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Macular Edema Nepafenac vs. Difluprednate Uveitis Trial (MEND)

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ClinicalTrials.gov Identifier: NCT01939691
Recruitment Status : Recruiting
First Posted : September 11, 2013
Last Update Posted : October 11, 2018
Sponsor:
Collaborator:
Aravind Eye Hospitals, India
Information provided by (Responsible Party):
University of California, San Francisco

Brief Summary:

Macular edema is a condition in which there is swelling in the macula, the part of the retina that gives you your best vision. This swelling can cause your vision to decline. When diagnosed early and treated, you vision usually can be preserved. However, if the swelling goes untreated for a long time, it can cause permanent vision loss.

We think that the three eye drop regimens in this study, difluprednate, difluprednate plus nepafenac, and prednisolone acetate plus nepafenac, might be effective in treating uveitic macular edema. Patients who enter this study are randomized to one of the three regimens and followed for 24 weeks.


Condition or disease Intervention/treatment Phase
Uveitis Macular Edema Drug: Difluprednate Drug: Nepafenac Drug: Prednisolone acetate Phase 4

Detailed Description:

Trial: Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial

Stratification: Systemic corticosteroid/immunosuppressive therapy vs. none

Treatments: 1) difluprednate 0.05% 2) combination therapy of prednisolone acetate 1% with nepafenac 0.1% 3) combination therapy of difluprednate 0.05% with nepafenac 0.1%

Masking: Unmasked treatment administration; masked outcome assessment (evaluation of OCT and visual acuity)

Follow-up: 2, 4, 6, 8, and 24 weeks

Treatment protocol:

Patients will be randomized at enrollment to either:

  • difluprednate 0.05% 4 drops per day
  • prednisolone acetate 1% 4 drops per day and nepafenac 0.1% 3 drops per day
  • difluprednate 0.05% 4 drops per day and nepafenac 0.1% 3 drops per day

If macular edema has not resolved at Week 4, continue study treatment at the same dose until Week 6.

If macular edema has resolved at Week 4, reduce study treatment as follows:

  • difluprednate 0.05% 1 drop per day until Week 6, then stop
  • prednisolone acetate 1% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 6, then stop
  • difluprednate 0.05% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 6, then stop

If macular edema does not resolve at Week 4 but has resolved at Week 6, reduce study treatment at Week 6 as follows:

  • difluprednate 0.05% 1 drop per day until Week 8, then stop
  • prednisolone acetate 1% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 8, then stop
  • difluprednate 0.05% 1 drop per day and nepafenac 0.1% 3 drops per day until Week 8, then stop If macular edema resolves at Week 4 but reoccurs at Week 6, treat per best medical judgement.

After Week 8, there are no restrictions on the treatments patients may receive, and medications can be tapered further, discontinued, or changed at the discretion of the treating physician and patient preference. If a patient with previously resolved macular edema has a recurrence, the physician may treat according to best medical judgement.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial
Masking: Single (Outcomes Assessor)
Masking Description: Masked outcome assessment (evaluation of OCT and visual acuity)
Primary Purpose: Treatment
Official Title: Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
Actual Study Start Date : September 12, 2018
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Experimental: Difluprednate
Difluprednate 0.05% ophthalmic emulsion 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at 4 weeks, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until 6 weeks and then decrease to 1 drop per day until Week 8 if resolved, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement.
Drug: Difluprednate
Difluprednate 0.05% - corticosteroid eyedrop
Other Name: Durezol

Experimental: Nepafenac plus Prednisolone acetate
Nepafenac 0.1% 3 times a day until resolution; prednisolone acetate 1% 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at Week 4, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until Week 6, then decrease to 1 drop per day until Week 8, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement.
Drug: Nepafenac
Nepafenac 0.1% - NSAID eyedrop
Other Name: Nevanac

Drug: Prednisolone acetate
prednisolone acetate 1% - corticosteroid eyedrop
Other Name: Pred Forte, Econo Pred

Experimental: Difluprednate plus Nepafenac
Nepafenac 0.1% 3 times a day until resolution; Difluprednate 0.05% ophthalmic emulsion 4 times a day until Week 4, then decrease according to protocol (if resolution of edema at 4 weeks, decrease to 1 drop per day until Week 6, then stop; if not resolved, continue at 4 times a day until 6 weeks and then decrease to 1 drop per day until Week 8 if resolved, then stop). If macular edema not resolved (or reoccurs) by Week 8, treat per best medical judgement.
Drug: Difluprednate
Difluprednate 0.05% - corticosteroid eyedrop
Other Name: Durezol

