Trachomatous Trichiasis (TT)Phase 3FLAMENCT04149210
FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial
A Phase 3 study testing Fluorometholone 0.1% Oph Susp and Artificial Tears in people with Trachomatous Trichiasis (TT) and Eye Diseases, run by Massachusetts Eye and Ear Infirmary at 1 site in Ethiopia.
Trial 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… Read more about this study
- Who is it for?
- Ages 15 years and older
- Conditions the study is for
- Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases
- What is being tested?
- Fluorometholone 0.1% Oph Susp and Artificial Tears
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,410 participants
- Where
- 1 siteEthiopia
- Study dates
- 19 Aug 2021to 30 Nov 2024
- Phase
- Phase 3
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 15 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
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
Read the 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.
- Being tested
- Fluorometholone 0.1% Oph Susp, Artificial Tears
- Keywords
- fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery
- Medical subject headings
- Eye Diseases, Eyelid Diseases, Trichiasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fluorometholone 0.1% Oph SuspDrug
Also called FML
fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.
Artificial TearsDrug
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| fluorometholone | Experimental | Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks Receives: Drug: Fluorometholone 0.1% Oph Susp |
| Artificial Tears | Placebo comparator | one drop two times daily for four weeks Receives: Drug: Artificial Tears |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 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.
Measured: 12 months
Secondary outcomes (18)
Efficacy Measure 1 - Entropion
Presence and extent of entropion of the upper eyelid
Measured: 1 year
Efficacy Measure 2 - Reoperation
Number of study eyes undergoing reoperation for postoperative trichiasis
Measured: 1 year
Efficacy Measure 3 - Lashes
Number and location of trichiatic lashes from the upper eyelid touching the globe
Measured: 1 year
Efficacy Measure 4 - Health Economic Analysis
Marginal cost per case of postoperative trichiasis avoided (Cost-effectiveness in the use of Fluorometholone 0.1%)
Measured: 1 year
Safety/Adverse Outcomes 1 - Corneal Opacity
Presence and grade of corneal opacity in study eyes
Measured: 1 year
Safety/Adverse Outcomes 2 - Overcorrection
Presence of overcorrection in study eyes
Measured: 1 year
Safety/Adverse Outcomes 3 - Eyelid Abnormalities
Presence of eyelid notching/eyelid contour abnormalities in study eyes
Measured: 1 year
Safety/Adverse Outcome 4 - Lid Closure Defect
Presence of lid closure defect in study eyes
Measured: 1 year
Safety/Adverse Outcomes 5 - Granuloma
Presence of granuloma in study eyes at 1 year
Measured: 1 year
Safety/Adverse Outcomes 6 - Pain Level
Pain scale score ranges from 5 (least pain) to 20 (most pain)
Measured: 1 year
Safety/Adverse Outcomes 7 - IOP in mmHg
Intraocular pressure (IOP) elevation ≥ 10 mmHg from baseline in study eyes at week 4
Measured: 4 weeks
Safety/Adverse Outcomes 8 - Cataract Surgery
Occurrence of cataract surgery in study eyes
Measured: 1 year
Safety/Adverse Outcomes 9 - TT in Non-study Eye
Cumulative incidence of TT in the fellow eye by one year
Measured: 1 year
Safety/Adverse Outcomes 10 - Adverse Events
Adverse events attributed to study treatment by one year
Measured: 1 year
Patient-reported Outcomes 1 - Patient Satisfaction
Patient satisfaction level in regards to the trichiasis surgery outcome measured on a likert scale for satisfaction (from very dissatisfied to very satisfied)
Measured: 1 year
Patient-reported Outcomes 2 - Cosmetic Outcome
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)
Measured: 1 year
Patient-reported Outcomes 3 - Health Utility
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
Measured: 1 year
Additional Variables 1 - Visual Acuity
Visual acuity with presenting correction in study eyes
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 2019
- Study start19 Aug 2021
- Primary completion30 Nov 2024
- Study completion30 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Trachomatous Trichiasis (TT)Studies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a 1:1 randomized, double-masked, placebo controlled clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2,410 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts Eye and Ear Infirmary
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, London School of Hygiene and Tropical Medicine, Berhan Public Health and Eye Care Consultancy PLC, The Fred Hollows Foundation, Ethiopia, The Fred Hollows Foundation, Australia
- Responsible party
- Principal investigator, John Harold Kempen, Massachusetts Eye and Ear Infirmary
- Investigators
- John H Kempen, MD MPH MHS PhD, Study chair, Massachusetts Eye and Ear Infirmary/Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04149210
- Sponsor's protocol ID
- 2019P002286
- Acronym
- FLAME
- Status last verified
- Mar 2026
- First submitted
- 12 Oct 2019
- Last updated
- 24 Mar 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kempen JH, Abashawl A, Mohammed AA, Dodson S, Alemayehu W, Jin F, Gemechu A, Mengesha AA, Kumsa DA, Chen Y, McWilliams K, Tulu B, Abdela G, Megersa A, Cheru T, Mohammad G, Succar T, Bunya VY, Frick KD, Maguire MG, Burton MJ, Ying GS; FLAME Trial Research Group. Evaluation of fluorometholone as adjunctive medical therapy for trachomatous trichiasis surgery (FLAME): a parallel, double-blind, randomised controlled field trial in the Jimma Zone, Ethiopia. Lancet Glob Health. 2026 Mar;14(3):e395-e406. doi: 10.1016/S2214-109X(25)00493-0. Epub 2026 Jan 12.
PubMed 41539314Kempen JH, Chen Y, Abashawl A, Mohammed AA, Dodson S, Alemayehu W, Gemechu A, Mengesha AA, Kumsa DA, Succar T, McWilliams K, Jin F, Bunya VY, Maguire MG, Burton MJ, Ying GS; FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial Research Group. Outcomes of posterior lamellar tarsal rotation vs bilamellar tarsal rotation for trachomatous trichiasis. PLoS Negl Trop Dis. 2025 Jul 30;19(7):e0013152. doi: 10.1371/journal.pntd.0013152. eCollection 2025 Jul.
PubMed 40737343Mohammed AA, Abashawl A, Dodson S, Alemayehu W, Gemechu A, Abateneh A, Kumsa D, Succar T, Chen Y, McWilliams K, Bunya VY, Maguire MG, Burton MJ, Ying GS, Kempen JH; FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial Research Group. The FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial: Study Design. Ophthalmic Epidemiol. 2024 Dec;31(6):611-619. doi: 10.1080/09286586.2024.2415052. Epub 2024 Dec 10.
PubMed 39656933Mohammed AA, Abashawl A, Dodson S, Alemayehu W, Gemechu A, Mengesha AA, Kumsa D, Succar T, Chen Y, McWilliams K, Bunya VY, Maguire MG, Burton MJ, Ying GS, Kempen JH; FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial Research Group. The FLuorometholone as Adjunctive MEdical Therapy for Trachomatous Trichiasis Surgery (FLAME) Trial: Study Design. medRxiv [Preprint]. 2024 Jul 7:2024.06.26.24308549. doi: 10.1101/2024.06.26.24308549.
PubMed 39006430