Laser-Ranibizumab-Triamcinolone for Diabetic Macular Edema
Condition: Diabetic Retinopathy; Diabetic Macular Edema
MeSH terms: Macular Edema; Retinal Diseases; Diabetic Retinopathy; Edema
Intervention: Triamcinolone Acetonide + laser; Ranibizumab + laser; Sham injection + laser; Ranibizumab + deferred laser
Intervention description: 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.; 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.; 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.; 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.
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Ranibizumab; Triamcinolone diacetate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 691.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Diabetic Retinopathy; Diabetic Macular Edema; Lucentis; Ranibizumab; Triamcinolone; Laser photocoagulation; Combination Therapy

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.
    

Eligibility 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.