Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
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 at the 6 month clinic visit. The primary outcome is percent change in central subfield thickness from the baseline OCT measurement to the 12 week visit.
- Macular Edema
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
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 SUN132 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 3DOCT 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.
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-VEGF agent, intravitreal methotrexate, or intravitreal/periocular corticosteroid administered in past 4 weeks; 19. Fluocinolone acetonide implant (Retisert) placed in past 3 years.
- Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Single (Outcomes Assessor)
Dexamethasone intravitreal implant 0.7mg
|Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at study visit M03 (8 weeks) if re-treatment criteria met. Retreatment permitted at later time points if retreatment criteria met. Re-treatment criteria: Central subfield thickness greater than 1.1X upper limit of normal (330 μm for Zeiss and Topcon SD OCT and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. IOP of <25 mm Hg (treatment with ≤3 IOP-lowering agents permitted) Minimum time between treatments: minimum target is 8 weeks after last injection but re-injection permitted as early as 51 days after last injection;||
Intravitreal methotrexate 400µg in 0.1mL
|Eligible eye(s) treated at study visit M01 (week 0). Retreatment required at M02 (4 weeks) and M03 (8 weeks) if retreatment criteria met. Retreatment permitted at later time points if retreatment criteria met. Minimum time between treatments: minimum target is 4 weeks after last injection but re-injection permitted as early as 23 days after last injection.||
Intravitreal ranibizumab 0.5mg in 0.05mL
|Eligible eye(s) treated at study visits M01 (week 0), M02 (4 weeks), and M03 (8 weeks). Retreatment permitted at M04 (12 weeks) and at later time points if retreatment criteria met. Minimum time between treatments: minimum target is 4 weeks after last injection but re-injection permitted as early as 23 days after last injection. Re-treatment permitted at later time points if re-treatment criteria met.||
- JHSPH Center for Clinical Trials
Study ContactJanet T Holbrook, PhD, MPH
Macular edema (ME) is the most common structural complication and cause of visual impairment and legal blindness in uveitis patients. Traditional approaches to the treatment of uveitic ME have included the use of regional corticosteroid therapy, delivered periocularly, including posterior sub-Tenon's and orbital floor injections, or via the intravitreal route. While corticosteroid injections may reduce ME and improve vision, the effect is often variable with a limited duration. Persistent macular edema is a common occurrence and often requires repeated intravitreal injections of corticosteroids, which expose eyes to a significant risk of increased intraocular pressure ocular and cataract development. The often refractory nature of uveitic ME and its impact on visual function underscores the need to identify effective alternative medical therapeutic options. Recent pilot studies have shown intravitreal methotrexate (MTX) and intravitreal ranibizumab (Lucentis®, Genentech Inc., San Francisco, CA) to be promising treatments for uveitic ME, and intravitreal dexamethasone implant (Ozurdex®, Allergan, Irvine, CA) has recently been approved by the U.S. FDA for uveitic ME in patients with non-infectious uveitis. In addition to being effective, intravitreal MTX and ranibizumab potentially may have less ocular side effects than corticosteroids, particularly less IOP elevation. However, the relative efficacy of these treatments is unknown. The Macular Edema Ranibizumab v. Intravitreal anti-inflammatory Therapy (MERIT) Trial will compare the relative efficacy and safety of intravitreal methotrexate, ranibizumab, and dexamethasone implant. MERIT is a parallel design (1:1:1), randomized comparative effectiveness trial with an anniversary close-out at the 6 month clinic visit. The primary outcome is percent change in central subfield thickness from the baseline OCT measurement to the 12 week visit.