Laser-Ranibizumab-Triamcinolone for Proliferative Diabetic Retinopathy

NCT00445003 | Completed Phase 3 Results DMC

• 4 other identifiers: NEI-134U10EY018817-03U10EY014229-07U10EY014231-09
• Study Type: interventional
• Target: 333
• Locations: 1 country
• Sites: 56

Brief Summary

The purpose of the study is to find out if treatment with an intravitreal injection of triamcinolone or an intravitreal injection of ranibizumab can prevent loss of vision caused by panretinal photocoagulation treatment. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections are beneficial in preventing vision loss after panretinal photocoagulation (PRP) treatment. It is possible that one or both of the types of injections will prevent vision loss after PRP treatment. However, it is not known whether the benefits of the injections will outweigh the risks. It is possible that because of side effects, the injections may not be as good as laser alone in treating the diabetic retinopathy.

Conditions

Proliferative Diabetic Retinopathy; Diabetic Macular Edema

Keywords

Diabetic Retinopathy; Diabetic Macular Edema; Lucentis; Ranibizumab; Triamcinolone; Panretinal Photocoagulation; Combination Therapy; pdr

Outcome Measures

Primary Outcomes (1)

• Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 14 Weeks

  Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.

  baseline to 14 weeks

Secondary Outcomes (7)

• Additional Treatments for Diabetic Macular Edema

  14 weeks to 56-weeks

• Change in Optical Coherence Tomography Central Subfield Thickness

  Baseline to 14 weeks

• Total Optical Coherence Tomography Retinal Volume

  Baseline to 14-weeks

• Change in Visual Acuity From Baseline

  baseline to 56-weeks

• Eyes With Anti-vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema

  14 weeks to 56-weeks

Study Arms (3)

Sham injection plus laser

EXPERIMENTAL

Sham injection at baseline and 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.

Behavioral: Sham injection; Procedure: Focal/grid laser

0.5mg Ranibizumab plus laser

EXPERIMENTAL

Intravitreal injections of 0.5mg Ranibizumab at baseline and at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.

Drug: Ranibizumab; Procedure: Focal/grid laser

4-mg Triamcinolone Acetonide plus Laser

ACTIVE COMPARATOR

4-mg Triamcinolone Acetonide at baseline and sham injection at 4 weeks. Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.

Drug: Triamcinolone Acetonide; Procedure: Focal/grid laser

Interventions

Ranibizumab DRUG

Intravitreal injection of 0.5 mg ranibizumab at baseline and 4 weeks

Also known as: Lucentis™

0.5mg Ranibizumab plus laser

Triamcinolone Acetonide DRUG

Intravitreal injection of 4 mg triamcinolone acetonide at baseline and sham injection at 4 weeks

Also known as: corticosteroid

4-mg Triamcinolone Acetonide plus Laser

Sham injection BEHAVIORAL

Sham injection at baseline and 4 weeks

Sham injection plus laser

Focal/grid laser PROCEDURE

Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.

0.5mg Ranibizumab plus laser; 4-mg Triamcinolone Acetonide plus Laser; Sham injection plus laser

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
• Diagnosis of diabetes mellitus (type 1 or type 2)
• Fellow eye (if not a study eye) meets criteria.
• Presence of severe nonproliferative or proliferative diabetic retinopathy for which investigator intends to complete panretinal photocoagulation within 49 days after randomization.
• Diabetic macular edema(DME) present on clinical exam and central subfield thickness on Optical Coherence Tomography (OCT) \>250 microns, within 8 days of randomization.
• Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score \>=24 (i.e., 20/320 or better), within 8 days of randomization.
• Media clarity, pupillary dilation, and subject cooperation sufficient to administer panretinal photocoagulation and obtain adequate fundus photographs and OCT.
• If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional focal photocoagulation.

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).
• Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
• Known allergy to any component of the study drugs.
• Blood pressure \> 180/110 (systolic above 180 or diastolic above 110).
• Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
• Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
• Systemic anti-vascular endothelial growth factor(VEGF) or pro-VEGF treatment within 4 months prior to randomization.
• For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
• Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 12 months of the study.
• Prior panretinal photocoagulation that was sufficiently extensive that the investigator does not believe that at least 1200 additional burns are needed or possible within 49 days after randomization.
• Macular edema is considered to be due to a cause other than diabetic macular edema.
• An ocular condition is present such that, in the opinion of the investigator, preventing visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal condition).
• An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or 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.).
• 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 was otherwise normal).

Sponsors & Collaborators

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

Study Sites (56)

Sall Research Medical Center

Artesia, California, 90701, United States

Location

Retina-Vitreous Associates Medical Group

Beverly Hills, California, 90211, United States

Location

University of California, Irvine

Irvine, California, 92697, 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

Eldorado Retina Associates, P.C.

