FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

Study Overview
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Brief Summary
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This study aims : To assess the efficacy of fluorometholone 0.1% one drop twice daily for four weeks in reducing the incidence of post-operative trachomatous trichiasis (TT) when given as adjunctive therapy with TT surgery in the programmatic setting To assess whether such treatment is sufficiently safe for wide-scale implementation in TT programs. To estimate the costs of adding fluorometholone 0.1% treatment to TT surgery per case of postoperative TT averted, and to characterize the value of such treatment under a range of plausible health economic circumstances

Detailed Description
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The investigators are pursuing an agenda to evaluate a new potentially cost-effective approach to improving trichiasis surgery outcomes: perioperative topical anti-inflammatory therapy. Inflammation-whether induced by the trachoma disease process or surgery itself-most likely contributes to progressive cicatrization leading to failure of lid rotation surgery in a clinically important proportion of TT cases. The investigators hypothesize that adjunctive topical fluorometholone therapy following trichiasis surgery will reduce the risk of recurrent trichiasis and will be acceptably safe. The rationale for the efficacy aspect of this hypothesis is that interruption of inflammation postoperatively would reduce postoperative scarring/contracture driven by ongoing disease-driven inflammation and/or surgically-induced inflammation thus reducing the incidence of TT recurrence (post-operative TT) and other inflammation-related outcomes.

Official Title
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FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

Conditions
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Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases, Trachomatous, Trichiasis

Intervention / Treatment
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* Drug: Fluorometholone 0.1% Oph Susp
* Drug: Artificial Tears


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 15 years or more, corresponding to the age of patients treated in the Fred Hollows Foundation/Federal Ministry of Health Program at field sites without general anesthesia. One or both eyes with upper lid trachomatous trichiasis-with one or more eyelashes touching the eye or evidence of epilation, with a plan to undergo TT surgery on at least one upper eyelid. Collection of all baseline data prior to randomization Signed, informed consent (and assent, when applicable) Exclusion Criteria: Contraindication(s) to the use of the test articles, including a known allergy or sensitivity to the study medication (fluorometholone) or its components, and contraindication(s) to use of azithromycin IOP≥22 mmHg and/or currently taking more than two ocular anti-hypertensive medications in the study eye (prior IOP-lowering surgery is acceptable; combinations of two IOP-lowering agents such as Dorzamol are considered two medications) A known severe / serious ocular pathology or medical condition which may preclude study completion or increase the risk of harm in the study (e.g., suspicion of non-trachomatous active ocular infection or suspicion of glaucoma of a degree to which where an intraocular pressure spike would be vision-threatening). Any condition known to be present at baseline for which it is anticipated ocular or systemic corticosteroid therapy will be required. Any significant illness or condition (e.g., hypertension with systolic blood pressure≥170 mmHg and/or diastolic blood pressure≥110 mmHg) that could, in the study team's opinion, be expected to interfere with the study parameters or study conduct; or put the subject at significant risk. Previous upper lid TT surgery on all eyes with upper lid TT. (If one eye has previously undergone upper lid TT surgery but another eye with upper lid TT has not, the patient may be enrolled, and only the latter eye will be counted for the primary analyses).

Ages Eligible for Study
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Minimum Age: 15 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
Interventional Model Description: This is a 1:1 randomized, double-masked, placebo controlled clinical trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: fluorometholone<br>Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks | Drug: Fluorometholone 0.1% Oph Susp<br>* fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.<br>* Other names: FML;|
| Placebo Comparator: Artificial Tears<br>one drop two times daily for four weeks | Drug: Artificial Tears<br>* Artificial tears (placebo) given one drop twice daily for four weeks, beginning with one drop just prior to trachomatous trichiasis surgery on the upper lid.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of postoperative TT by one year, as determined by trained study team members | The primary outcome measure is the postoperative recurrence of trachomatous trichiasis (TT), defined as one or more eyelashes touching the globe or evidence of epilation (lash stubs) on examination, or a history of repeat trichiasis surgery at any time during the one year follow-up period after the baseline surgery. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Measure 1 - Entropion | Entropion (presence and extent) | 1 year | 
| Efficacy Measure 2 - Reoperation | Reoperation for postoperative TT (recommended or done) | 1 year | 
| Efficacy Measure 3 - Lashes | Number and location of lashes touching the globe | 1 year | 
| Safety/adverse outcomes 1 - Corneal Opacity | Corneal opacity (change in proportion from baseline) | 1 year | 
| Safety/adverse outcomes 2 - Overcorrection | Overcorrection - The surgery rotates the eyelid away from the eyeball (the disease consists of inturning of the eyelid such that the lashes touch the eyeball). Overcorrection would be rotating it away from the globe. | 1 year | 
| Safety/adverse outcomes 3 - Eyelid Abnormalities | Eyelid notching/eyelid contour abnormalities | 1 year | 
| Safety/adverse outcome 4 - Lid Closure Defect | Lid closure defect | 1 year | 
| Safety/adverse outcomes 5 - Granuloma | Granuloma | 1 year | 
| Safety/adverse outcomes 7 - IOP in mmHg | IOP elevation | 4 weeks | 
| Safety/adverse outcomes 8 - Cataract Surgery | Occurrence of cataract surgery | 1 year | 
| Safety/adverse outcomes - Adverse Events | Adverse events attributed to study treatment | 1 year | 
| Additional variables 1 - Visual Acuity | Visual acuity with presenting correction | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery