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From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy

Primary Purpose

Glaucoma, Ocular Surface Disease

Status

Completed

Phase

Not Applicable

Locations

Greece

Study Type

Interventional

Intervention

Assessment of ocular surface staining (Oxford score 0-15 scale)

mean diurnal intraocular pressure-lowering

About this trial

This is an interventional prevention trial for Glaucoma

Eligibility Criteria

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

Inclusion criteria

Adult patients with well controlled open-angle glaucoma
Patients chronically treated for more than 6 months with preserved, branded, or generic, triple antiglaucoma therapy comprising latanoprost and dorzolamide/timolol fixed combination
Subjects should have experienced at least 1 symptom of dry eye (soreness, scratchiness, dryness, grittiness, and burning)
Additionally, patients should demonstrate at least one of the objective signs for OSD at baseline: positive conjunctival staining with lissamine green and/or evidence of positive corneal staining with fluorescein (assessed with the 15-point Oxford scale),
Patients must show a BUT<8 seconds
On screening patients should show a Schirmer test without anesthesia (Schirmer-I test) ≥3 and ≤10 mm in 5 minutes.
When both eyes qualify the worse eye will be included in the study.

Exclusion criteria

Best corrected visual acuity <1/10
Patients with severe dry eye disease or Sjogren's disease
Presence of eyelid abnormality, corneal disorder or abnormality, ocular surface metaplasia, filamentous keratitis, or corneal neovascularization
Patients who have undergone ocular surgery (of any type, including laser surgery), or ocular trauma within 4 months prior to screening
Subjects who had punctal occlusion, or diathermy within 3 months prior to screening or abnormality of the nasolacrimal drainage apparatus.
Known allergy, or sensitivity to any of the study medications
Uncontrolled systemic disease, or history or active signs of ocular trauma, infection, inflammation, allergic disease, or herpes; corneal ulcers; recurrent erosions; or uveitis
Female patients will be excluded if they are pregnant, breastfeeding, planning a pregnancy, or are unwilling to use a reliable form of contraception.

Sites / Locations

University Department of Ophthalmology

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Triple preservative-free therapy with placebo in the evening

Triple preservative-free therapy with cyclosporine 0.1% in the evening

Arm Description

In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use placebo (artificial tears) in the evening (21:00) for 6 months. At the end of this period patients will be crossed over to the other therapy (cyclosporine 0.1% in the evening)

In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use cyclosporine 0.1% drops in the evening (21:00) for 6 months. At the end of this period all patients will be crossed over to the other therapy (placebo in the evening)

Outcomes

Primary Outcome Measures

Mean change from baseline in ocular staining (Oxford score)

The primary efficacy endpoint for this crossover study will be the mean change from baseline in the total ocular staining score as determined by the 15-point Oxford scale of staining on the study eye.

Secondary Outcome Measures

Mean diurnal IOP

Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.

Osmolarity

Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Matrix-metalloproteinase-9 (MMP-9) over-expression

Mean MMP-9 over-expression with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Full Information

NCT ID

NCT04673604

First Posted

December 11, 2020

Last Updated

July 19, 2022

Sponsor

Aristotle University Of Thessaloniki

1. Study Identification

Unique Protocol Identification Number

NCT04673604

Brief Title

From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy

Official Title

Changing From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy: Impact on the Rate and Severity of Ocular Surface Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Completed

Study Start Date

May 6, 2018 (Actual)

Primary Completion Date

December 31, 2019 (Actual)

Study Completion Date

June 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Aristotle University Of Thessaloniki

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

There is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen to a preservative-free (PF) one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center, prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate glaucoma therapy-related ocular surface disease from preserved to triple preservative-free therapy with and without cyclosporine 0.1% dosed in the evening.

Detailed Description

Halting and reversing glaucoma therapy-related ocular surface disease (GTR-OSD) will improve the success of long-term medical therapy, impacting millions of patients worldwide. Chronic medical therapy for glaucoma may be immensely benefitted by limiting disabling GTR-OSD, which would aid in the prevention of blindness. In 2015 a novel cationic formulation of cyclosporine A 0.1% was approved with once in the evening dosing in Europe. It is an effective, targeted immunomodulatory compound reducing inflammatory mediators and providing healing of the ocular epithelium. There remains however a paucity of published controlled evidence for GTR-OSD patients treated with this formulation. In addition, there is a lack of evidence on the impact of switching from a combined preserved anti-glaucoma regimen, to a preservative-free one, while employing sufficiently robust OSD metrics. The investigators have therefore carried out a single center prospective, crossover investigation to compare the 6-month effect of switching well controlled open-angle glaucoma patients with at least moderate GTR-OSD, from preserved to triple PF therapy with and without PF cyclosporine 0.1% dosed in the evening.

