Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

Phase 3

Completed

• Conditions: Uveitis; Macular Edema
• Interventions: Drug: Dexamethasone intravitreal implant 0.7 mg; Drug: Intravitreal Methotrexate 400 µg; Drug: Intravitreal Ranibizumab 0.5 mg

• Registration Number: NCT02623426
• Lead Sponsor: JHSPH Center for Clinical Trials

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.

Study Timeline

• Study First Submitted: 2015-12-03
• Study First Submitted QC: 2015-12-04
• Study First Posted: 2015-12-07
• Study Start: 2017-03-09
• Primary Completion: 2021-10-27
• Study Completion: 2022-02-02
• Results First Submitted: 2023-04-06
• Status Verified: 2023-06
• Results First Submitted QC: 2023-06-20
• Last Update Submitted: 2023-06-20
• Results First Posted: 2023-07-10
• Last Update Posted: 2023-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 194

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexamethasone intravitreal implant 0.7mg	Dexamethasone intravitreal implant 0.7 mg	Participants were randomized to a treatment group. A participant may have 1 or 2 eyes with macular edema (eligible eyes) receiving the same treatment. 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: 1. Central subfield thickness greater than 1.1X upper limit of normal (330 μm for Zeiss and Topcon Spectral Domain (SD) Optical Coherence Tomography (OCT) and 352 μm for Heidelberg OCT) and/or cystoid space(s) within 1 mm central subfield. 2. 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	Intravitreal Methotrexate 400 µg	Participants were randomized to a treatment group. A participant may have 1 or 2 eyes with macular edema (eligible eyes) receiving the same treatment. 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	Intravitreal Ranibizumab 0.5 mg	Participants were randomized to a treatment group. A participant may have 1 or 2 eyes with macular edema (eligible eyes) receiving the same treatment. 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.

Primary Outcome Measures

Name	Time	Method
Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks	At 12-week visit	The primary outcome is the change in central subfield thickness from baseline to 12 weeks measured on a relative scale as the the proportion of the baseline central subfield thickness. The proportion of baseline subfield thickness is estimated by a mixed effect model that includes time points for baseline, week 4, week 8, and week 12 and the treatment group. The treatment effect is the interaction (product) of time point and treatment. Contrasts of the model parameter estimates were used to calculate the change from baseline to week 12 and the comparison between treatment groups.; Values less than 1 indicate a decrease in retinal thickness with lower values indicating greater decreases (improvement).The OCT outcomes were measured by masked readers. The 12-week visit was chosen as the time to assess the primary outcome because of the ranibizumab treatment schedule and the peak effect time for dexamethasone

Trial Locations

Locations (33)

Moorfields Eye Hospital NHS Foundation Trust; 🇬🇧 London, England, United Kingdom

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

Medical and Vision Research Foundation; 🇮🇳 Chennai, Tamil Nadu, India

University Hospitals Birmingham NHS Foundation Trust; 🇬🇧 Birmingham, United Kingdom

Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine; 🇺🇸 Miami, Florida, United States

Jules Stein Eye Institute, UCLA; 🇺🇸 Los Angeles, California, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Kellogg Eye Center, University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Massachusetts Eye and Ear Infirmary; 🇺🇸 Boston, Massachusetts, United States

Ophthalmic Consultants of Boston; 🇺🇸 Boston, Massachusetts, United States

MidAtlanitc Retina, Wills Eye Hospital; 🇺🇸 Philadelphia, Pennsylvania, United States

Johns Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Scheie Eye Institute, University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Retinal Consultants of Houston; 🇺🇸 Houston, Texas, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

John A. Moran Eye Center, University of Utah; 🇺🇸 Salt Lake City, Utah, United States

McGill University; 🇨🇦 Montreal, Quebec, Canada

Royal Victorian Eye and Ear Hospital; 🇦🇺 East Melbourne, Victoria, Australia

Advanced Eye Center, Post Graduate Institute of Medical Education and Research; 🇮🇳 Chandigarh, India

University Hospitals Bristol NHS Foundation Trust; 🇬🇧 Bristol, England, United Kingdom

LV Prasad Eye Institute - Hyderabad; 🇮🇳 Hyderabad, Telangana, India

LV Prasad Eye Institute - Bhubaneswar; 🇮🇳 Bhubaneswar, Odisha, India

Cambridge University Hospitals NHS Foundation Trust; 🇬🇧 Cambridge, England, United Kingdom

University Hospitals of Leicester NHS Trust; 🇬🇧 Leicester, England, United Kingdom

Manchester University NHS Foundation Trust; 🇬🇧 Manchester, England, United Kingdom

Moorfields Eye Hospital; 🇬🇧 London, United Kingdom

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

Vanderbilt; 🇺🇸 Nashville, Tennessee, United States

Duke Eye Center, Duke University; 🇺🇸 Durham, North Carolina, United States

Liverpool University Hospitals NHS Foundation Trust; 🇬🇧 Liverpool, England, United Kingdom