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Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial (MERIT)

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ClinicalTrials.gov Identifier: NCT02623426
Recruitment Status : Recruiting
First Posted : December 7, 2015
Last Update Posted : November 8, 2018
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
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 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.

Condition or disease Intervention/treatment Phase
Uveitis Macular Edema Drug: Dexamethasone intravitreal implant 0.7 mg Drug: Intravitreal Methotrexate 400 µg Drug: Intravitreal Ranibizumab 0.5 mg Phase 3

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 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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Macular Edema Ranibizumab v. Intravitreal Anti-inflammatory Therapy Trial
Actual Study Start Date : March 9, 2017
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema
Drug Information available for: Ranibizumab

Arm Intervention/treatment
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:

  1. 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.
  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
Standard preparation as described for intravitreal injections.
Other Name: Ozurdex

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.

Drug: 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.

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.

Drug: 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.
Other Name: Lucentis




Primary Outcome Measures :
  1. Percent change in central subfield thickness from the baseline OCT measurement [ Time Frame: At 12-week visit ]
    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.


Secondary Outcome Measures :
  1. IOP Elevation of >=24 mm Hg [ Time Frame: During 24 weeks of follow-up ]
    Rate of IOP elevation of >=24 mm Hg during follow-u

  2. IOP Elevation of >=30 mm Hg [ Time Frame: During 24 weeks of follow-up ]
    Rate of IOP elevation of >=30 mm Hg during follow-up

  3. IOP Elevation of >=10 mm Hg From Baseline [ Time Frame: During 24 weeks of follow-up ]
    Rate of IOP elevation of >=10 mm Hg from baseline

  4. Change in Macular Thickness as Measured by OCT [ Time Frame: Over 24 weeks of follow-up ]
    Percent change in macular thickness as measured by OCT

  5. >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction [ Time Frame: Over 24 weeks of follow-up ]
    Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction)

  6. Resolution of macular edema [ Time Frame: Over 24 weeks of follow-up ]
    Proportion of eyes with resolution of macular edema defined as normalization of the macular thickness, i.e., <260 um on the standard scale

  7. Change in Best-corrected Visual Acuity [ Time Frame: Over 24 weeks of follow-up ]
    Mean change in best-corrected visual acuity

  8. Vitreous Hemorrhage [ Time Frame: During 24 weeks of follow-up ]
    Count of vitreous hemorrhage as an immediate complication of injection

  9. Retinal Tear/Detachment [ Time Frame: During 24 weeks of follow-up ]
    Count of retinal tears/detachments

  10. Endophthalmitis [ Time Frame: During 24 weeks of follow-up ]
    Occurrence of endophthalmitis

  11. Severe vision loss [ Time Frame: During 24 weeks of follow-up ]
    Severe vision loss (>= 15 standard letters)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02623426


Contacts
Contact: Janet T Holbrook, PhD, MPH 443-287-5791 jholbro1@jhu.edu
Contact: Elizabeth A Sugar, PhD esugar2@jhu.edu

  Show 23 Study Locations
Sponsors and Collaborators
JHSPH Center for Clinical Trials
National Eye Institute (NEI)
Investigators
Study Chair: Douglas A Jabs, MD, MBA Icahn School of Medicine, Mount Sinai, New York, NY

Responsible Party: JHSPH Center for Clinical Trials
ClinicalTrials.gov Identifier: NCT02623426     History of Changes
Other Study ID Numbers: 119247
U10EY024527 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2015    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by JHSPH Center for Clinical Trials:
uveitic macular edema
uveitis

Additional relevant MeSH terms:
Edema
Macular Edema
Uveitis
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Uveal Diseases
Dexamethasone acetate
Dexamethasone
Anti-Inflammatory Agents
Methotrexate
Ranibizumab
BB 1101
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Abortifacient Agents, Nonsteroidal
Abortifacient Agents