Laser-Ranibizumab-Triamcinolone for Proliferative Diabetic Retinopathy (LRTforDME+PRP)

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Allergan
Information provided by (Responsible Party):
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00445003
First received: March 6, 2007
Last updated: January 30, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Proliferative Diabetic Retinopathy
Diabetic Macular Edema
Drug: Ranibizumab
Drug: Triamcinolone Acetonide
Behavioral: Sham injection
Procedure: Focal/grid laser
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Intravitreal Ranibizumab or Triamcinolone Acetonide as Adjunctive Treatment to Panretinal Photocoagulation for Proliferative Diabetic Retinopathy

Resource links provided by NLM:


Further study details as provided by Diabetic Retinopathy Clinical Research Network:

Primary Outcome Measures:
  • Change in Electronic Early Treatment Diabetic Retinopathy Study Visual Acuity Letter Score From Baseline to 14 Weeks [ Time Frame: baseline to 14 weeks ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Additional Treatments for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ] [ Designated as safety issue: No ]
    Each combination of treatment is only counted once per treatment eye. Participants could have 2 study eyes, with random assignments to different treatments.

  • Change in Optical Coherence Tomography Central Subfield Thickness [ Time Frame: Baseline to 14 weeks ] [ Designated as safety issue: No ]
  • Total Optical Coherence Tomography Retinal Volume [ Time Frame: Baseline to 14-weeks ] [ Designated as safety issue: No ]
    Missing/ungradable as follows: Sham = 49, Ranibizumab = 37, Triamcinolone = 39. Visits occured between 70 days and 153 days from randomization adjusted for baseline optical coherence tomography (OCT) retinal volume, OCT retinal thickness and visual acuity, number of planned panretinal photocoagulation sittings, and correlation between 2 study eyes. Confidence intervals are adjusted for multiple comparisons.

  • Change in Visual Acuity From Baseline [ Time Frame: baseline to 56-weeks ] [ Designated as safety issue: No ]
    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.

  • Eyes With Anti-vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ] [ Designated as safety issue: No ]
  • Number of Eyes With Additional Number of Treatments for Diabetic Macular Edema [ Time Frame: 14 weeks to 56-weeks ] [ Designated as safety issue: No ]
    Treatments include any type or combination of treatment for diabetic macular edema. Eyes were only counted once, when receiving a combination of treatments.

  • Change in Optical Coherence Tomography Retinal Volume [ Time Frame: Baseline to 14 weeks ] [ Designated as safety issue: No ]
    Missing or un-gradable data as follows for the sham plus focal/grid/panretinal photocoagulation laser, triamcinolone plus focal/grid panretinal photocoagulation laser, and Ranibizumab groups were 49, 37, and 39, respectively


Enrollment: 333
Study Start Date: March 2007
Study Completion Date: July 2010
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sham injection plus laser
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
Sham injection at baseline and 4 weeks
Procedure: Focal/grid laser
Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.
Experimental: 0.5mg Ranibizumab plus laser
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
Intravitreal injection of 0.5 mg ranibizumab at baseline and 4 weeks
Other Name: Lucentis™
Procedure: Focal/grid laser
Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.
Active Comparator: 4-mg Triamcinolone Acetonide plus Laser
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
Intravitreal injection of 4 mg triamcinolone acetonide at baseline and sham injection at 4 weeks
Other Name: corticosteroid
Procedure: Focal/grid laser
Focal/grid laser for diabetic macular edema was performed 3 days to 10 days after the injection for all treatment groups.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

General Inclusion Criteria

  • Age >= 18 years
  • Diagnosis of diabetes mellitus (type 1 or type 2)
  • Fellow eye (if not a study eye) meets criteria.
  • Able and willing to provide informed consent. Study Eye Inclusion Criteria Subjects may have one or two study eyes. Subjects with two study eyes will be randomly assigned to receive sham injection at baseline and 4 weeks in one eye and either ranibizumab or triamcinolone in the other eye.
  • 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.

General 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).
  • 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.

Study Eye Exclusion Criteria, Study eye only:

  • 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).
  • History of treatment for DME at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).
  • 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 capsulotomy performed within 2 months prior to randomization.
  • Aphakia.
  • Intraocular pressure >= 25 mmHg.
  • History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: angle-closure glaucoma is not an exclusion criterion).
  • History of steroid-induced intraocular pressure elevation that required intraocular pressure-lowering treatment.
  • History of prior herpetic ocular infection.
  • Exam evidence of ocular toxoplasmosis.
  • Exam evidence of pseudoexfoliation.
  • Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

Fellow Eye Criteria

  • Intraocular pressure < 25 mmHg.
  • No history of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: angle-closure glaucoma is not an exclusion criterion).
  • No history of steroid-induced intraocular pressure elevation that required intraocular pressure-lowering treatment.
  • No exam evidence of pseudoexfoliation.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445003

  Show 56 Study Locations
Sponsors and Collaborators
Diabetic Retinopathy Clinical Research Network
Genentech, Inc.
Allergan
Investigators
Study Chair: Alexander J. Brucker, M.D. Scheie Eye Institute
Study Chair: Joseph Googe, Jr., M.D. Southeastern Retina Associates, P.C.
  More Information

No publications provided by Diabetic Retinopathy Clinical Research Network

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier: NCT00445003     History of Changes
Other Study ID Numbers: NEI-134, U10EY018817-03, U10EY014229-07, U10EY014231-09
Study First Received: March 6, 2007
Results First Received: April 14, 2011
Last Updated: January 30, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Diabetic Retinopathy Clinical Research Network:
Diabetic Retinopathy
Diabetic Macular Edema
Lucentis
Ranibizumab
Triamcinolone
Panretinal Photocoagulation
Combination Therapy
pdr

Additional relevant MeSH terms:
Diabetic Retinopathy
Macular Edema
Retinal Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Diabetic Angiopathies
Endocrine System Diseases
Eye Diseases
Macular Degeneration
Retinal Degeneration
Vascular Diseases
Triamcinolone
Triamcinolone Acetonide
Triamcinolone diacetate
Triamcinolone hexacetonide
Anti-Inflammatory Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014