Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema

NCT00444600 | Completed Phase 3 Results DMC

• 4 other identifiers: NEI-133U10EY018817-03U10EY014229-07U10EY014231-09
• Study Type: interventional
• Target: 691
• Locations: 1 country
• Sites: 50

Brief Summary

The purpose of the study is to find out which is a better treatment for diabetic macular edema (DME): laser alone, laser combined with an intravitreal injection of triamcinolone, laser combined with an intravitreal injection of ranibizumab, or intravitreal injection of ranibizumab alone. At the present time, it is not known whether intravitreal steroid or anti-vascular endothelial growth factor (anti-VEGF) injections, with or without laser treatment, are better than just laser by itself. It is possible that one or both of the types of injections, with or without laser treatment, will improve vision more often than will laser without injections. However, even if better vision outcomes are seen with injections, side effects may be more of a problem with the injections than with laser. Therefore, this study is conducted to find out whether the benefits of the injections will outweigh the risks.

Conditions

Diabetic Retinopathy; Diabetic Macular Edema

Keywords

Diabetic Retinopathy; Diabetic Macular Edema; Lucentis; Ranibizumab; Triamcinolone; Laser photocoagulation; Combination Therapy

Outcome Measures

Primary Outcomes (8)

• Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity

  Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  from baseline to 1 Year

• Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year

  Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method.

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score

  Change in best correct visual acuity letter score as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness

  Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity

  Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  from baseline to 1 Year

• Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator

  Change in best correct visual acuity letter score from baseline to one year as measured by a certified tester using an electronic visual acuity testing machine based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method. A positive change denotes an improvement. Best value on the scale 97, worst 0.

  from baseline to 1 Year

Secondary Outcomes (6)

• Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year

  from baseline to 1 year

• Number of Injections in First Year

  from baseline to 1 year

• Number of Laser Treatments Received Prior to the 1 Year Visit

  1 Year

• Percentage of Eyes Receiving Laser at the 48 Week Visit (%)

  1 Year

• Mean Optical Coherence Tomography Retinal Volume at 1 Year

  1 Year

Other Outcomes (7)

• Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year

  1 Year

• Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening

  1 Year

• Eyes With Alternative Treatments Prior to the 1-year Visit

  1 Year

Study Arms (4)

0.5mg Ranibizumab plus laser

EXPERIMENTAL

Drug: Ranibizumab + laser

0.5 mg Ranibizumab plus deferred laser

EXPERIMENTAL

Drug: Ranibizumab + deferred laser

4 mg Triamcinolone plus laser

EXPERIMENTAL

Drug: Triamcinolone Acetonide + laser

Sham plus laser

ACTIVE COMPARATOR

Drug: Sham injection + laser

Interventions

Triamcinolone Acetonide + laser DRUG

4 mg intravitreal triamcinolone at randomization plus focal photocoagulation 1 week post-injection, repeated every 16 weeks with sham injections at 4-week intervals in-between. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Also known as: corticosteroid

4 mg Triamcinolone plus laser

Ranibizumab + laser DRUG

0.5 mg intravitreal ranibizumab at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Also known as: Lucentis, anti-VEGF drug

0.5mg Ranibizumab plus laser

Sham injection + laser DRUG

Sham injection at randomization plus focal photocoagulation 1 week post-injection. Injections are repeated every 4 weeks with focal photocoagulation given post-injection every 16 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT.

Also known as: placebo

Sham plus laser

Ranibizumab + deferred laser DRUG

0.5 mg intravitreal ranibizumab at randomization, repeated every 4 weeks. Retreatment starting at 16 weeks depends on visual acuity and OCT. If improvement has not occured from injections alone, laser can be given starting at the 24 week visit.

Also known as: Lucentis, anti-VEGF drug

0.5 mg Ranibizumab plus deferred 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)
• At least one eye meets the study eye criteria
• Fellow eye (if not a study eye) meets criteria
• Able and willing to provide informed consent

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 drug.
• 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 growth factor (anti-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 first 12 months of the study.
• Best corrected electronic Early Treatment Diabetic Retinopathy (E-ETDRS) visual acuity letter score \<= 78 (i.e., 20/32 or worse) and \>= 24 (i.e., 20/320 or better) within 8 days of randomization.
• On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
• Ocular coherence tomography (OCT) central subfield \>=250 microns within 8 days of randomization.
• Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
• If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

Sponsors & Collaborators

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

Study Sites (50)

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

Retina Vitreous Consultants

Fort Lauderdale, Florida, 33334, United States

Location

Retina Consultants of Southwest Florida

Fort Myers, Florida, 33912, United States

Location

University of Florida College of Med., Department of Ophthalmology

Jacksonville, Florida, 32209, United States

Location

Central Florida Retina Institute

Lakeland, Florida, 33805, United States

Location

Southeast Retina Center, P.C.

Augusta, Georgia, 30909, 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

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

Wilmer Eye 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

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

Wake Forest University Eye Center

Winston-Salem, North Carolina, 27157, United States

Location

Retina Associates of Cleveland, Inc.

Beachwood, Ohio, 44122, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, 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

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

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

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (17)

• 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 BACKGROUND

• 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, Odia I, Glassman AR, Danis RP, Grover S, Hampton GR, Jampol LM, Maguire MG, Melia M. CHANGES IN DIABETIC RETINOPATHY SEVERITY WHEN TREATING DIABETIC MACULAR EDEMA WITH RANIBIZUMAB: DRCR.net Protocol I 5-Year Report. Retina. 2018 Oct;38(10):1896-1904. doi: 10.1097/IAE.0000000000002302.

  PMID: 30234859 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

• Bressler SB, Ayala AR, Bressler NM, Melia M, Qin H, Ferris FL 3rd, Flaxel CJ, Friedman SM, Glassman AR, Jampol LM, Rauser ME; Diabetic Retinopathy Clinical Research Network. Persistent Macular Thickening After Ranibizumab Treatment for Diabetic Macular Edema With Vision Impairment. JAMA Ophthalmol. 2016 Mar;134(3):278-85. doi: 10.1001/jamaophthalmol.2015.5346.

  PMID: 26746868 BACKGROUND

• 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

• 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

• 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

Related Links

• DRCR Retina Network

MeSH Terms

Conditions

Diabetic Retinopathy

Interventions

Triamcinolone Acetonide; Lasers; Adrenal Cortex Hormones; Ranibizumab; 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)

Triamcinolone; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 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 R. Glassman, Director DRCR.net Coordinating Center
• Organization: Jaeb Center for Health Research

drcrnet@jaeb.org

813-975-8690

Study Officials

• Michael J. Elman, M.D.

  Elman Retina Group, PA

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: December 1, 2009
• Study Completion: February 1, 2014
• Last Updated: October 7, 2019
• Results First Posted: July 12, 2011

Record last verified: 2019-09

Locations

US (50)