Drug: Nepafenac
Nepafenac 0.1% - NSAID eyedrop
Other Name: Nevanac




Primary Outcome Measures :
  1. Central subfield thickness [ Time Frame: 4 weeks ]
    Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness


Secondary Outcome Measures :
  1. Resolution [ Time Frame: 4 weeks ]
    proportion of patients with resolution of macular edema

  2. Improvement [ Time Frame: 4 weeks ]
    proportion of patients with improvement in macular edema defined as 20% or greater reduction in central subfield thickness by OCT or resolution of edema

  3. recurrence [ Time Frame: 4 weeks ]
    proportion of patients with recurrence of macular edema defined as greater than 20% increase in central subfield thickness to a value >320 microns by OCT or presence of cysts in an eye that previously had resolution of macular edema

  4. Intraocular pressure (IOP) increase [ Time Frame: 4 weeks ]
    number of patients with intraocular pressure increase at least 10mmHg over baseline

  5. High IOP [ Time Frame: 4 weeks ]
    Number of patients experiencing high intraocular pressure (> 24 mmHg)

  6. Visual acuity [ Time Frame: 4 weeks ]
    best-corrected visual acuity (ETDRS protocol)



Information from the National Library of Medicine

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

108 patients with uveitic ME will be enrolled at Aravind Eye Hospital in Madurai, India based on the following eligibility criteria:

Patient-level Inclusion criteria:

  • ≥18 years of age
  • Diagnosis of anterior, intermediate, posterior, or panuveitis (can be infectious or non-infectious)
  • Inactive or minimally active inflammation according to Standardization of Uveitis Nomenclature criteria (≤ 0.5+ Anterior Chamber (AC) cells, ≤ 0.5+ vitreous haze and no active retinal/choroidal lesions)
  • If on oral corticosteroids, a stable dose of <10 mg prednisone/day for >4 weeks
  • If on systemic corticosteroid-sparing immunomodulatory therapy, a stable dose for >4 weeks
  • If using prednisolone acetate 1% drops, stable regimen of ≤2 drops per day for >4 weeks
  • If infectious uveitis, inflammation must be inactive or minimally active per definition above and on stable dose of treatment for ≥4 weeks with no anticipated changes to treatment during the trial

Eye-level Inclusion Criteria

  • ME defined as thickening of the 1mm central subfield of the macula greater than 2 standard deviations above normal thickness (>320 µm by Heidelberg spectral-domain OCT) with or without the presence of intraretinal cysts.
  • Baseline intraocular pressure >5 mmHg and <21 mmHg (current use ≤3 intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable)
  • Media clarity and pupillary dilation sufficient to allow OCT testing and retinal photography
  • Best-corrected visual acuity of 5/200 or better

Patient-level Exclusion Criteria

  • Use of oral acetazolamide or other systemic carbonic anhydrase inhibitors at baseline
  • Known allergy or hypersensitivity to any component of the study drugs
  • Women who are pregnant or breastfeeding (pregnancy test should be administered prior to baseline fluorescein angiogram)
  • Patients unwilling or unable to not wear contact lenses during the study period
  • History of central serous chorioretinopathy in either eye

Eye-level Exclusion Criteria

  • Intravitreal or periocular corticosteroid injection in the past 8 weeks, dexamethasone implant in the past 12 months, or a fluocinolone acetonide implant in the past 3 years
  • Presence of an epiretinal membrane—noted clinically or by OCT—in the study eye, thought to be significant enough to preclude improvement of ME
  • Previous pars plana vitrectomy
  • History of severe glaucoma (C/D ratio > 0.9 or any notching of optic nerve to rim)
  • Prior use of difluprednate or nepafenac in the past 4 weeks

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): NCT01939691


Contacts
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Contact: Nisha Acharya, MD MS 415-476-8131 nisha.acharya@ucsf.edu

Locations
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India
Aravind Eye Hospital Recruiting
Madurai, Tamil Nadu, India
Contact: S.R. Rathinam         
Principal Investigator: S.R. Rathinam, FAMS, PhD         
Sub-Investigator: G. Vedhanayaki, DO         
Sponsors and Collaborators
University of California, San Francisco
Aravind Eye Hospitals, India
Investigators
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Principal Investigator: Nisha Acharya, MD MS University of California, San Francisco

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Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01939691     History of Changes
Other Study ID Numbers: 18-24978
First Posted: September 11, 2013    Key Record Dates
Last Update Posted: October 11, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by University of California, San Francisco:
difluprednate
prednisolone acetate
nepafenac

Additional relevant MeSH terms:
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Macular Edema
Uveitis
Edema
Signs and Symptoms
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Uveal Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Nepafenac
Fluprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Difluprednate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents