A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)
Condition: Diabetic Retinopathy
MeSH terms: Macular Edema; Diabetic Retinopathy
Intervention: Laser Photocoagulation; Bevacizumab; Bevacizumab; Bevacizumab; Bevacizumab
Intervention description: Laser photocoagulation at baseline; If edema present at 12 weeks, can be treated with 2 intravitreal injections of 1.25 mg bevacizumab spaced 6 weeks apart; 1.25 mg intravitreal injection of bevacizumab at baseline and 6 weeks; 2.5 mg intravitreal injection of bevacizumab at baseline and 6 weeks; 1.25 mg intravitreal injection of bevacizumab at baseline (sham injection at 6 weeks); 1.25 mg intravitreal injection of bevacizumab at baseline, laser photocoagulation at 3 weeks, and intravitreal injection of 1.25 mg bevacizumab at 6 weeks
Intervention MeSH terms: Bevacizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 121.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetic; macular; edema; avastin; bevacizumab; anti-VEGF; retinal thickness; visual acuity; DME

Summary:

      This study will provide preliminary data on the dose and dose interval related effects of
      intravitreally administered Avastin on retinal thickness and visual acuity in subjects with
      Diabetic Macular Edema (DME) to aid in planning a phase 3 trial.

      In addition, this study will provide preliminary data on the safety of intravitreally
      administered Avastin in subjects with DME.
    

Eligibility criteria:

        SUBJECT-LEVEL INCLUSION CRITERIA

        To be eligible, the following inclusion criteria (1-3) must be met:

          1. Age >= 18 years

          2. Diagnosis of diabetes mellitus (type 1 or type 2)

          3. Able and willing to provide informed consent.

             EXCLUSION

             A subject is not eligible if any of the following exclusion criteria (4-13) are
             present:

          4. Significant renal disease, defined as a history of chronic renal failure requiring
             dialysis or kidney transplant.

          5. 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).

          6. 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.

          7. Known allergy to any component of the study drug.

          8. Blood pressure > 180/110 (systolic above 180 OR diastolic above 110).

          9. Major surgery within 28 days prior to randomization or major surgery planned during
             the next 6 months.

         10. Myocardial infarction, other cardiac event requiring hospitalization, stroke,
             transient ischemic attack, or treatment for acute congestive heart failure within 6
             months prior to randomization.

         11. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization.

         12. For women of child-bearing potential: pregnant or lactating or intending to become
             pregnant within the next 6 months.

         13. 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 6 months of the study.

        STUDY EYE CRITERIA

        The subject must have one eye meeting all of the inclusion criteria (a-e) and none of the
        exclusion criteria (f-r) listed below.

        Subjects can have only one study eye. If both eyes are eligible, the study eye will be
        selected by the investigator and subject.

        The eligibility criteria for a study eye are as follows:

        INCLUSION

          1. Best corrected E-ETDRS visual acuity letter score of >= 24 (i.e., 20/320 or better)
             and <= 78 (i.e., 20/32 or worse) within 8 days of randomization.

          2. On clinical exam, definite retinal thickening due to diabetic macular edema involving
             the center of the macula.

          3. OCT central subfield >=275 microns within 8 days of randomization.

          4. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate
             fundus photographs.

          5. If prior macular photocoagulation has been performed, the investigator believes that
             the study eye may possibly benefit from additional photocoagulation.

             EXCLUSION

             The following exclusions apply to the study eye only (i.e., they may be present for
             the nonstudy eye):

          6. Macular edema is considered to be due to a cause other than diabetic macular edema.

          7. An ocular condition is present such that, in the opinion of the investigator, visual
             acuity would not improve from resolution of macular edema (e.g., foveal atrophy,
             pigmentary changes, dense subfoveal hard exudates, nonretinal condition).

          8. 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, Irvine-Gass Syndrome, etc.).

          9. 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).

         10. History of treatment for DME at any time in the past 3 months (such as focal/grid
             macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs,
             or any other treatment).

         11. History of panretinal scatter photocoagulation (PRP) within 4 months prior to
             randomization.

         12. Anticipated need for PRP in the 6 months following randomization.

         13. History of prior pars plana vitrectomy.

         14. History of major ocular surgery (including cataract extraction, scleral buckle, any
             intraocular surgery, etc.) within prior 6 months or anticipated within the next 6
             months following randomization.

         15. History of YAG capsulotomy performed within 2 months prior to randomization.

         16. Aphakia.

         17. Uncontrolled glaucoma (in investigator's judgment).

         18. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or
             significant blepharitis.

        FELLOW EYE CRITERIA

        The fellow eye must meet the following criteria:

          1. Best corrected E-ETDRS visual acuity letter score >= 19 (i.e., 20/400 or better).

          2. No anti-VEGF treatment within the past 3 months and no expectation of such treatment
             in next 3 months.