Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Condition: Uveitis; Macular Edema
MeSH terms: Macular Edema; Uveitis; Edema
Intervention: Dexamethasone intravitreal implant 0.7 mg; Intravitreal Methotrexate 400 µg; Intravitreal Ranibizumab 0.5 mg
Intervention description: Standard preparation as described for intravitreal injections.; Intravitreal Methotrexate 400 µg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection.; Intravitreal Ranibizumab 0.5 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to the injection.
Intervention MeSH terms: Dexamethasone; Methotrexate; Ranibizumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 194.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: uveitic macular edema; uveitis

Summary:

      The Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial will
      compare the relative efficacy and safety of intravitreal methotrexate, intravitreal
      ranibizumab, and the intravitreal dexamethasone implant for the treatment of uveitic macular
      edema persisting or reoccurring after an intravitreal corticosteroid injection. MERIT is a
      parallel design (1:1:1), randomized comparative trial with an anniversary close-out after 6
      months of follow-up. The primary outcome is percent change in central subfield thickness from
      the baseline OCT measurement to the 12 week visit.
    

Eligibility criteria:

        Inclusion criteria:

        Patient level inclusion criterion

          1. 18 years of age or older;

             Eye level inclusion criteria - at least one eye must meet all of the following
             conditions

          2. Inactive or minimally active non-infectious anterior, intermediate, posterior or
             panuveitis, as defined by the Standardization of Uveitis Nomenclature (SUN) Working
             Group criteria as ≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze grade and no
             active retinal/choroidal lesions for a minimum of 4 weeks;

          3. Macular edema (ME) defined as the presence of macular thickness greater than the
             normal range for the OCT machine being used (see cut points below), regardless of the
             presence of cysts, following an intravitreal corticosteroid injection (≥ 4 weeks
             following intravitreal triamcinolone injection or ≥ 12 weeks following intravitreal
             dexamethasone implant injection);

             Greater than 300 μm for Zeiss Cirrus Greater than 320 μm for Heidelberg Spectralis
             Greater than 300 μm for Topcon SD OCT

          4. Baseline fluorescein angiogram that, as assessed by the study ophthalmologist, is
             gradable for degree of leakage in the central subfield;

          5. Best corrected visual acuity (BCVA) 5/200 or better;

          6. Baseline intraocular pressure > 5 mm Hg and ≤ 21 mm Hg (current use of ≤3 intraocular
             pressure-lowering medications and/or prior glaucoma surgery are acceptable (Note:
             combination medications, e.g., Combigan, are counted as two IOP-lowering medications);

          7. Media clarity and pupillary dilation sufficient to allow OCT testing and assessment of
             the fundus.

        Exclusion criteria:

        Patient level exclusion criteria

          1. History of infectious uveitis in either eye;

          2. History of infectious scleritis of any type in either eye (Note: History of
             noninfectious scleritis that has been active in past 12 months is an eye-level
             exclusion -see #13 below);

          3. History of keratitis (with the exception of keratitis due to dry eye) in either eye;

          4. History of central serous retinopathy in either eye;

          5. Active infectious conjunctivitis in either eye;

          6. Oral prednisone dose > 10 mg per day (or of an alternative corticosteroid at a dose
             higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤ 10
             mg per day at baseline that has not been stable for at least 4 weeks (note: if patient
             is off of oral prednisone at baseline (M01 study visit) dose stability requirement for
             past 4 weeks does not apply);

          7. Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks
             (note: use of systemic methotrexate is acceptable as long as regimen has been stable
             for at least 4 weeks);

          8. Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;

          9. Known allergy or hypersensitivity to any component of the study drugs;

         10. For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy
             test; unwilling to practice an adequate birth control method (abstinence, combination
             barrier and spermicide, or hormonal) for duration of trial;

             Eye level exclusion criteria - at least one eye that meets all inclusion criteria
             cannot have any of the following conditions

         11. History of infectious endophthalmitis;

         12. History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥ 0.9
             or any notching of optic nerve to the rim);

         13. History of active noninfectious scleritis in past 12 months (Note: History of
             noninfectious scleritis is acceptable if the last episode of active scleritis resolved
             at least 12 months prior to enrollment);

         14. Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of
             study ophthalmologist may be significant enough to limit improvement of ME (i.e.,
             causing substantial wrinkling of the retinal surface);

         15. Torn or ruptured posterior lens capsule

         16. Presence of silicone oil;

         17. Ozurdex administered in past 12 weeks;

         18. Anti-vascular endothelial growth factor (VEGF) agent, intravitreal methotrexate, or
             intravitreal/periocular corticosteroid administered in past 4 weeks;

         19. Fluocinolone acetonide implant (Retisert) placed in past 3 years.