Clinical trial NCT02623426: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Official title: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Uveitis
Macular Edema
Keywords: uveitic macular edema
uveitis
Lead sponsor: JHSPH Center for Clinical Trials
Sponsor class: OTHER
Collaborators: name: National Eye Institute (NEI)
First posted: 2015-12-07
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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 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.

Primary outcomes:
measure: Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks
timeFrame: At 12-week visit
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jules Stein Eye Institute, UCLA
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Miami
country: United States
facility: Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Ophthalmic Consultants of Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: Kellogg Eye Center, University of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke Eye Center, Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: Scheie Eye Institute, University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: MidAtlanitc Retina, Wills Eye Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: Retinal Consultants of Houston
state: Texas
city: Salt Lake City
country: United States
facility: John A. Moran Eye Center, University of Utah
state: Utah
city: East Melbourne
country: Australia
facility: Royal Victorian Eye and Ear Hospital
state: Victoria
city: Montreal
country: Canada
facility: McGill University
state: Quebec
city: Bhubaneswar
country: India
facility: LV Prasad Eye Institute - Bhubaneswar
state: Odisha
city: Chennai
country: India
facility: Medical and Vision Research Foundation
state: Tamil Nadu
city: Hyderabad
country: India
facility: LV Prasad Eye Institute - Hyderabad
state: Telangana
city: Chandigarh
country: India
facility: Advanced Eye Center, Post Graduate Institute of Medical Education and Research
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust
state: England
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
state: England
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Trust
state: England
city: Liverpool
country: United Kingdom
facility: Liverpool University Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Moorfields Eye Hospital NHS Foundation Trust
state: England
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: London
country: United Kingdom
facility: Moorfields Eye Hospital
Study officials:
affiliation: Center for Clinical Trials and Evidence Synthesis, JHU, Baltimore, MD
name: Douglas A Jabs, MD, MBA
role: STUDY_CHAIR
References: