Macular Edema Nepafenac vs. Difluprednate Uveitis Trial (MEND)

January 11, 2021 updated by: University of California, San Francisco

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Tamil Nadu
      • Coimbatore, Tamil Nadu, India
        • Aravind Eye Hospital
      • Madurai, Tamil Nadu, India
        • Aravind Eye Hospital
      • Pondicherry, Tamil Nadu, India
        • Aravind Eye Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • Nevanac
Drug: Prednisolone acetate
prednisolone acetate 1% - corticosteroid eyedrop
Other Names:
  • 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 Names:
  • Durezol
Drug: Nepafenac
Nepafenac 0.1% - NSAID eyedrop
Other Names:
  • Nevanac

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central subfield thickness
Time Frame: 4 weeks
Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness
4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resolution
Time Frame: 4 weeks
proportion of patients with resolution of macular edema
4 weeks
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
4 weeks
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 weeks
Intraocular pressure (IOP) increase
Time Frame: 4 weeks
number of patients with intraocular pressure increase at least 10mmHg over baseline
4 weeks
High IOP
Time Frame: 4 weeks
Number of patients experiencing high intraocular pressure (> 24 mmHg)
4 weeks
Visual acuity
Time Frame: 4 weeks
best-corrected visual acuity (ETDRS protocol)
4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Aravind Eye Hospitals, India

Investigators

  • Principal Investigator: Nisha Acharya, MD MS, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 12, 2018

Primary Completion (Actual)

March 31, 2020

Study Completion (Actual)

March 31, 2020

Study Registration Dates

First Submitted

September 6, 2013

First Submitted That Met QC Criteria

September 6, 2013

First Posted (Estimate)

September 11, 2013

Study Record Updates

Last Update Posted (Actual)

January 13, 2021

Last Update Submitted That Met QC Criteria

January 11, 2021

Last Verified

January 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 18-24978

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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