Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

NCT02623426 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: 119247U10EY024527ML29257
• Study Type: interventional
• Target: 194
• Locations: 5 countries
• Sites: 33

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.

Conditions

Uveitis; Macular Edema

Keywords

uveitic macular edema; uveitis

Outcome Measures

Primary Outcomes (1)

• Proportion of Baseline Central Subfield Thickness Observed at 12 Weeks

  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

  At 12-week visit

Study Arms (3)

Dexamethasone intravitreal implant 0.7mg

ACTIVE COMPARATOR

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;

Drug: Dexamethasone intravitreal implant 0.7 mg

Intravitreal methotrexate 400µg in 0.1mL

ACTIVE COMPARATOR

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.

Drug: Intravitreal Methotrexate 400 µg

Intravitreal ranibizumab 0.5mg in 0.05mL

ACTIVE COMPARATOR

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.

Drug: Intravitreal Ranibizumab 0.5 mg

Interventions

Dexamethasone intravitreal implant 0.7 mg DRUG

Standard preparation as described for intravitreal injections.

Also known as: Ozurdex

Dexamethasone intravitreal implant 0.7mg

Intravitreal Methotrexate 400 µg DRUG

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 methotrexate 400µg in 0.1mL

Intravitreal Ranibizumab 0.5 mg DRUG

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.

Also known as: Lucentis

Intravitreal ranibizumab 0.5mg in 0.05mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older;
• 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;
• 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
• Baseline fluorescein angiogram that, as assessed by the study ophthalmologist, is gradable for degree of leakage in the central subfield;
• Best corrected visual acuity (BCVA) 5/200 or better;
• 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);
• Media clarity and pupillary dilation sufficient to allow OCT testing and assessment of the fundus.

You may not qualify if:

• History of infectious uveitis in either eye;
• History of keratitis (with the exception of keratitis due to dry eye) in either eye;
• History of central serous retinopathy in either eye;
• Active infectious conjunctivitis in either eye;
• 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);
• 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);
• Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;
• Known allergy or hypersensitivity to any component of the study drugs;
• 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;
• History of infectious endophthalmitis;
• 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);
• 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);
• 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);
• Torn or ruptured posterior lens capsule
• Presence of silicone oil;

Sponsors & Collaborators

• JHSPH Center for Clinical Trials: lead
• National Eye Institute (NEI): collaborator

Study Sites (33)

Jules Stein Eye Institute, UCLA

Los Angeles, California, 90095, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

Location

Ophthalmic Consultants of Boston

Boston, Massachusetts, 02114, United States

Location

Kellogg Eye Center, University of Michigan

Ann Arbor, Michigan, 48105, United States

Location

Duke Eye Center, Duke University

Durham, North Carolina, 27710, United States

Location

Scheie Eye Institute, University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MidAtlanitc Retina, Wills Eye Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Retinal Consultants of Houston

Houston, Texas, 77030, United States

Location

John A. Moran Eye Center, University of Utah

Salt Lake City, Utah, 84132, United States

Location

Royal Victorian Eye and Ear Hospital

East Melbourne, Victoria, Australia

Location

McGill University

Montreal, Quebec, H4A 3S5, Canada

Location

LV Prasad Eye Institute - Bhubaneswar

Bhubaneswar, Odisha, India

Location

Medical and Vision Research Foundation

Chennai, Tamil Nadu, India

Location

LV Prasad Eye Institute - Hyderabad

Hyderabad, Telangana, 500034, India

Location

Advanced Eye Center, Post Graduate Institute of Medical Education and Research

Chandigarh, India

Location

University Hospitals Bristol NHS Foundation Trust

Bristol, England, BS1 2LX, United Kingdom

Location

Cambridge University Hospitals NHS Foundation Trust

Cambridge, England, CB2 0QQ, United Kingdom

Location

University Hospitals of Leicester NHS Trust

Leicester, England, LE1 5WW, United Kingdom

Location

Liverpool University Hospitals NHS Foundation Trust

Liverpool, England, L7 8XP, United Kingdom

Location

Moorfields Eye Hospital NHS Foundation Trust

London, England, EC1V 2PD, United Kingdom

Location

Manchester University NHS Foundation Trust

Manchester, England, M13 (WL, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B152WB, United Kingdom

Location

Moorfields Eye Hospital

London, EC1V 9EL, United Kingdom

Location

Related Publications (1)

• Multicenter Uveitis Steroid Treatment Trial (MUST) Research Group, Writing Committee:; Acharya NR, Vitale AT, Sugar EA, Holbrook JT, Burke AE, Thorne JE, Altaweel MM, Kempen JH, Jabs DA. Intravitreal Therapy for Uveitic Macular Edema-Ranibizumab versus Methotrexate versus the Dexamethasone Implant: The MERIT Trial Results. Ophthalmology. 2023 Sep;130(9):914-923. doi: 10.1016/j.ophtha.2023.04.011. Epub 2023 Jun 13.

  PMID: 37318415 DERIVED

MeSH Terms

Conditions

Uveitis; Macular Edema

Interventions

Dexamethasone; Calcium Dobesilate; Ranibizumab

Condition Hierarchy (Ancestors)

Uveal Diseases; Eye Diseases; Macular Degeneration; Retinal Degeneration; Retinal Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Douglas A Jabs, MD, MBA
• Organization: Johns Hopkins Bloomberg School of Public Health

djabs1@jhmi.edu

410 -955-1254

Study Officials

• Douglas A Jabs, MD, MBA

  Center for Clinical Trials and Evidence Synthesis, JHU, Baltimore, MD

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2015
• First Posted: December 7, 2015
• Study Start: March 9, 2017
• Primary Completion: October 27, 2021
• Study Completion: February 2, 2022
• Last Updated: July 10, 2023
• Results First Posted: July 10, 2023

Record last verified: 2023-06

Locations

CA (1); AU (1); IN (4); US (19); GB (8)