Clinical trial NCT04149210: FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial
Official title: FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Trachomatous Trichiasis (TT)
Eye Diseases
Eyelid Diseases
Trachomatous
Trichiasis
Keywords: fluorometholone 0.1%
trachomatous trichiasis
Eye Diseases
Eyelid Diseases
trachomatous
trichiasis
FLAME
TT Surgery
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: University of Pennsylvania
name: London School of Hygiene and Tropical Medicine
name: Berhan Public Health and Eye Care Consultancy PLC
name: The Fred Hollows Foundation, Ethiopia
name: The Fred Hollows Foundation, Australia
First posted: 2019-11-04
Enrollment: 2410
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 1:1 randomized, double-masked, placebo controlled clinical trial
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Incidence of postoperative TT by one year, as determined by trained study team members
timeFrame: 12 months
Secondary outcomes:
measure: Efficacy Measure 1 - Entropion
timeFrame: 1 year
measure: Efficacy Measure 2 - Reoperation
timeFrame: 1 year
measure: Efficacy Measure 3 - Lashes
timeFrame: 1 year
measure: Efficacy Measure 4 - Health economic analysis
timeFrame: 1 year
measure: Safety/adverse outcomes 1 - Corneal Opacity
timeFrame: 1 year
measure: Safety/adverse outcomes 2 - Overcorrection
timeFrame: 1 year
measure: Safety/adverse outcomes 3 - Eyelid Abnormalities
timeFrame: 1 year
measure: Safety/adverse outcome 4 - Lid Closure Defect
timeFrame: 1 year
measure: Safety/adverse outcomes 5 - Granuloma
timeFrame: 1 year
measure: Safety/adverse outcomes 6 - Pain level
timeFrame: 1 year
measure: Safety/adverse outcomes 7 - IOP in mmHg
timeFrame: 4 weeks
measure: Safety/adverse outcomes 8 - Cataract Surgery
timeFrame: 1 year
measure: Safety/adverse outcomes 9 - TT in non-study eye
timeFrame: 1 year
measure: Safety/adverse outcomes 10 - Adverse Events
timeFrame: 1 year
measure: Patient-reported outcomes 1 - Patient satisfaction
timeFrame: 1 year
measure: Patient-reported outcomes 2 - Cosmetic outcome
timeFrame: 1 year
measure: Patient-reported outcomes 3 - Health utility
timeFrame: 1 year
measure: Additional variables 1 - Visual Acuity
timeFrame: 1 year
Other outcomes:
Locations:
city: Addis Ababa
country: Ethiopia
facility: Oromia Health Bureau
Study officials:
affiliation: Massachusetts Eye and Ear Infirmary/Harvard Medical School
name: John H Kempen, MD MPH MHS PhD
role: STUDY_CHAIR
References: