Prompt Panretinal Photocoagulation Versus Ranibizumab+Deferred Panretinal Photocoagulation for Proliferative Diabetic Retinopathy
Condition: Proliferative Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy
Intervention: Prompt Panretinal Photocoagulation; 0.5-mg Ranibizumab; Deferred panretinal photocoagulation
Intervention description: Panretinal photocoagulation alone at baseline (full session completed within 56 days).; Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline and up to every 4 weeks using defined retreatment criteria.; PRP is deferred until failure/futility criteria for intravitreal injection are met.
Intervention MeSH terms: Ranibizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 305.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objective of the protocol is to determine if visual acuity outcomes at 2 years in
      eyes with proliferative diabetic retinopathy (PDR) that receive anti-vascular endothelial
      growth factor (anti-VEGF) therapy with deferred panretinal photocoagulation (PRP) are
      non-inferior to those in eyes that receive standard prompt PRP therapy.

      Secondary objectives include:

        -  Comparing other visual function outcomes (including Humphrey visual field testing and
           study participant self-reports of visual function) in eyes receiving anti-VEGF with
           deferred PRP with those in eyes receiving prompt PRP.

        -  Determining percent of eyes not requiring PRP when anti-VEGF is given in the absence of
           prompt PRP.

        -  Comparing safety outcomes between treatment groups.

        -  Comparing associated treatment and follow-up exam costs between treatment groups.
    

Eligibility criteria:

        Inclusion Criteria:

        Age >= 18 years -Individuals < 18 years old are not being included because proliferative
        diabetic retinopathy (PDR) is so rare in this age group that the diagnosis of PDR may be
        questionable.

        Diagnosis of diabetes mellitus (type 1 or type 2)

        Any one of the following will be considered to be sufficient evidence that diabetes is
        present:

          -  Current regular use of insulin for the treatment of diabetes

          -  Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes

          -  Documented diabetes by American Diabetes Association (ADA) and/or World Health
             Organization (WHO) criteria (see Procedures Manual for definitions) Able and willing
             to provide informed consent.

        Meets at least all of the following ocular criteria criteria:

          -  Presence of PDR which the investigator intends to manage with PRP alone but for which
             PRP can be deferred for at least 4 weeks in the setting of intravitreal ranibizumab,
             in the investigator's judgment.

          -  Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual
             acuity letter score > 24 (approximate Snellen equivalent 20/320) on the day of
             randomization.

          -  Media clarity, pupillary dilation, and study participant cooperation sufficient to
             administer PRP and obtain adequate fundus photographs and optical coherence tomography
             (OCT).

               -  Investigator must verify accuracy of OCT scan by ensuring it is centered and of
                  adequate quality

        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).

          -  Individuals in poor glycemic control who, within the last 4 months, initiated
             intensive insulin treatment (a pump or multiple daily injections) or plan to do so in
             the next 4 months should not be enrolled.

        Participation in an investigational trial within 30 days of randomization that involved
        treatment with any drug that has not received regulatory approval for the indication being
        studied.

          -  Study participants cannot receive another investigational drug while participating in
             the study.

        Known allergy to any component of the study drug.

        Blood pressure > 180/110 (systolic above 180 or diastolic above 110).

          -  If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual
             can become eligible.

        Myocardial infarction, other acute cardiac event requiring hospitalization, stroke,
        transient ischemic attack, or treatment for acute congestive heart failure within 4 months
        prior to randomization.

        Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

          -  These drugs should not be used during the study.

        For women of child-bearing potential: pregnant or lactating or intending to become pregnant
        within the next 3 years.

          -  Women who are potential study participants should be questioned about the potential
             for pregnancy. Investigator judgment is used to determine when a pregnancy test is
             needed.

        Individual is expecting to move out of the area of the clinical center to an area not
        covered by another Diabetic Retinopathy Clinical Research Network (DRCR.net) certified
        clinical center during the 3 years of the study.

        Individual has any of the following ocular characteristics:

          -  History of prior panretinal photocoagulation (prior PRP is defined as ≥ 100 burns
             outside of the posterior pole)

          -  Tractional retinal detachment involving the macula.

             -- A tractional retinal detachment is not an exclusion if it is outside of the
             posterior pole (not threatening the macula) and in the investigator's judgment, is not
             a contraindication to intravitreal ranibizumab treatment and also does not preclude
             deferring PRP for at least 4 weeks in the setting of intravitreal ranibizumab

          -  Exam evidence of neovascularization of the angle (neovascularization of the iris alone
             is not an exclusion if it does not preclude deferring PRP for at least 4 weeks in the
             investigator's judgment).

          -  If macular edema is present, it is considered to be primarily due to a cause other
             than diabetic macular edema.

             -- An eye should not be considered eligible if:

               -  macular edema is present that is considered to be related to ocular surgery such
                  as cataract extraction or

               -  clinical exam and/or OCT suggest that vitreoretinal interface abnormalities
                  disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary
                  cause of any macular edema.

          -  An ocular condition is present (other than diabetic retinopathy) that, in the opinion
             of the investigator, might 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.).

             -- A vitreous or preretinal hemorrhage is not an exclusion if it is out of the visual
             axis and in the investigator's judgment is not having any affect on visual acuity.

          -  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 were otherwise normal).

          -  History of intravitreal anti-VEGF treatment at any time in the past 2 months.

          -  History of corticosteroid treatment (intravitreal or peribulbar) at any time in the
             past 4 months.

             --If the investigator believes that there may still be a substantial effect 4 months
             after prior treatment (e.g., dose of intravitreal triamcinolone higher than 4 mg), the
             eye should not be included.

          -  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.

          -  Uncontrolled glaucoma (in investigator's judgment).

          -  Exam evidence of severe external ocular infection, including conjunctivitis,
             chalazion, or substantial blepharitis