UveitisPhase 4MENDNCT01939691
Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
A Phase 4 study testing Difluprednate, Nepafenac and Prednisolone acetate in people with Uveitis and Macular Edema, run by University of California, San Francisco at 3 sites in India.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveitis, Macular Edema
- What is being tested?
- Difluprednate, Nepafenac and Prednisolone acetate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesIndia
- Study dates
- 12 Sep 2018to 31 Mar 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
3 sites in 1 country.
India3 sites
Aravind Eye Hospital
Coimbatore, Tamil Nadu
Aravind Eye Hospital
Madurai, Tamil Nadu
Aravind Eye Hospital
Pondicherry, Tamil Nadu
About this study
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.
Read the 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.
- Conditions
- Uveitis, Macular Edema
- Being tested
- Difluprednate, Nepafenac, Prednisolone acetate
- Keywords
- difluprednate, prednisolone acetate, nepafenac
- Medical subject headings
- Uveitis, Macular Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DifluprednateDrug
Also called Durezol
Difluprednate 0.05% - corticosteroid eyedrop
NepafenacDrug
Also called Nevanac
Nepafenac 0.1% - NSAID eyedrop
Prednisolone acetateDrug
Also called Pred Forte, Econo Pred
prednisolone acetate 1% - corticosteroid eyedrop
| Study group | Role | What they receive |
|---|---|---|
| Difluprednate | Experimental | 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. Receives: Drug: Difluprednate |
| Nepafenac plus Prednisolone acetate | Experimental | 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. Receives: Drug: Nepafenac; Drug: Prednisolone acetate |
| Difluprednate plus Nepafenac | Experimental | 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. Receives: Drug: Difluprednate; Drug: Nepafenac |
What is being measured
The primary outcome is the main question the study is designed to answer.
Central subfield thickness
Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness
Measured: 4 weeks
Secondary outcomes (6)
Resolution
proportion of patients with resolution of macular edema
Measured: 4 weeks
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
Measured: 4 weeks
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
Measured: 4 weeks
Intraocular pressure (IOP) increase
number of patients with intraocular pressure increase at least 10mmHg over baseline
Measured: 4 weeks
High IOP
Number of patients experiencing high intraocular pressure (> 24 mmHg)
Measured: 4 weeks
Visual acuity
best-corrected visual acuity (ETDRS protocol)
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2013 (estimated)
- Study start12 Sep 2018
- Primary completion31 Mar 2020
- Study completion31 Mar 2020
Why it stopped: Difficulty enrolling
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for UveitisStudies of the same condition, open and under way.
- More trials run by University of California, San FranciscoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Responsible party
- Sponsor
- Investigators
- Nisha Acharya, MD MS, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01939691
- Sponsor's protocol ID
- 18-24978
- Acronym
- MEND
- Status last verified
- Jan 2021
- First submitted
- 6 Sep 2013
- Last updated
- 13 Jan 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Macular Edema Nepafenac vs. Difluprednate Uveitis Trial
- ClinicalTrials.gov ID
- NCT01939691
- Acronym / sponsor ID
- MEND / 18-24978
- Conditions
- Uveitis, Macular Edema
- Keywords
- difluprednate, prednisolone acetate, nepafenac
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty enrolling
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Collaborators
- Aravind Eye Hospitals, India
- Study start
- 12 Sep 2018 (actual)
- Primary completion
- 31 Mar 2020 (actual)
- Study completion
- 31 Mar 2020 (actual)
- First posted
- 11 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized 3 arm (1:1:1) parallel design comparative effectiveness trial
| Arm | Type | Receives |
|---|---|---|
| Difluprednate | Experimental | Drug: DifluprednateDifluprednate 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 plus Prednisolone acetate | Experimental | Drug: Nepafenac, Drug: Prednisolone acetateNepafenac 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. |
| Difluprednate plus Nepafenac | Experimental | Drug: Difluprednate, Drug: NepafenacNepafenac 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DifluprednateAlso: DurezolDifluprednate 0.05% - corticosteroid eyedrop | Drug | Difluprednate, Difluprednate plus Nepafenac |
| NepafenacAlso: NevanacNepafenac 0.1% - NSAID eyedrop | Drug | Difluprednate plus Nepafenac, Nepafenac plus Prednisolone acetate |
| Prednisolone acetateAlso: Pred Forte, Econo Predprednisolone acetate 1% - corticosteroid eyedrop | Drug | Nepafenac plus Prednisolone acetate |
Primary outcome
Central subfield thickness
Time frame: 4 weeks
Central subfield thickness measured by spectral domain optical coherence tomography adjusting for baseline thickness
6 secondary outcomes
Resolution
Time frame: 4 weeks
Improvement
Time frame: 4 weeks
recurrence
Time frame: 4 weeks
Intraocular pressure (IOP) increase
Time frame: 4 weeks
High IOP
Time frame: 4 weeks
Visual acuity
Time frame: 4 weeks
Results and safety
The study was stopped early (reason given: Difficulty enrolling). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2021.
- Individual participant dataSharing planned: No
Related trials for Uveitis
RecruitingPhase 3
A Study of Apremilast in Children With Oral Ulcers Associated With Behçet's Disease or Juvenile Psoriatic Arthritis
Behçet's Disease, Juvenile Psoriatic Arthritis
Not yet recruiting
Efficacy and Safety of Adalimumab for the Treatment of Ocular Inflammation
Non-infectious Anterior Uveitis, Non-infectious Intermediate Uveitis
RecruitingObservational study
A Study of Uveitis in Children <18 Years of Age
Uveitis
Active, not recruitingPhase 2
Multicenter Study on the Efficacy and Safety of OCS-01 in Subjects With Uveitis Related and Post Surgical Macular Edema
Uveitis Related Cystoid Macular Edema, Cystoid Macular Edema, Postoperative
RecruitingPhase 1
A Proof-of-concept Trial to EvaluAte the efficaCy and Safety Of Cell Therapy TRX103 in Patients With Active, Non-infectious Uveitis
Non Infectious Uveitis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nisha Acharya, MD MS principal investigator
University of California, San Francisco
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Difluprednate, Nepafenac and Prednisolone acetate in people with Uveitis and Macular Edema, run by University of California, San Francisco at 3 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Difficulty enrolling). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Central subfield thickness (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2021.