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

NCT01489189 | Completed Phase 3 Results DMC

• 1 other identifier: DRCR.net Protocol S
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 48

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.

Conditions

Proliferative Diabetic Retinopathy

Outcome Measures

Primary Outcomes (1)

• Mean Change in Visual Acuity From Baseline

  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 Outcomes (9)

• Mean Visual Acuity

  2-years

• Number of Eyes With Greater Than or Equal to 10 Letter Vision Gain

  2-years

• Humphrey Visual Field Test Cumulative Score Change From Baseline

  2-years

• Frequency of Vitrectomy

  2-years

• Mean Change in OCT Central Subfield Thickness From Baseline

  2-years

Study Arms (2)

Anti-VEGF+Deferred PRP

EXPERIMENTAL

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

Drug: 0.5-mg Ranibizumab; Other: Deferred panretinal photocoagulation

Prompt PRP

ACTIVE COMPARATOR

PRP= Panretinal Photocoagulation. PRP alone.

Other: Prompt Panretinal Photocoagulation

Interventions

Prompt Panretinal Photocoagulation OTHER

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

Prompt PRP

0.5-mg Ranibizumab DRUG

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

Anti-VEGF+Deferred PRP

Deferred panretinal photocoagulation OTHER

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

Anti-VEGF+Deferred PRP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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:

Sponsors & Collaborators

• Jaeb Center for Health Research: lead
• National Eye Institute (NEI): collaborator
• Genentech, Inc.: collaborator

Study Sites (48)

Retinal Consultants of AZ

Phoenix, Arizona, 85014, United States

Location

Loma Linda University Health Care, Dept. of Ophthalmology

Loma Linda, California, 92354, United States

Location

Southern California Desert Retina Consultants, MC

Palm Springs, California, 92262, United States

Location

California Retina Consultants

Santa Barbara, California, 93103, United States

Location

Bay Area Retina Associates

Walnut Creek, California, 94598, United States

Location

New England Retina Associates

Trumbull, Connecticut, 06611, United States

Location

Retina Consultants of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

Central Florida Retina Institute

Lakeland, Florida, 33805, United States

Location

Ocala Eye Retina Consultants

Ocala, Florida, 34474, United States

Location

Fort Lauderdale Eye Institute

Plantation, Florida, 33324, United States

Location

Retina Associates of Sarasota

Venice, Florida, 34285, United States

Location

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, United States

Location

North Shore University Health System

Glenview, Illinois, 60026, United States

Location

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

Indianapolis, Indiana, 46290, United States

Location

John-Kenyon American Eye Institute

New Albany, Indiana, 47150, United States

Location

Wolfe Eye Clinic

West Des Moines, Iowa, 50266, United States

Location

Retina and Vitreous Associates of Kentucky

Lexington, Kentucky, 40509-1802, United States

Location

Paducah Retinal Center

Paducah, Kentucky, 42001, United States

Location

Elman Retina Group, P.A.

Baltimore, Maryland, 21237, United States

Location

Vitreo-Retinal Associates, PC

Worcester, Massachusetts, 01605, United States

Location

Retina Vitrous Center

Grand Blanc, Michigan, 48439, United States

Location

Barnes Retina Institute

St Louis, Missouri, 63110, United States

Location

Eye Surgical Associates

Lincoln, Nebraska, 38506, United States

Location

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, 10003, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, 13224, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599-7040, United States

Location

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

Charlotte, North Carolina, 28210, United States

Location

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, 44122, United States

Location

Retina Northwest, PC

Portland, Oregon, 97210, United States

Location

Casey Eye Institute

Portland, Oregon, 97239, United States

Location

Penn State College of Medicine

Hershey, Pennsylvania, 17033, United States

Location

Family Eye Group

Lancaster, Pennsylvania, 17601-2644, United States

Location

Retina Vitrous Consultants

Pittsburgh, Pennsylvania, 15213, United States

Location

Carolina Retina Center

Columbia, South Carolina, 29223, United States

Location

Southeastern Retina Associates, PC

Kingsport, Tennessee, 37660, United States

Location

Southeastern Retina Associates, P.C.

Knoxville, Tennessee, 37909, United States

Location

Austin Retina Associates

Austin, Texas, 78705, United States

Location

Retina Research Center

Austin, Texas, 78705, United States

Location

Texas Retina Associates

Dallas, Texas, 75231, United States

Location

Retina and Vitreous of Texas

Houston, Texas, 77025, United States

Location

Baylor Eye Physicians and Surgeons

Houston, Texas, 77030, United States

Location

Texas Retina Associates

Lubbock, Texas, 79424, United States

Location

Valley Retina Institute

McAllen, Texas, 78503, United States

Location

Retinal Consultants of San Antonio

San Antonio, Texas, 78240, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Spokane Eye Clinic

Spokane, Washington, 99204, United States

Location

Medical College of Wiconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (17)

• 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.

  PMID: 26583372 BACKGROUND

• 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.

  PMID: 27101313 BACKGROUND

• 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.

  PMID: 27523491 BACKGROUND

• 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.

  PMID: 28161147 BACKGROUND

• 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.

  PMID: 28492920 BACKGROUND

• 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.

  PMID: 28492921 BACKGROUND

• 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.

  PMID: 29135802 BACKGROUND

• 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.

  PMID: 29980333 BACKGROUND

• 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. Erratum In: JAMA Ophthalmol. 2019 Apr 1;137(4):467. doi: 10.1001/jamaophthalmol.2019.0032.

  PMID: 30043039 BACKGROUND

• 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.

  PMID: 30096354 BACKGROUND

• 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.

  PMID: 30807516 BACKGROUND

• 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.

  PMID: 31984762 BACKGROUND

• 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.

  PMID: 31999300 BACKGROUND

• 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.

  PMID: 31647496 BACKGROUND

• 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.

  PMID: 26565927 RESULT

• 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.

  PMID: 36774994 DERIVED

• 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.

  PMID: 34673898 DERIVED

MeSH Terms

Interventions

Ranibizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Adam Glassman
• Organization: Jaeb Center for Health Research

drcrnet@jaeb.org

813-975-8690

Study Officials

• Jeffrey G Gross, MD

  Carolina Retina Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2011
• First Posted: December 9, 2011
• Study Start: March 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: February 5, 2018
• Last Updated: October 29, 2021
• Results First Posted: June 1, 2016

Record last verified: 2021-10

Locations

US (48)