Fluorometholone as Ancillary Therapy for TT Surgery

Study Overview
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Brief Summary
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The investigators aim to evaluate a new potentially cost-effective approach to improving trichiasis surgery outcomes, perioperative topical anti-inflammatory therapy. The investigators hypothesize that adjunctive topical fluorometholone therapy following trichiasis surgery will reduce the risk of recurrent trichiasis. The rationale for this hypothesis is that interruption of inflammation postoperatively would reduce postoperative scarring, leading to better outcomes. As an initial step toward evaluating this modality, the investigators believe it to be necessary to evaluate topical corticosteroid therapy in a safety-oriented study, for which the investigators also hypothesize that fluorometholone will have a perioperative safety profile acceptable for large-scale programmatic use. Topical corticosteroid therapy is associated with potential risks of cataract induction and intraocular pressure (IOP) elevation in susceptible individuals. Fluorometholone has lower intraocular penetration than alternative corticosteroids, with correspondingly less IOP-raising effect while still having favorable effects on conjunctival inflammation, and is a low-cost generic drug. Its poor delivery of corticosteroid into the eye itself provides an advantage in this setting, as the major side effects of therapy are the result of intraocular effects, and therapy only is needed to the conjunctiva. However, prior to use in a large-scale trial it is sensible to make sure adverse outcomes are not observed in a substantial number of TT patients in a smaller scale trial. Secondary goals of such a trial are to evaluate alternative topical corticosteroid dosing schedules to identify an optimal dosing schedule and to identify any preliminary signals of potential efficacy.

Detailed Description
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Protocol Title: Fluorometholone 0.1% as Perioperative Adjunct Therapy for Lid-rotation Surgery in Trachomatous Entropion and Trichiasis, Dose-varying Study Study Design: Randomized, double-masked, dose-ranging study of three dose levels of fluorometholone 0.1% or placebo in one eye of subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery Primary Study Objective: Evaluate the safety and tolerability of three (3) doses of fluorometholone 0.1% in subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation) Secondary Study Objective: Conduct a preliminary assessment of the efficacy of three (3) doses of fluorometholone 0.1% in subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation) Number of Subjects: Up to 156 eyes of up to 156 subjects Study Population: Subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation) Test Articles: Fluorometholone 0.1% one drop twice daily for four weeks Placebo one drop twice daily for four weeks Fluorometholone 0.1% one drop four times daily for four weeks Placebo one drop four times daily for four weeks Fluorometholone 0.1% one drop four times daily for eight weeks Placebo one drop four times daily for eight weeks Visit Schedule: Following trichiasis surgery on Day 0, subjects will return for study visits approximately on Days 14, 28, 56, 90, and 365 Tolerability Parameters: Treatment-emergent ocular symptoms/signs Discontinuation of drug / treatment because of side effects Safety Parameters: Intraocular pressure elevation ≥30 mm Hg Cataract Adverse events Treatment emergent abnormal ophthalmic findings Treatment emergent external examination findings Visual acuity Efficacy Parameters: Trichiasis recurrence Entropion recurrence Trachoma activity grade (to the extent activity can be graded in eyes with severe trachomatous scarring)

Official Title
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Fluorometholone 0.1% as Perioperative Adjunct Therapy for Lid-rotation Surgery in Trachomatous Entropion and Trichiasis, Dose-varying Study

Conditions
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Trichiasis, Trachoma, Bilamellar Tarsal Rotation

Intervention / Treatment
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* Drug: Fluorometholone 0.1% ophthalmic solution
* Other: Artificial tears (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or more Diagnosis with trachomatous trichiasis Plan for lid rotation surgery (Bilamellar Tarsal Rotation) on at least one upper eyelid LOCS 3 cataract grading is level 3 or less for the nuclear cataract scale, and level 2 or less for the cortical cataract and posterior subcapsular cataract scales. Intraocular pressure between 8-20 mm Hg in the study eye. Exclusion Criteria: Contraindications to the use of the test articles Known allergy or sensitivity to any medication used in this study, including the study medication or its components (e.g., fluorometholone) Currently taking more than two ocular anti-hypertensive medications in the study eye (prior IOP-lowering surgery is acceptable; combinations of two agents such as Cosopt and Combigan are considered two medications) Glaucoma sufficiently advanced that an intraocular pressure spike potentially would put the patient at substantial risk of vision loss, per study ophthalmologist's judgment. Non-phakic (i.e., pseudophakic or aphakic) study eye (contralateral non-phakic eye is permitted). Other than trachoma, any active ocular infections (bacterial, viral, or fungal), or any active ocular inflammation (e.g., scleritis, iritis). History or diagnosis of ocular herpes or presence of a corneal lesion of suspected herpetic origin; or a diagnosis or suspected diagnosis of ophthalmic mycobacterial infection in either eye. Corneal or scleral thinning in either eye. A severe / serious ocular pathology or medical condition which may preclude study completion. Any condition for which it is anticipated ocular or systemic corticosteroid therapy would be required. Unwilling to discontinue use of contact lenses for the duration of the study (should the unusual circumstance of a trachomatous trichiasis patient who uses contact lenses be encountered) Any significant illness or condition that could, in the investigator's or sub-investigator's opinion, be expected to interfere with the study parameters or study conduct; or put the subject at significant risk For women of childbearing age, currently pregnant and/or breastfeeding, as obtained by self-report (because of concerns about the (programmatic) use of azithromycin in this setting). Cataract in the study eye, defined as LOCS-3 cataract grading is level 3.1 or more for the nuclear cataract scale, or level 2.1 or more for the cortical cataract or posterior subcapsular cataract scales.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluorometholone 0.1% 1 gtt bid x4weeks<br>Fluorometholone 0.1% 1 drop two times daily for four weeks | Drug: Fluorometholone 0.1% ophthalmic solution<br> <br> |
| Placebo Comparator: Artificial Tears 1 gtt bid x4 weeks<br> | Other: Artificial tears (Placebo)<br>* Artificial tears (Placebo)<br>|
| Experimental: Fluorometholone 0.1% 1 gtt qid x 4 weeks<br>Fluorometholone 0.1% 1 drop four times daily for four weeks | Drug: Fluorometholone 0.1% ophthalmic solution<br> <br> |
| Placebo Comparator: Artificial Tears 1 gtt qid x4 weeks<br> | Other: Artificial tears (Placebo)<br>* Artificial tears (Placebo)<br>|
| Experimental: Fluorometholone 0.1% 1 gtt qid x 8 weeks<br>Fluorometholone 0.1% 1 drop four times daily for eight weeks | Drug: Fluorometholone 0.1% ophthalmic solution<br> <br> |
| Placebo Comparator: Artificial Tears 1 gtt qid x8 weeks<br> | Other: Artificial tears (Placebo)<br>* Artificial tears (Placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments | Incident cataract is defined as either: 1) a two-step worsening on the nuclear, cortical, and/or posterior subcapsular LOCS-3 scale; or 2) undergoing cataract surgery prior to that point in follow-up. Intraocular pressure elevation Other dose-limiting toxicity: 1) SAEs (see below) judged as likely related to the treatment by the investigators; 2) vision-threatening non-trachoma infections, e.g., corneal ulcer; 3) anaphylaxis or other events requiring immediate resuscitation; or 4) when the clinician-investigators determine that other AEs observed in a subject would make future applications of the treatment contraindicated on the basis of side effects. | Within one year of randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of trichiasis in the study eye | Lashes touching the globe or cornea | Within one year of randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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trachoma, trichiasis, trachomatous trichiasis, bilamellar tarsal rotation, fluorometholone, placebo controlled