Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

Macular Edema Clinical Trial

— MERIT  

Official title:

Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02623426
• Other study ID #: 119247
• Secondary ID: U10EY024527ML292
• Status: Completed
• Phase: Phase 3
• Start date: March 9, 2017
• Est. completion date: February 2, 2022

Study information

• Verified date: June 2023
• Source: JHSPH Center for Clinical Trials
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 194
• Est. completion date: February 2, 2022
• Est. primary completion date: October 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Edema
• Macular Edema
• Uveitis

Intervention

Drug:
• Dexamethasone intravitreal implant 0.7 mg
Standard preparation as described for intravitreal injections.
• Intravitreal Methotrexate 400 µg
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
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.

Locations

Country	Name	City	State
Australia	Royal Victorian Eye and Ear Hospital	East Melbourne	Victoria
Canada	McGill University	Montreal	Quebec
India	LV Prasad Eye Institute - Bhubaneswar	Bhubaneswar	Odisha
India	Advanced Eye Center, Post Graduate Institute of Medical Education and Research	Chandigarh
India	Medical and Vision Research Foundation	Chennai	Tamil Nadu
India	LV Prasad Eye Institute - Hyderabad	Hyderabad	Telangana
United Kingdom	University Hospitals Birmingham NHS Foundation Trust	Birmingham
United Kingdom	University Hospitals Bristol NHS Foundation Trust	Bristol	England
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester	England
United Kingdom	Liverpool University Hospitals NHS Foundation Trust	Liverpool	England
United Kingdom	Moorfields Eye Hospital	London
United Kingdom	Moorfields Eye Hospital NHS Foundation Trust	London	England
United Kingdom	Manchester University NHS Foundation Trust	Manchester	England
United States	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston	Boston	Massachusetts
United States	Northwestern University	Chicago	Illinois
United States	Rush University Medical Center	Chicago	Illinois
United States	Duke Eye Center, Duke University	Durham	North Carolina
United States	Retinal Consultants of Houston	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	Jules Stein Eye Institute, UCLA	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine	Miami	Florida
United States	Vanderbilt	Nashville	Tennessee
United States	MidAtlanitc Retina, Wills Eye Hospital	Philadelphia	Pennsylvania
United States	Scheie Eye Institute, University of Pennsylvania	Philadelphia	Pennsylvania
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	University of California, San Francisco	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
JHSPH Center for Clinical Trials	National Eye Institute (NEI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  India,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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