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

Phase 3

Completed

• Conditions: Trachomatous Trichiasis (TT); Trichiasis; Eye Diseases; Eyelid Diseases; Trachomatous
• Interventions: Drug: Fluorometholone 0.1% Oph Susp; Drug: Artificial Tears

• Registration Number: NCT04149210
• Lead Sponsor: Massachusetts Eye and Ear Infirmary

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2019-10-12
• Study First Submitted QC: 2019-10-30
• Study First Posted: 2019-11-04
• Study Start: 2021-08-19
• Primary Completion: 2024-11-30
• Study Completion: 2024-11-30
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 2410

Inclusion Criteria

1. 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.
2. 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.
3. Collection of all baseline data prior to randomization
4. Signed, informed consent (and assent, when applicable)

Exclusion Criteria

1. 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
2. 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)
3. 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).
4. Any condition known to be present at baseline for which it is anticipated ocular or systemic corticosteroid therapy will be required.
5. 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.
6. 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
fluorometholone	Fluorometholone 0.1% Oph Susp	Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks
Artificial Tears	Artificial Tears	one drop two times daily for four weeks

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Efficacy Measure 1 - Entropion	1 year	Presence and extent of entropion of the upper eyelid
Efficacy Measure 2 - Reoperation	1 year	Number of study eyes undergoing reoperation for postoperative trichiasis
Efficacy Measure 3 - Lashes	1 year	Number and location of trichiatic lashes from the upper eyelid touching the globe
Efficacy Measure 4 - Health economic analysis	1 year	Marginal cost per case of postoperative trichiasis avoided (Cost-effectiveness in the use of Fluorometholone 0.1%)
Safety/adverse outcomes 1 - Corneal Opacity	1 year	Presence and grade of corneal opacity in study eyes
Safety/adverse outcomes 2 - Overcorrection	1 year	Presence of overcorrection in study eyes
Safety/adverse outcomes 3 - Eyelid Abnormalities	1 year	Presence of eyelid notching/eyelid contour abnormalities in study eyes
Safety/adverse outcome 4 - Lid Closure Defect	1 year	Presence of lid closure defect in study eyes
Safety/adverse outcomes 5 - Granuloma	1 year	Presence of granuloma in study eyes
Safety/adverse outcomes 6 - Pain level	1 year	Pain level in study eyes at one year scored from 1 (none) to 5 (extreme)
Safety/adverse outcomes 7 - IOP in mmHg	4 weeks	Intraocular pressure (IOP) elevation in study eyes
Safety/adverse outcomes 8 - Cataract Surgery	1 year	Occurrence of cataract surgery in study eyes
Safety/adverse outcomes 9 - TT in non-study eye	1 year	Cumulative incidence of TT in the fellow eye by one year
Safety/adverse outcomes 10 - Adverse Events	1 year	Adverse events attributed to study treatment
Patient-reported outcomes 1 - Patient satisfaction	1 year	Patient satisfaction level in regards to the trichiasis surgery outcome measured on a likert scale for satisfaction (from very dissatisfied to very satisfied)
Patient-reported outcomes 2 - Cosmetic outcome	1 year	Patient satisfaction level in regards to the cosmetic outcome of the trichiasis surgery measured on a likert scale for satisfaction (from very dissatisfied to very satisfied)
Patient-reported outcomes 3 - Health utility	1 year	Quality of life assessed using the tool EuroQol 5 Dimensions (EQ-5D) comprising mobility, self-care, usual activities, pain/discomfort and anxiety/depression dimensions and assessed on five levels from no problems to extreme problems
Additional variables 1 - Visual Acuity	1 year	Visual acuity with presenting correction in study eyes

Trial Locations

Locations (1)

Oromia Health Bureau; 🇪🇹 Addis Ababa, Ethiopia