Fluorometholone as Ancillary Therapy for TT Surgery

Fluorometholone 0.1% as Perioperative Adjunct Therapy for Lid-rotation Surgery in Trachomatous Entropion and Trichiasis, Dose-varying Study

The investigators aim to evaluate a new potentially cost-effective approach to improving trichiasis surgery outcomes, perioperative topical anti-inflammatory therapy. The investigators hypothesize that adjunctive topical fluorometholone therapy following trichiasis surgery will reduce the risk of recurrent trichiasis. The rationale for this hypothesis is that interruption of inflammation postoperatively would reduce postoperative scarring, leading to better outcomes. As an initial step toward evaluating this modality, the investigators believe it to be necessary to evaluate topical corticosteroid therapy in a safety-oriented study, for which the investigators also hypothesize that fluorometholone will have a perioperative safety profile acceptable for large-scale programmatic use. Topical corticosteroid therapy is associated with potential risks of cataract induction and intraocular pressure (IOP) elevation in susceptible individuals. Fluorometholone has lower intraocular penetration than alternative corticosteroids, with correspondingly less IOP-raising effect while still having favorable effects on conjunctival inflammation, and is a low-cost generic drug. Its poor delivery of corticosteroid into the eye itself provides an advantage in this setting, as the major side effects of therapy are the result of intraocular effects, and therapy only is needed to the conjunctiva. However, prior to use in a large-scale trial it is sensible to make sure adverse outcomes are not observed in a substantial number of TT patients in a smaller scale trial. Secondary goals of such a trial are to evaluate alternative topical corticosteroid dosing schedules to identify an optimal dosing schedule and to identify any preliminary signals of potential efficacy.

Study Overview

• Status: Completed
• Conditions: Trachoma; Trichiasis; Bilamellar Tarsal Rotation
• Intervention / Treatment: Drug: Fluorometholone 0.1% ophthalmic solution; Other: Artificial tears (Placebo)

Detailed Description

Protocol Title: Fluorometholone 0.1% as Perioperative Adjunct Therapy for Lid-rotation Surgery in Trachomatous Entropion and Trichiasis, Dose-varying Study

Study Design: Randomized, double-masked, dose-ranging study of three dose levels of fluorometholone 0.1% or placebo in one eye of subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery

Primary Study Objective: Evaluate the safety and tolerability of three (3) doses of fluorometholone 0.1% in subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation)

Secondary Study Objective: Conduct a preliminary assessment of the efficacy of three (3) doses of fluorometholone 0.1% in subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation)

Number of Subjects: Up to 156 eyes of up to 156 subjects

Study Population: Subjects with trachomatous trichiasis (TT) undergoing lid rotation surgery (Bilamellar Tarsal Rotation)

Test Articles:

1. Fluorometholone 0.1% one drop twice daily for four weeks
2. Placebo one drop twice daily for four weeks
3. Fluorometholone 0.1% one drop four times daily for four weeks
4. Placebo one drop four times daily for four weeks
5. Fluorometholone 0.1% one drop four times daily for eight weeks
6. Placebo one drop four times daily for eight weeks

Visit Schedule: Following trichiasis surgery on Day 0, subjects will return for study visits approximately on Days 14, 28, 56, 90, and 365

Tolerability Parameters:

• Treatment-emergent ocular symptoms/signs
• Discontinuation of drug / treatment because of side effects

Safety Parameters:

• Intraocular pressure elevation ≥30 mm Hg
• Cataract
• Adverse events
• Treatment emergent abnormal ophthalmic findings
• Treatment emergent external examination findings
• Visual acuity

Efficacy Parameters:

• Trichiasis recurrence
• Entropion recurrence
• Trachoma activity grade (to the extent activity can be graded in eyes with severe trachomatous scarring)

• Study Type: Interventional
• Enrollment (Actual): 154
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Ethiopia
  • Snnpr
    • Butajira, Snnpr, Ethiopia
      • Grarbet Tehadiso Mahber (Grarbet Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 years or more
2. Diagnosis with trachomatous trichiasis
3. Plan for lid rotation surgery (Bilamellar Tarsal Rotation) on at least one upper eyelid
4. LOCS 3 cataract grading is level 3 or less for the nuclear cataract scale, and level 2 or less for the cortical cataract and posterior subcapsular cataract scales.
5. Intraocular pressure between 8-20 mm Hg in the study eye.