6. Conditions and Keywords

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

Glaucoma, Ocular Surface Disease

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

Masked, prospective, placebo-controlled, crossover trial of glaucoma patients with moderate to severe GTR-OSD on preserved latanoprost and dorzolamide/timolol fixed combination therapy for well-controlled open-angle glaucoma was conducted. Patients were randomized to receive preservative-free tafluprost and dorzolamide/timolol fixed combination with either topical placebo or cyclosporine 0.1% for 6 months and will then be crossed over to the opposite therapy. Oxford score of staining will be the primary outcome; osmolarity, matrix-metalloproteinase-9 testing (MMP-9), meibomian gland dysfunction (MGD), adverse events and diurnal intraocular pressure (IOP) comprise the secondary outcomes.

Masking

Outcomes Assessor

Masking Description

Only the dosing coordinator is aware of the treatment patients use.

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Triple preservative-free therapy with placebo in the evening

Arm Type

Placebo Comparator

Arm Description

Arm Title

Triple preservative-free therapy with cyclosporine 0.1% in the evening

Arm Type

Active Comparator

Arm Description

In this arm subjects will be randomized to topical therapy comprising preservative-free tafluprost drops dosed in the evening (20:30) and dorzolamide/timolol fixed combination drops administered twice daily (8:00 and 20:00). Patients will use cyclosporine 0.1% drops in the evening (21:00) for 6 months. At the end of this period all patients will be crossed over to the other therapy (placebo in the evening)

Intervention Type

Diagnostic Test

Intervention Name(s)

Assessment of ocular surface staining (Oxford score 0-15 scale)

Intervention Description

Corneal and conjunctiva staining will be recorded according to the Oxford grading scheme for ocular staining (0-15 score).

Intervention Type

Drug

Intervention Name(s)

mean diurnal intraocular pressure-lowering

Intervention Description

At the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies.

Primary Outcome Measure Information:

Title

Mean change from baseline in ocular staining (Oxford score)

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Mean diurnal IOP

Description

Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.

Time Frame

6 months

Title

Osmolarity

Description

Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Time Frame

6-months

Title

Matrix-metalloproteinase-9 (MMP-9) over-expression

Description

Mean MMP-9 over-expression with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion criteria Adult patients with well controlled open-angle glaucoma Patients chronically treated for more than 6 months with preserved, branded, or generic, triple antiglaucoma therapy comprising latanoprost and dorzolamide/timolol fixed combination Subjects should have experienced at least 1 symptom of dry eye (soreness, scratchiness, dryness, grittiness, and burning) Additionally, patients should demonstrate at least one of the objective signs for OSD at baseline: positive conjunctival staining with lissamine green and/or evidence of positive corneal staining with fluorescein (assessed with the 15-point Oxford scale), Patients must show a BUT<8 seconds On screening patients should show a Schirmer test without anesthesia (Schirmer-I test) ≥3 and ≤10 mm in 5 minutes. When both eyes qualify the worse eye will be included in the study. Exclusion criteria Best corrected visual acuity <1/10 Patients with severe dry eye disease or Sjogren's disease Presence of eyelid abnormality, corneal disorder or abnormality, ocular surface metaplasia, filamentous keratitis, or corneal neovascularization Patients who have undergone ocular surgery (of any type, including laser surgery), or ocular trauma within 4 months prior to screening Subjects who had punctal occlusion, or diathermy within 3 months prior to screening or abnormality of the nasolacrimal drainage apparatus. Known allergy, or sensitivity to any of the study medications Uncontrolled systemic disease, or history or active signs of ocular trauma, infection, inflammation, allergic disease, or herpes; corneal ulcers; recurrent erosions; or uveitis Female patients will be excluded if they are pregnant, breastfeeding, planning a pregnancy, or are unwilling to use a reliable form of contraception.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andreas Katsanos, MD, PhD

Organizational Affiliation

University of Ioannina

Official's Role

Study Director

Facility Information:

Facility Name

University Department of Ophthalmology

City

Thessaloniki

ZIP/Postal Code

55536

Country

Greece

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy

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