Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases, Trachomatous, Trichiasis
Conditions
Keywords
fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery
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.
Interventions
fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.
DRUGArtificial Tears
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.
Sponsors
Massachusetts Eye and Ear Infirmary
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
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Patients, surgeons, and study staff at field site are masked to the assigned treatment group of the subject.
Intervention model description
This is a 1:1 randomized, double-masked, placebo controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
15 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 at 1 year |
| Safety/Adverse Outcomes 6 - Pain Level | 1 year | Pain scale score ranges from 5 (least pain) to 20 (most pain) |
| Safety/Adverse Outcomes 7 - IOP in mmHg | 4 weeks | Intraocular pressure (IOP) elevation ≥ 10 mmHg from baseline in study eyes at week 4 |
| 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 by one year |
| 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 |
Countries
Ethiopia
Contacts
STUDY_CHAIRJohn H Kempen, MD MPH MHS PhD
Massachusetts Eye and Ear Infirmary/Harvard Medical School
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.3 Years STANDARD_DEVIATION 14.9 |
| Conjunctivalization of the lid margin grade CM0: None | 16 Study Eyes |
| Conjunctivalization of the lid margin grade CM1: posterior to the line of meibomian gland | 175 Study Eyes |
| Conjunctivalization of the lid margin grade CM2: less than 50% of the lid | 589 Study Eyes |
| Conjunctivalization of the lid margin grade CM3: greater than 50% of the lid | 823 Study Eyes |
| Corneal opacity C0: None | 2050 Study Eyes |
| Corneal opacity C1: Peripheral | 357 Study Eyes |
| Corneal opacity C2a: Off center faint | 75 Study Eyes |
| Corneal opacity C2b: Off center dense | 16 Study Eyes |
| Corneal opacity C2c: Central faint | 110 Study Eyes |
| Corneal opacity C2d: Central dense | 42 Study Eyes |
| Corneal opacity C3: Total/central dense | 10 Study Eyes |
| Corneal opacity C4: Phthisis | 0 Study Eyes |
| Diagnosed with cataract: Yes | 44 Study Eyes |
| Evidence/extent of epilation in the upper eyelid <1/3 of the lid margin | 30 Study Eyes |
| Evidence/extent of epilation in the upper eyelid ≥ 1/3 to ≤ 2/3 of the lid margin | 75 Study Eyes |
| Evidence/extent of epilation in the upper eyelid > 2/3 of the lid margin | 132 Study Eyes |
| Evidence/extent of epilation in the upper eyelid None | 1386 Study Eyes |
| IOP | 12.0 mmHg STANDARD_DEVIATION 3.2 |
| Laterality of TT Surgery Bilateral | 398 Participants |
| Laterality of TT Surgery No surgery due to withdrawal after randomization | 5 Participants |
| Laterality of TT Surgery Unilateral | 803 Participants |
| Mean total number of upper eyelid lashes touching the globe or the cornea | 3.9 Upper lid lashes touching globe/cornea STANDARD_DEVIATION 4.8 |
| Ocular Surface Disease Index (OSDI) ocular symptoms score | 48.6 scores on a scale STANDARD_DEVIATION 29.5 |
| Ocular Surface Disease Index (OSDI) total score | 37.8 scores on a scale STANDARD_DEVIATION 23.2 |
| Presenting Visual Acuity 20/20 | 103 Study Eyes |
| Presenting Visual Acuity 20/200 - 20/400 | 180 Study Eyes |
| Presenting Visual Acuity 20/25 - 20/40 | 586 Study Eyes |
| Presenting Visual Acuity 20/50 - 20/63 | 438 Study Eyes |
| Presenting Visual Acuity 20/80 - 20/160 | 665 Study Eyes |
| Presenting Visual Acuity Worse than 20/400 | 77 Study Eyes |
| Previous eye injury: Yes | 27 Study Eyes |
| Previous eye surgery: Yes | 14 Study Eyes |
| Race/Ethnicity, Customized African | 1204 Participants |
| Reading ability: unable | 1082 Participants |
| Self-reported pain or discomfort Extreme | 88 Participants |
| Self-reported pain or discomfort Moderate | 234 Participants |
| Self-reported pain or discomfort None | 316 Participants |
| Self-reported pain or discomfort Severe | 169 Participants |
| Self-reported pain or discomfort Slight | 837 Participants |
| Severity of upper eyelid trichiasis Not severe | 2118 Study Eyes |
| Severity of upper eyelid trichiasis Severe (total number of lashes ≥ 6, or epilation ≥ 1/3) | 541 Study Eyes |
| Sex: Female, Male Female | 1692 Participants |
| Sex: Female, Male Male | 350 Participants |
| Total number of upper eyelid lashes touching the globe or the cornea 0 (epilating) | 236 Study Eyes |
| Total number of upper eyelid lashes touching the globe or the cornea 10-19 | 130 Study Eyes |
| Total number of upper eyelid lashes touching the globe or the cornea 1-5 | 1058 Study Eyes |
| Total number of upper eyelid lashes touching the globe or the cornea 20+ | 43 Study Eyes |
| Total number of upper eyelid lashes touching the globe or the cornea 6-9 | 143 Study Eyes |
| Trichiasis of the lower eyelid No | 1509 Study Eyes |
| Trichiasis of the lower eyelid Yes | 155 Study Eyes |
| Type of TT surgery BLTR | 515 Study Eyes |
| Type of TT surgery No surgery due to withdrawal after randomization | 4 Study Eyes |
| Type of TT surgery PLTR | 1084 Study Eyes |
| Upper eyelid conjunctival scarring S0: None | 155 Study Eyes |
| Upper eyelid conjunctival scarring S1: Mild | 192 Study Eyes |
| Upper eyelid conjunctival scarring S2: Moderate | 1617 Study Eyes |
| Upper eyelid conjunctival scarring S3: Severe | 1271 Study Eyes |
| Upper Eyelid Entropion E0: None | 344 Study Eyes |
| Upper Eyelid Entropion E1: Mild | 598 Study Eyes |
| Upper Eyelid Entropion E2: Moderate | 905 Study Eyes |
| Upper Eyelid Entropion E3: Severe | 287 Study Eyes |
| Upper Eyelid Entropion E4: Total | 111 Study Eyes |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 1,206 | 8 / 1,204 |
| other Total, other adverse events | 382 / 1,206 | 287 / 1,204 |
| serious Total, serious adverse events | 83 / 1,206 | 88 / 1,204 |
Outcome results
None listed