Exclusion Criteria:

1. Contraindications to the use of the test articles
2. Known allergy or sensitivity to any medication used in this study, including the study medication or its components (e.g., fluorometholone)
3. Currently taking more than two ocular anti-hypertensive medications in the study eye (prior IOP-lowering surgery is acceptable; combinations of two agents such as Cosopt and Combigan are considered two medications)
4. Glaucoma sufficiently advanced that an intraocular pressure spike potentially would put the patient at substantial risk of vision loss, per study ophthalmologist's judgment.
5. Non-phakic (i.e., pseudophakic or aphakic) study eye (contralateral non-phakic eye is permitted).
6. Other than trachoma, any active ocular infections (bacterial, viral, or fungal), or any active ocular inflammation (e.g., scleritis, iritis).
7. History or diagnosis of ocular herpes or presence of a corneal lesion of suspected herpetic origin; or a diagnosis or suspected diagnosis of ophthalmic mycobacterial infection in either eye.
8. Corneal or scleral thinning in either eye.
9. A severe / serious ocular pathology or medical condition which may preclude study completion.
10. Any condition for which it is anticipated ocular or systemic corticosteroid therapy would be required.
11. Unwilling to discontinue use of contact lenses for the duration of the study (should the unusual circumstance of a trachomatous trichiasis patient who uses contact lenses be encountered)
12. Any significant illness or condition that could, in the investigator's or sub-investigator's opinion, be expected to interfere with the study parameters or study conduct; or put the subject at significant risk
13. For women of childbearing age, currently pregnant and/or breastfeeding, as obtained by self-report (because of concerns about the (programmatic) use of azithromycin in this setting).
14. Cataract in the study eye, defined as LOCS-3 cataract grading is level 3.1 or more for the nuclear cataract scale, or level 2.1 or more for the cortical cataract or posterior subcapsular cataract scales.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluorometholone 0.1% 1 gtt bid x4weeks; Fluorometholone 0.1% 1 drop two times daily for four weeks	Drug: Fluorometholone 0.1% ophthalmic solution
Placebo Comparator: Artificial Tears 1 gtt bid x4 weeks	Other: Artificial tears (Placebo); Artificial tears (Placebo)
Experimental: Fluorometholone 0.1% 1 gtt qid x 4 weeks; Fluorometholone 0.1% 1 drop four times daily for four weeks	Drug: Fluorometholone 0.1% ophthalmic solution
Placebo Comparator: Artificial Tears 1 gtt qid x4 weeks	Other: Artificial tears (Placebo); Artificial tears (Placebo)
Experimental: Fluorometholone 0.1% 1 gtt qid x 8 weeks; Fluorometholone 0.1% 1 drop four times daily for eight weeks	Drug: Fluorometholone 0.1% ophthalmic solution
Placebo Comparator: Artificial Tears 1 gtt qid x8 weeks	Other: Artificial tears (Placebo); Artificial tears (Placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety assessments	Incident cataract is defined as either: 1) a two-step worsening on the nuclear, cortical, and/or posterior subcapsular LOCS-3 scale; or 2) undergoing cataract surgery prior to that point in follow-up. Intraocular pressure elevation Other dose-limiting toxicity: 1) SAEs (see below) judged as likely related to the treatment by the investigators; 2) vision-threatening non-trachoma infections, e.g., corneal ulcer; 3) anaphylaxis or other events requiring immediate resuscitation; or 4) when the clinician-investigators determine that other AEs observed in a subject would make future applications of the treatment contraindicated on the basis of side effects.	Within one year of randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence of trichiasis in the study eye	Lashes touching the globe or cornea	Within one year of randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent ocular symptoms/signs	Within the period of randomized treatment (either 4 or 8 weeks from randomization)	Within 4-8 weeks
Discontinuation of drug / treatment because of side effects	During the period of treatment (either 4 or 8 weeks after randomization)	Within 4-8 weeks of randomization
Other adverse events		Within 1 year
Visual acuity	Changes from baseline. Changes could either be favorable or unfavorable.	Within 1 year
Entropion recurrence	Among cases with entropion at baseline, the incidence of entropion recurrence.	Within 1 year
Trachoma activity grade	WHO trachoma activity grade (to the extent activity can be graded in eyes with severe trachomatous scarring)	Within 1 year

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Lions Club International Foundation; Berhan Public Health and Eye Care Consultancy PLC; Grarbet Tehadiso Mahber
• Investigators: Principal Investigator: John H Kempen, MD MPH PhD, University of Pennsylvania; Principal Investigator: Wondu Alemayehu, MD, MPH, Berhan Public Health & Eye Care Consultancy PLC

Study record dates

Study Major Dates

• Study Start: November 1, 2013
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: September 19, 2013
• First Submitted That Met QC Criteria: September 23, 2013
• First Posted (Estimate): September 24, 2013

Study Record Updates

• Last Update Posted (Estimate): April 21, 2016
• Last Update Submitted That Met QC Criteria: April 20, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: placebo controlled; trachoma; trichiasis; trachomatous trichiasis; bilamellar tarsal rotation; fluorometholone
• Additional Relevant MeSH Terms: Infections; Eye Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Conjunctivitis; Conjunctival Diseases; Corneal Diseases; Chlamydiaceae Infections; Eyelid Diseases; Eye Infections, Bacterial; Eye Infections; Chlamydia Infections; Conjunctivitis, Bacterial; Trachoma; Trichiasis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Allergic Agents; Pharmaceutical Solutions; Ophthalmic Solutions; Lubricant Eye Drops; Fluorometholone
• Other Study ID Numbers: SF1707/UND