Clinical trial NCT01939691: Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
Official title: Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Uveitis
Macular Edema
Keywords: difluprednate
prednisolone acetate
nepafenac
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Aravind Eye Hospitals, India
First posted: 2013-09-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Central subfield thickness
timeFrame: 4 weeks
Secondary outcomes:
measure: Resolution
timeFrame: 4 weeks
measure: Improvement
timeFrame: 4 weeks
measure: recurrence
timeFrame: 4 weeks
measure: Intraocular pressure (IOP) increase
timeFrame: 4 weeks
measure: High IOP
timeFrame: 4 weeks
measure: Visual acuity
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Coimbatore
country: India
facility: Aravind Eye Hospital
state: Tamil Nadu
city: Madurai
country: India
facility: Aravind Eye Hospital
state: Tamil Nadu
city: Pondicherry
country: India
facility: Aravind Eye Hospital
state: Tamil Nadu
Study officials:
affiliation: University of California, San Francisco
name: Nisha Acharya, MD MS
role: PRINCIPAL_INVESTIGATOR
References: