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

NCT ID: NCT04673604

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-06
• Study Completion Date: 2020-06-29

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.

Conditions

Glaucoma; Ocular Surface Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Triple preservative-free therapy with placebo 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 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)

Group Type: PLACEBO_COMPARATOR

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

Intervention Type: DIAGNOSTIC_TEST

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

mean diurnal intraocular pressure-lowering

Intervention Type: DRUG

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

Triple preservative-free therapy with 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)

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DIAGNOSTIC_TEST

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

mean diurnal intraocular pressure-lowering

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: DIAGNOSTIC_TEST

mean diurnal intraocular pressure-lowering

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aristotle University Of Thessaloniki

OTHER

Sponsor Role: lead

Responsible Party

AGP Konstas

Professor in Ophthalmology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andreas Katsanos, MD, PhD

Role: STUDY_DIRECTOR

University of Ioannina

Locations

University Department of Ophthalmology

Thessaloniki, , Greece

Countries

Greece

Other Identifiers

399

Identifier Type: -

Identifier Source: org_study_id