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FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial (FLAME)

Primary Purpose

Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases

Status

Recruiting

Phase

Phase 3

Locations

Ethiopia

Study Type

Interventional

Intervention

Fluorometholone 0.1% Oph Susp

Artificial Tears

About this trial

This is an interventional treatment trial for Trachomatous Trichiasis (TT) focused on measuring fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery

Eligibility Criteria

15 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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)

Exclusion Criteria:

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).

Sites / Locations

Ministry of Science and Higher Education EthiopiaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

fluorometholone

Artificial Tears

Arm Description

Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks

one drop two times daily for four weeks

Outcomes

Primary Outcome Measures

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 touching the globe or evidence of epilation (lash stubs) on examination, or a history of repeat trichiasis surgery at any time during the one year follow-up period after the baseline surgery.

Secondary Outcome Measures

Efficacy Measure 1 - Entropion

Entropion (presence and extent)

Efficacy Measure 2 - Reoperation

Reoperation for postoperative TT (recommended or done)

Efficacy Measure 3 - Lashes

Number and location of lashes touching the globe

Safety/adverse outcomes 1 - Corneal Opacity

Corneal opacity (change in proportion from baseline)

Safety/adverse outcomes 2 - Overcorrection

Overcorrection - The surgery rotates the eyelid away from the eyeball (the disease consists of inturning of the eyelid such that the lashes touch the eyeball). Overcorrection would be rotating it away from the globe.

Safety/adverse outcomes 3 - Eyelid Abnormalities

Eyelid notching/eyelid contour abnormalities

Safety/adverse outcome 4 - Lid Closure Defect

Lid closure defect

Safety/adverse outcomes 5 - Granuloma

Granuloma

Safety/adverse outcomes 7 - IOP in mmHg

IOP elevation

Safety/adverse outcomes 8 - Cataract Surgery

Occurrence of cataract surgery

Safety/adverse outcomes - Adverse Events

Adverse events attributed to study treatment

Additional variables 1 - Visual Acuity

Visual acuity with presenting correction

Full Information

NCT ID

NCT04149210

First Posted

October 12, 2019

Last Updated

August 18, 2023

Sponsor

Massachusetts Eye and Ear Infirmary

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

1. Study Identification

Unique Protocol Identification Number

NCT04149210

Brief Title

FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

Acronym

FLAME

Official Title

FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 14, 2021 (Actual)

Primary Completion Date

November 30, 2024 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts Eye and Ear Infirmary

Collaborators

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Trachomatous Trichiasis (TT), Eye Diseases, Eyelid Diseases, Trachomatous, Trichiasis

Keywords

fluorometholone 0.1%, trachomatous trichiasis, Eye Diseases, Eyelid Diseases, trachomatous, trichiasis, FLAME, TT Surgery

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

This is a 1:1 randomized, double-masked, placebo controlled clinical trial

Masking

ParticipantCare ProviderInvestigator

Masking Description

There will be masking of patients, surgeons and study staff at field site to the assigned treatment group of the subject.

Allocation

Randomized

Enrollment

2254 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

fluorometholone

Arm Type

Experimental

Arm Description

Fluorometholone 0.1% eyedrops, one drop twice daily for four weeks

Arm Title

Artificial Tears

Arm Type

Placebo Comparator

Arm Description

one drop two times daily for four weeks

Intervention Type

Drug

Intervention Name(s)

Fluorometholone 0.1% Oph Susp

Other Intervention Name(s)

FML

Intervention Description

fluorometholone 0.1% one drop twice daily for four weeks, beginning with one drop just before trachomatous trichiasis surgery on the upper lid.

Intervention Type

Drug

Intervention Name(s)

Artificial Tears

Other Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Incidence of postoperative TT by one year, as determined by trained study team members

Description

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Efficacy Measure 1 - Entropion

Description

Entropion (presence and extent)

Time Frame

1 year

Title

Efficacy Measure 2 - Reoperation

Description

Reoperation for postoperative TT (recommended or done)

Time Frame

1 year

Title

Efficacy Measure 3 - Lashes

Description

Number and location of lashes touching the globe

Time Frame

1 year

Title

Safety/adverse outcomes 1 - Corneal Opacity

Description

Corneal opacity (change in proportion from baseline)

Time Frame

1 year

Title

Safety/adverse outcomes 2 - Overcorrection

Description

Time Frame

1 year

Title

Safety/adverse outcomes 3 - Eyelid Abnormalities

Description

Eyelid notching/eyelid contour abnormalities

Time Frame

1 year

Title

Safety/adverse outcome 4 - Lid Closure Defect

Description

Lid closure defect

Time Frame

1 year

Title

Safety/adverse outcomes 5 - Granuloma

Description

Granuloma

Time Frame

1 year

Title

Safety/adverse outcomes 7 - IOP in mmHg

Description

IOP elevation

Time Frame

4 weeks

Title

Safety/adverse outcomes 8 - Cataract Surgery

Description

Occurrence of cataract surgery

Time Frame

1 year

Title

Safety/adverse outcomes - Adverse Events

Description

Adverse events attributed to study treatment

Time Frame

1 year

Title

Additional variables 1 - Visual Acuity

Description

Visual acuity with presenting correction

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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) Exclusion Criteria: 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).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

John H Kempen, MD MPH MHS PhD

Phone

617-573-3202

Ext

7812480294

John_Kempen@MEEI.HARVARD.EDU

First Name & Middle Initial & Last Name or Official Title & Degree

Tony Succar, PhD MScMed(OphthSc)

Phone

6175734436

Ext

7812480294

tony_succar@meei.harvard.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

John H Kempen, MD MPH MHS PhD

Organizational Affiliation

Massachusetts Eye and Ear Infirmary/Harvard Medical School

Official's Role

Study Chair

Facility Information:

Facility Name

Ministry of Science and Higher Education Ethiopia

City

Addis Ababa

Country

Ethiopia

Individual Site Status

Recruiting

12. IPD Sharing Statement

Plan to Share IPD

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FLuorometholone as Adjunctive MEdical Therapy for TT Surgery (FLAME) Trial

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