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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02623426




Registration number
NCT02623426
Ethics application status
Date submitted
3/12/2015
Date registered
7/12/2015
Date last updated
25/03/2019

Titles & IDs
Public title
Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Scientific title
Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Secondary ID [1] 0 0
U10EY024527
Secondary ID [2] 0 0
119247
Universal Trial Number (UTN)
Trial acronym
MERIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Uveitis 0 0
Macular Edema 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Eye 0 0 0 0
Diseases / disorders of the eye
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dexamethasone intravitreal implant 0.7 mg
Treatment: Drugs - Intravitreal Methotrexate 400 µg
Treatment: Drugs - Intravitreal Ranibizumab 0.5 mg

Active Comparator: 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;

Active Comparator: 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.

Active Comparator: 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.


Treatment: Drugs: Dexamethasone intravitreal implant 0.7 mg
Standard preparation as described for intravitreal injections.

Treatment: Drugs: 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.

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percent change in central subfield thickness from the baseline OCT measurement - The primary outcome is the percent change in central subfield thickness from the baseline OCT measurement at the 12-week visit. The assessment of OCT outcomes will be performed by masked readers. The 12-week visit was chosen as the time to assess the primary outcome because the ranibizumab treatment arm specifies injections at baseline, 4 weeks and 8 weeks in all participants, and because the peak benefit for the dexamethasone pellet appears to be at the 8 to 12 weeks.
Timepoint [1] 0 0
At 12-week visit
Secondary outcome [1] 0 0
IOP Elevation of >=24 mm Hg - Rate of IOP elevation of >=24 mm Hg during follow-u
Timepoint [1] 0 0
During 24 weeks of follow-up
Secondary outcome [2] 0 0
IOP Elevation of >=30 mm Hg - Rate of IOP elevation of >=30 mm Hg during follow-up
Timepoint [2] 0 0
During 24 weeks of follow-up
Secondary outcome [3] 0 0
IOP Elevation of >=10 mm Hg From Baseline - Rate of IOP elevation of >=10 mm Hg from baseline
Timepoint [3] 0 0
During 24 weeks of follow-up
Secondary outcome [4] 0 0
Change in Macular Thickness as Measured by OCT - Percent change in macular thickness as measured by OCT
Timepoint [4] 0 0
Over 24 weeks of follow-up
Secondary outcome [5] 0 0
>= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction - Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction)
Timepoint [5] 0 0
Over 24 weeks of follow-up
Secondary outcome [6] 0 0
Resolution of macular edema - Proportion of eyes with resolution of macular edema defined as normalization of the macular thickness, i.e., <260 um on the standard scale
Timepoint [6] 0 0
Over 24 weeks of follow-up
Secondary outcome [7] 0 0
Change in Best-corrected Visual Acuity - Mean change in best-corrected visual acuity
Timepoint [7] 0 0
Over 24 weeks of follow-up
Secondary outcome [8] 0 0
Vitreous Hemorrhage - Count of vitreous hemorrhage as an immediate complication of injection
Timepoint [8] 0 0
During 24 weeks of follow-up
Secondary outcome [9] 0 0
Retinal Tear/Detachment - Count of retinal tears/detachments
Timepoint [9] 0 0
During 24 weeks of follow-up
Secondary outcome [10] 0 0
Endophthalmitis - Occurrence of endophthalmitis
Timepoint [10] 0 0
During 24 weeks of follow-up
Secondary outcome [11] 0 0
Severe vision loss - Severe vision loss (>= 15 standard letters)
Timepoint [11] 0 0
During 24 weeks of follow-up

Eligibility
Key inclusion 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 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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-VEGF agent, intravitreal methotrexate, or intravitreal/periocular corticosteroid
administered in past 4 weeks;

19. Fluocinolone acetonide implant (Retisert) placed in past 3 years.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Royal Victorian Eye and Ear Hospital - East Melbourne
Recruitment postcode(s) [1] 0 0
- East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
Canada
State/province [15] 0 0
Quebec
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Birmingham
Country [17] 0 0
United Kingdom
State/province [17] 0 0
London

Funding & Sponsors
Primary sponsor type
Other
Name
JHSPH Center for Clinical Trials
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Eye Institute (NEI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 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.
Trial website
https://clinicaltrials.gov/show/NCT02623426
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Douglas A Jabs, MD, MBA
Address 0 0
Icahn School of Medicine, Mount Sinai, New York, NY
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Janet T Holbrook, PhD, MPH
Address 0 0
Country 0 0
Phone 0 0
443-287-5791
Fax 0 0
Email 0 0
jholbro1@jhu.edu
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02623426