Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema (LRT for DME)

This study has been completed.
Sponsor:
Collaborators:
Allergan
Genentech
Information provided by (Responsible Party):
Diabetic Retinopathy Clinical Research Network
ClinicalTrials.gov Identifier:
NCT00444600
First received: March 6, 2007
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Diabetic Retinopathy
Diabetic Macular Edema
Drug: Triamcinolone Acetonide + laser
Drug: Ranibizumab + laser
Drug: Sham injection + laser
Drug: Ranibizumab + deferred 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 in Combination With Laser Photocoagulation for Diabetic Macular Edema

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Mean Change in Visual Acuity (Letters) From Baseline to 1 Year Adjusted for Baseline Visual Acuity [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.

  • Distribution of Change in Visual Acuity (Letters) From Baseline to 1 Year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.

  • Change in Visual Acuity From Baseline to 1 Year Among Eyes That Were Pseudophakic at Baseline [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
  • Change in Visual Acuity From Baseline to 1 Year Among Eyes That Had Prior Treatment for Diabetic Macular Edema [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
  • Change in Visual Acuity From Baseline to 1 Year Grouped by Baseline Visual Acuity Letter Score [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.

  • Change in Visual Acuity From Baseline to 1 Year Grouped by Optical Coherence Tomography Central Subfield Thickness [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.

  • Change in Visual Acuity From Baseline to 1 Year Grouped by Diabetic Retinopathy Severity [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.

  • Change in Visual Acuity From Baseline to 1 Year Grouped by Diffuse vs. Focal Edema as Characterized by the Investigator [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in Retinal Thickening of Central Subfield on Optical Coherence Tomography From Baseline to 1 Year [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
    Negative change denotes an improvement.

  • Number of Injections in First Year [ Time Frame: from baseline to 1 year ] [ Designated as safety issue: No ]
    Maximum possible number of injections for each of the following groups: sham+prompt laser=13 sham injections;ranibizumab+prompt laser=13 ranibizumab injections; ranibizumab+deferred laser=13 ranibizumab injections; triamcinolone+prompt laser=4 triamcinolone injections and 9 sham injections.

  • Number of Laser Treatments Received Prior to the 1 Year Visit [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    One eye in the sham+prompt laser group did not receive laser until post 1-year due to an adverse event unrelated to study treatment. One eye in the triamcinolone+prompt laser did not receive laser until after 1-year due to missing 2 consecutive visits at the time of required laser treatment.

  • Percentage of Eyes Receiving Laser at the 48 Week Visit (%) [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Mean Optical Coherence Tomography Retinal Volume at 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Mean Change in Optical Coherence Tomography Retinal Volume From Baseline to 1 Year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Central Subfield Thickness < 250 With at Least a 25 Micron Decrease From Baseline to 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Distribution of Logarithmic Transformation of Optical Coherence Tomography (LogOCT) Improvement and Worsening [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Logarithmic transformation of optical coherence tomography central subfield thickness is calculated by taking the log base 10 of the ratio of the central subfield thickness divided by 200 and rounding to the nearest hundredth. The change is the change in the log values.

  • Eyes With Alternative Treatments Prior to the 1-year Visit [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Each combination of treatment only counted once.

  • Change From Moderately Severe Non-proliferative Diabetic Retinopathy or Better From Baseline to 1-year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    113 eyes had missing or ungradable photos at 1 year. Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833

  • Change From Severe Non-proliferative Diabetic Retinopathy or Worse From Baseline to 1-year [ Time Frame: from baseline to 1 Year ] [ Designated as safety issue: No ]
    Criteria are based on the ETDRS fundus photographic risk factors for the progression of diabetic retinopathy. ETDRS report no. 12. Ophthalmology 1991; 98:823-833, ETDRS Severity Scale = Diabetic retinopathy absent, minimal non-proliferative diabetic retinopathy (PDR), mild to moderately severe non-PDR, severe non-PDR, scars of full pr partial panretinal photocoagulation present PDR absent, mild to moderate PDR, high risk PDR, cannot grade, missing.

  • Cardiovascular Events According to Antiplatelet Trialists' Collaboration Through 1 Year [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Antiplatelet Trialists' Collaboration is a collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. MBJ 1994; 308:81-106. Nonfatal cerebrovascular accident includes ischemic or hemorrhagic or unknown events. Vascular death includes death from any potential vascular or unknown cause.

  • Major Ocular Adverse Events During First Year of Follow-Up [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Enrollment: 691
Study Start Date: March 2007
Study Completion Date: February 2014
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 0.5mg Ranibizumab plus laser Drug: Ranibizumab + laser
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.
Other Name: Lucentis, anti-VEGF drug
Experimental: 0.5 mg Ranibizumab plus deferred laser Drug: Ranibizumab + deferred laser
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.
Other Name: Lucentis, anti-VEGF drug
Experimental: 4 mg Triamcinolone plus laser Drug: Triamcinolone Acetonide + laser
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.
Other Name: corticosteroid
Active Comparator: Sham plus laser Drug: Sham injection + laser
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.
Other Name: placebo

  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

To be eligible, the following inclusion criteria (1-5) must be met:

  • 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

General Exclusion Criteria

A subject is not eligible if any of the following exclusion criteria are present:

  • 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.

Study Eye Inclusion Criteria

The subject must have one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below. A subject may have two study eyes only if both are eligible at the time of randomization.

  • 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.

Study Eye Exclusion Criteria

The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

  • 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, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal 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., vein 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 diabetic macular edema 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 panretinal (scatter) photocoagulation (PRP) within 4 months prior to randomization.
  • Anticipated need for PRP in the 6 months following randomization.
  • 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.
  • Intraocular pressure >= 25 mmHg.
  • History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: history of angle-closure glaucoma is not an exclusion criterion).
  • History of steroid-induced intraocular pressure (IOP) elevation that required IOP-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.
  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: NCT00444600

  Show 50 Study Locations
Sponsors and Collaborators
Diabetic Retinopathy Clinical Research Network
Allergan
Genentech
Investigators
Study Chair: Michael J. Elman, M.D. Elman Retina Group, PA
  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: NCT00444600     History of Changes
Other Study ID Numbers: NEI-133, U10EY018817-03, U10EY014229-07, U10EY014231-09
Study First Received: March 6, 2007
Results First Received: January 14, 2011
Last Updated: April 7, 2014
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
Laser photocoagulation
Combination Therapy

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

ClinicalTrials.gov processed this record on August 28, 2014