Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Macular Edema Clinical Trial

— MEND  

Official title:

Macular Edema Nepafenac vs. Difluprednate Uveitis Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01939691
• Other study ID #: 18-24978
• Status: Terminated
• Phase: Phase 4
• Start date: September 12, 2018
• Est. completion date: March 31, 2020

Study information

• Verified date: January 2021
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: March 31, 2020
• Est. primary completion date: March 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Edema
• Macular Edema
• Uveitis

Intervention

Drug:
• Difluprednate
Difluprednate 0.05% - corticosteroid eyedrop
• Nepafenac
Nepafenac 0.1% - NSAID eyedrop
• Prednisolone acetate
prednisolone acetate 1% - corticosteroid eyedrop

Locations

Country	Name	City	State
India	Aravind Eye Hospital	Coimbatore	Tamil Nadu
India	Aravind Eye Hospital	Madurai	Tamil Nadu
India	Aravind Eye Hospital	Pondicherry	Tamil Nadu

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Aravind Eye Hospitals, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central subfield thickness	Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness	4 weeks
Secondary	Resolution	proportion of patients with resolution of macular edema	4 weeks
Secondary	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	4 weeks
Secondary	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	4 weeks
Secondary	Intraocular pressure (IOP) increase	number of patients with intraocular pressure increase at least 10mmHg over baseline	4 weeks
Secondary	High IOP	Number of patients experiencing high intraocular pressure (> 24 mmHg)	4 weeks
Secondary	Visual acuity	best-corrected visual acuity (ETDRS protocol)	4 weeks