Louisville, Colorado, 80027, United States

Location

Retina Vitreous Consultants

Fort Lauderdale, Florida, 33334, 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

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, United States

Location

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

Illinois Retina Associates

Joliet, Illinois, 60435, United States

Location

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

Indianapolis, Indiana, 46280, United States

Location

John-Kenyon American Eye Institute

New Albany, Indiana, 47150, United States

Location

Medical Associates Clinic, P.C.

Dubuque, Iowa, 52002, United States

Location

Paducah Retinal Center

Paducah, Kentucky, 42001, United States

Location

Maine Vitreoretinal Consultants

Bangor, Maine, 04401, United States

Location

Elman Retina Group, P.A.

Baltimore, Maryland, 21237, United States

Location

Wilmer Ophthalmological Institute at Johns Hopkins

Baltimore, Maryland, 21287-9277, United States

Location

Retina Consultants of Delmarva, P.A.

Salisbury, Maryland, 21801, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

Location

Retina Center, PA

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Eyesight Ophthalmic Services, PA

Portsmouth, New Hampshire, 03801, United States

Location

The New York Eye and Ear Infirmary/Faculty Eye Practice

New York, New York, 10003, United States

Location

Retina-Vitreous Surgeons of Central New York, PC

Syracuse, New York, 13224, United States

Location

University of North Carolina, Dept of Ophthalmology

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

Location

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

Charlotte, North Carolina, 28210, United States

Location

Horizon Eye Care, PA

Charlotte, North Carolina, 28211, United States

Location

Wake Forest University Eye Center

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

OSU Eye Physicians and Surgeons, LLC.

Dublin, Ohio, 43017, 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

University of Pennsylvania Scheie Eye Institute

Philadelphia, Pennsylvania, 19104, United States

Location

Retina Consultants

Providence, Rhode Island, 02903, United States

Location

Palmetto Retina Center

Columbia, South Carolina, 29169, 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

West Texas Retina Consultants P.A.

Abilene, Texas, 79605, United States

Location

Texas Retina Associates

Arlington, Texas, 76012, 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

Vitreoretinal Consultants

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

Virginia Retina Center

Leesburg, Virginia, 20176, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

University of Wisconsin-Madison, Dept of Ophthalmology/Retina Service

Madison, Wisconsin, 53705, United States

Location

Related Publications (14)

• Diabetic Retinopathy Clinical Research Network; Writing Committee; Aiello LP, Beck RW, Bressler NM, Browning DJ, Chalam KV, Davis M, Ferris FL 3rd, Glassman AR, Maturi RK, Stockdale CR, Topping TM. Rationale for the diabetic retinopathy clinical research network treatment protocol for center-involved diabetic macular edema. Ophthalmology. 2011 Dec;118(12):e5-14. doi: 10.1016/j.ophtha.2011.09.058.

  PMID: 22136692 BACKGROUND

• Glassman AR, Stockdale CR, Beck RW, Baker C, Bressler NM; Diabetic Retinopathy Clinical Research Network. Evaluation of masking study participants to intravitreal injections in a randomized clinical trial. Arch Ophthalmol. 2012 Feb;130(2):190-4. doi: 10.1001/archophthalmol.2011.387.

  PMID: 22332211 BACKGROUND

• Bressler SB, Qin H, Beck RW, Chalam KV, Kim JE, Melia M, Wells JA 3rd; Diabetic Retinopathy Clinical Research Network. Factors associated with changes in visual acuity and central subfield thickness at 1 year after treatment for diabetic macular edema with ranibizumab. Arch Ophthalmol. 2012 Sep;130(9):1153-61. doi: 10.1001/archophthalmol.2012.1107.

  PMID: 22965591 BACKGROUND

• Bressler SB, Qin H, Melia M, Bressler NM, Beck RW, Chan CK, Grover S, Miller DG; Diabetic Retinopathy Clinical Research Network. Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial. JAMA Ophthalmol. 2013 Aug;131(8):1033-40. doi: 10.1001/jamaophthalmol.2013.4154.

  PMID: 23807371 BACKGROUND

• Bressler SB, Almukhtar T, Aiello LP, Bressler NM, Ferris FL 3rd, Glassman AR, Greven CM; Diabetic Retinopathy Clinical Research Network. Green or yellow laser treatment for diabetic macular edema: exploratory assessment within the Diabetic Retinopathy Clinical Research Network. Retina. 2013 Nov-Dec;33(10):2080-8. doi: 10.1097/IAE.0b013e318295f744.

  PMID: 23792486 BACKGROUND

• Bressler SB, Almukhtar T, Bhorade A, Bressler NM, Glassman AR, Huang SS, Jampol LM, Kim JE, Melia M; Diabetic Retinopathy Clinical Research Network Investigators. Repeated intravitreous ranibizumab injections for diabetic macular edema and the risk of sustained elevation of intraocular pressure or the need for ocular hypotensive treatment. JAMA Ophthalmol. 2015 May;133(5):589-97. doi: 10.1001/jamaophthalmol.2015.186.

  PMID: 25719991 BACKGROUND

• Bressler SB, Melia M, Glassman AR, Almukhtar T, Jampol LM, Shami M, Berger BB, Bressler NM; Diabetic Retinopathy Clinical Research Network. RANIBIZUMAB PLUS PROMPT OR DEFERRED LASER FOR DIABETIC MACULAR EDEMA IN EYES WITH VITRECTOMY BEFORE ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY. Retina. 2015 Dec;35(12):2516-28. doi: 10.1097/IAE.0000000000000617.

  PMID: 26035510 BACKGROUND

• Elman MJ, Bressler NM, Qin H, Beck RW, Ferris FL 3rd, Friedman SM, Glassman AR, Scott IU, Stockdale CR, Sun JK; Diabetic Retinopathy Clinical Research Network. Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2011 Apr;118(4):609-14. doi: 10.1016/j.ophtha.2010.12.033.

  PMID: 21459214 RESULT

• Diabetic Retinopathy Clinical Research Network; Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. doi: 10.1016/j.ophtha.2010.02.031. Epub 2010 Apr 28.

  PMID: 20427088 RESULT

• Diabetic Retinopathy Clinical Research Network; Elman MJ, Qin H, Aiello LP, Beck RW, Bressler NM, Ferris FL 3rd, Glassman AR, Maturi RK, Melia M. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012 Nov;119(11):2312-8. doi: 10.1016/j.ophtha.2012.08.022. Epub 2012 Sep 19.

  PMID: 22999634 RESULT

• Bressler SB, Glassman AR, Almukhtar T, Bressler NM, Ferris FL, Googe JM Jr, Gupta SK, Jampol LM, Melia M, Wells JA 3rd; Diabetic Retinopathy Clinical Research Network. Five-Year Outcomes of Ranibizumab With Prompt or Deferred Laser Versus Laser or Triamcinolone Plus Deferred Ranibizumab for Diabetic Macular Edema. Am J Ophthalmol. 2016 Apr;164:57-68. doi: 10.1016/j.ajo.2015.12.025. Epub 2016 Jan 21.

  PMID: 26802783 RESULT

• Elman MJ, Ayala A, Bressler NM, Browning D, Flaxel CJ, Glassman AR, Jampol LM, Stone TW; Diabetic Retinopathy Clinical Research Network. Intravitreal Ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: 5-year randomized trial results. Ophthalmology. 2015 Feb;122(2):375-81. doi: 10.1016/j.ophtha.2014.08.047. Epub 2014 Oct 28.

  PMID: 25439614 RESULT

• Gangaputra S, Almukhtar T, Glassman AR, Aiello LP, Bressler N, Bressler SB, Danis RP, Davis MD; Diabetic Retinopathy Clinical Research Network. Comparison of film and digital fundus photographs in eyes of individuals with diabetes mellitus. Invest Ophthalmol Vis Sci. 2011 Aug 3;52(9):6168-73. doi: 10.1167/iovs.11-7321.

  PMID: 21571677 DERIVED

• Bhavsar AR, Googe JM Jr, Stockdale CR, Bressler NM, Brucker AJ, Elman MJ, Glassman AR; Diabetic Retinopathy Clinical Research Network. Risk of endophthalmitis after intravitreal drug injection when topical antibiotics are not required: the diabetic retinopathy clinical research network laser-ranibizumab-triamcinolone clinical trials. Arch Ophthalmol. 2009 Dec;127(12):1581-3. doi: 10.1001/archophthalmol.2009.304.

  PMID: 20008710 DERIVED

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Ranibizumab; Triamcinolone Acetonide; Adrenal Cortex Hormones; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Adam R. Glassman, Director DRCR.net Coordinating Center
• Organization: Jaeb Center for Health Research

aglassman@jaeb.org

813-975-8690

Study Officials

• Alexander J. Brucker, M.D.

  Scheie Eye Institute

  STUDY CHAIR

• Joseph Googe, Jr., M.D.

  Southeastern Retina Associates, P.C.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2007
• First Posted: March 8, 2007
• Study Start: March 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: July 1, 2010
• Last Updated: August 26, 2016
• Results First Posted: July 13, 2011

Record last verified: 2016-08

Locations

US (56)