Fluorometholone as Ancillary Therapy for TT Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by University of Pennsylvania
Sponsor:
Collaborators:
Lions Clubs International Foundation (funding)
Berhan Public Health and Eye Care Consultancy PLC
Grarbet Tehadiso Mahber
Information provided by (Responsible Party):
John Kempen, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01949454
First received: September 19, 2013
Last updated: November 8, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention
Trichiasis
Trachoma
Bilamellar Tarsal Rotation
Drug: Fluorometholone 0.1% ophthalmic solution
Other: Artificial tears (Placebo)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fluorometholone 0.1% as Perioperative Adjunct Therapy for Lid-rotation Surgery in Trachomatous Entropion and Trichiasis, Dose-varying Study

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Safety assessments [ Time Frame: Within one year of randomization ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Recurrence of trichiasis in the study eye [ Time Frame: Within one year of randomization ] [ Designated as safety issue: No ]
    Lashes touching the globe or cornea


Other Outcome Measures:
  • Treatment-emergent ocular symptoms/signs [ Time Frame: Within 4-8 weeks ] [ Designated as safety issue: Yes ]
    Within the period of randomized treatment (either 4 or 8 weeks from randomization)

  • Discontinuation of drug / treatment because of side effects [ Time Frame: Within 4-8 weeks of randomization ] [ Designated as safety issue: Yes ]
    During the period of treatment (either 4 or 8 weeks after randomization)

  • Other adverse events [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]
  • Visual acuity [ Time Frame: Within 1 year ] [ Designated as safety issue: Yes ]
    Changes from baseline. Changes could either be favorable or unfavorable.

  • Entropion recurrence [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    Among cases with entropion at baseline, the incidence of entropion recurrence.

  • Trachoma activity grade [ Time Frame: Within 1 year ] [ Designated as safety issue: No ]
    WHO trachoma activity grade (to the extent activity can be graded in eyes with severe trachomatous scarring)


Estimated Enrollment: 156
Study Start Date: November 2013
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01949454

Contacts
Contact: John H Kempen, MD, MPH, PhD +1 215 615 1500 john.kempen@Uphs.upenn.edu
Contact: Wondu Alemayehu, MD, MPH +251 1115539409 walemayehu@berhan-health.org

Locations
Ethiopia
Grarbet Tehadiso Mahber (Grarbet Hospital) Recruiting
Butajira, Snnpr, Ethiopia
Contact: Redda Tekla Haimanot, MD         
Contact: Menilik , MPH       menilikalem@gmail.com   
Principal Investigator: Redda Tekle Haimanot, MD         
Sponsors and Collaborators
University of Pennsylvania
Lions Clubs International Foundation (funding)
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
  More Information

No publications provided

Responsible Party: John Kempen, Professor, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01949454     History of Changes
Other Study ID Numbers: SF1707/UND
Study First Received: September 19, 2013
Last Updated: November 8, 2013
Health Authority: Ethiopia: National Research Ethics Review Committee (NRERC), Ministry of Science and Technology
Ethiopia: Food, Medicine and Health Care Administration and Control Authority of Ethiopia

Keywords provided by University of Pennsylvania:
trachoma
trichiasis
trachomatous trichiasis
bilamellar tarsal rotation
fluorometholone
placebo controlled

Additional relevant MeSH terms:
Eye Infections, Bacterial
Eye Infections
Trachoma
Trichiasis
Conjunctivitis, Bacterial
Bacterial Infections
Chlamydia Infections
Chlamydiaceae Infections
Gram-Negative Bacterial Infections
Infection
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Corneal Diseases
Eyelid Diseases
Ophthalmic Solutions
Fluorometholone
Pharmaceutical Solutions
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Anti-Allergic Agents

ClinicalTrials.gov processed this record on August 28, 2014