AR, Baker CW, Bhorade AM, Han DP, Jaffe GJ, Melia M, Bressler NM, Tanna AP; Diabetic Retinopathy Clinical Research Network. PANRETINAL PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Comparison of Peripapillary Retinal Nerve Fiber Layer Thickness in a Randomized Clinical Trial. Retina. 2019 Jan;39(1):69-78. doi: 10.1097/IAE.0000000000001909.

Reference Type BACKGROUND
PMID: 29135802 (View on PubMed)

Bressler SB, Beaulieu WT, Glassman AR, Gross JG, Melia M, Chen E, Pavlica MR, Jampol LM; Diabetic Retinopathy Clinical Research Network. Panretinal Photocoagulation Versus Ranibizumab for Proliferative Diabetic Retinopathy: Factors Associated with Vision and Edema Outcomes. Ophthalmology. 2018 Nov;125(11):1776-1783. doi: 10.1016/j.ophtha.2018.04.039. Epub 2018 Jul 3.

Reference Type BACKGROUND
PMID: 29980333 (View on PubMed)

Gross JG, Glassman AR, Liu D, Sun JK, Antoszyk AN, Baker CW, Bressler NM, Elman MJ, Ferris FL 3rd, Gardner TW, Jampol LM, Martin DF, Melia M, Stockdale CR, Beck RW; Diabetic Retinopathy Clinical Research Network. Five-Year Outcomes of Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2018 Oct 1;136(10):1138-1148. doi: 10.1001/jamaophthalmol.2018.3255.

Reference Type BACKGROUND
PMID: 30043039 (View on PubMed)

Sun JK, Glassman AR, Beaulieu WT, Stockdale CR, Bressler NM, Flaxel C, Gross JG, Shami M, Jampol LM; Diabetic Retinopathy Clinical Research Network. Rationale and Application of the Protocol S Anti-Vascular Endothelial Growth Factor Algorithm for Proliferative Diabetic Retinopathy. Ophthalmology. 2019 Jan;126(1):87-95. doi: 10.1016/j.ophtha.2018.08.001. Epub 2018 Aug 7.

Reference Type BACKGROUND
PMID: 30096354 (View on PubMed)

Bressler SB, Beaulieu WT, Glassman AR, Gross JG, Melia M, Chen E, Pavlica MR, Jampol LM; Diabetic Retinopathy Clinical Research Network. PHOTOCOAGULATION VERSUS RANIBIZUMAB FOR PROLIFERATIVE DIABETIC RETINOPATHY: Should Baseline Characteristics Affect Choice of Treatment? Retina. 2019 Sep;39(9):1646-1654. doi: 10.1097/IAE.0000000000002377.

Reference Type BACKGROUND
PMID: 30807516 (View on PubMed)

Glassman AR, Beaulieu WT, Stockdale CR, Beck RW, Bressler NM, Labriola LT, Melia M, Oliver K, Sun JK. Effect of telephone calls from a centralized coordinating center on participant retention in a randomized clinical trial. Clin Trials. 2020 Apr;17(2):195-201. doi: 10.1177/1740774519894229. Epub 2020 Jan 27.

Reference Type BACKGROUND
PMID: 31984762 (View on PubMed)

Maguire MG, Liu D, Glassman AR, Jampol LM, Johnson CA, Baker CW, Bressler NM, Gardner TW, Pieramici D, Stockdale CR, Sun JK; DRCR Retina Network. Visual Field Changes Over 5 Years in Patients Treated With Panretinal Photocoagulation or Ranibizumab for Proliferative Diabetic Retinopathy. JAMA Ophthalmol. 2020 Mar 1;138(3):285-293. doi: 10.1001/jamaophthalmol.2019.5939.

Reference Type BACKGROUND
PMID: 31999300 (View on PubMed)

Hutton DW, Stein JD, Glassman AR, Bressler NM, Jampol LM, Sun JK; DRCR Retina Network. Five-Year Cost-effectiveness of Intravitreous Ranibizumab Therapy vs Panretinal Photocoagulation for Treating Proliferative Diabetic Retinopathy: A Secondary Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2019 Dec 1;137(12):1424-1432. doi: 10.1001/jamaophthalmol.2019.4284.

Reference Type BACKGROUND
PMID: 31647496 (View on PubMed)

Writing Committee for the Diabetic Retinopathy Clinical Research Network; Gross JG, Glassman AR, Jampol LM, Inusah S, Aiello LP, Antoszyk AN, Baker CW, Berger BB, Bressler NM, Browning D, Elman MJ, Ferris FL 3rd, Friedman SM, Marcus DM, Melia M, Stockdale CR, Sun JK, Beck RW. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015 Nov 24;314(20):2137-2146. doi: 10.1001/jama.2015.15217.

Reference Type RESULT
PMID: 26565927 (View on PubMed)

Talcott KE, Valentim CCS, Hill L, Stoilov I, Singh RP. Baseline Diabetic Retinopathy Severity and Time to Diabetic Macular Edema Resolution with Ranibizumab Treatment: A Meta-Analysis. Ophthalmol Retina. 2023 Jul;7(7):605-611. doi: 10.1016/j.oret.2023.02.003. Epub 2023 Feb 10.

Reference Type DERIVED
PMID: 36774994 (View on PubMed)

Maguire MG, Liu D, Bressler SB, Friedman SM, Melia M, Stockdale CR, Glassman AR, Sun JK; DRCR Retina Network. Lapses in Care Among Patients Assigned to Ranibizumab for Proliferative Diabetic Retinopathy: A Post Hoc Analysis of a Randomized Clinical Trial. JAMA Ophthalmol. 2021 Dec 1;139(12):1266-1273. doi: 10.1001/jamaophthalmol.2021.4103.

Reference Type DERIVED
PMID: 34673898 (View on PubMed)

Other Identifiers

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DRCR.net Protocol S

Identifier Type: -

Identifier Source: org_study_id