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Macular Edema Nepafenac vs. Difluprednate Uveitis Trial (MEND)

Primary Purpose

Uveitis, Macular Edema

Status

Terminated

Phase

Phase 4

Locations

India

Study Type

Interventional

Intervention

Difluprednate

Nepafenac

Prednisolone acetate

About this trial

This is an interventional treatment trial for Uveitis focused on measuring difluprednate, prednisolone acetate, nepafenac

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Aravind Eye Hospital
Aravind Eye Hospital
Aravind Eye Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Difluprednate

Nepafenac plus Prednisolone acetate

Difluprednate plus Nepafenac

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Central subfield thickness

Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness

Secondary Outcome Measures

Resolution

proportion of patients with resolution of macular edema

Improvement

proportion of patients with improvement in macular edema defined as 20% or greater reduction in central subfield thickness by OCT or resolution of edema

recurrence

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

Intraocular pressure (IOP) increase

number of patients with intraocular pressure increase at least 10mmHg over baseline

High IOP

Number of patients experiencing high intraocular pressure (> 24 mmHg)

Visual acuity

best-corrected visual acuity (ETDRS protocol)

Full Information

NCT ID

NCT01939691

First Posted

September 6, 2013

Last Updated

January 11, 2021

Sponsor

University of California, San Francisco

Collaborators

Aravind Eye Hospitals, India

1. Study Identification

Unique Protocol Identification Number

NCT01939691

Brief Title

Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Acronym

MEND

Official Title

Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Study Type

Interventional

2. Study Status

Record Verification Date

January 2021

Overall Recruitment Status

Terminated

Why Stopped

Difficulty enrolling

Study Start Date

September 12, 2018 (Actual)

Primary Completion Date

March 31, 2020 (Actual)

Study Completion Date

March 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of California, San Francisco

Collaborators

Aravind Eye Hospitals, India

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Uveitis, Macular Edema

Keywords

difluprednate, prednisolone acetate, nepafenac

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Model Description

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

Masking

Outcomes Assessor

Masking Description

Masked outcome assessment (evaluation of OCT and visual acuity)

Allocation

Randomized

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Difluprednate

Arm Type

Experimental

Arm Description

Arm Title

Nepafenac plus Prednisolone acetate

Arm Type

Experimental

Arm Description

Arm Title

Difluprednate plus Nepafenac

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Difluprednate

Other Intervention Name(s)

Durezol

Intervention Description

Difluprednate 0.05% - corticosteroid eyedrop

Intervention Type

Drug

Intervention Name(s)

Nepafenac

Other Intervention Name(s)

Nevanac

Intervention Description

Nepafenac 0.1% - NSAID eyedrop

Intervention Type

Drug

Intervention Name(s)

Prednisolone acetate

Other Intervention Name(s)

Pred Forte, Econo Pred

Intervention Description

prednisolone acetate 1% - corticosteroid eyedrop

Primary Outcome Measure Information:

Title

Central subfield thickness

Description

Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Resolution

Description

proportion of patients with resolution of macular edema

Time Frame

4 weeks

Title

Improvement

Description

proportion of patients with improvement in macular edema defined as 20% or greater reduction in central subfield thickness by OCT or resolution of edema

Time Frame

4 weeks

Title

recurrence

Description

Time Frame

4 weeks

Title

Intraocular pressure (IOP) increase

Description

number of patients with intraocular pressure increase at least 10mmHg over baseline

Time Frame

4 weeks

Title

High IOP

Description

Number of patients experiencing high intraocular pressure (> 24 mmHg)

Time Frame

4 weeks

Title

Visual acuity

Description

best-corrected visual acuity (ETDRS protocol)

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Nisha Acharya, MD MS

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

Aravind Eye Hospital

City

Coimbatore

State/Province

Tamil Nadu

Country

India

Facility Name

Aravind Eye Hospital

City

Madurai

State/Province

Tamil Nadu

Country

India

Facility Name

Aravind Eye Hospital

City

Pondicherry

State/Province

Tamil Nadu

Country

India

12. IPD Sharing Statement

Plan to Share IPD

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Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

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