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

Not Applicable

Completed

• Conditions: Glaucoma; Ocular Surface Disease
• Interventions: Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale); Drug: mean diurnal intraocular pressure-lowering

• Registration Number: NCT04673604
• Lead Sponsor: Aristotle University Of Thessaloniki

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.

Study Timeline

• Study Start: 2018-05-06
• Primary Completion: 2019-12-31
• Study Completion: 2020-06-29
• Study First Submitted: 2020-12-11
• Study First Submitted QC: 2020-12-16
• Study First Posted: 2020-12-17
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-19
• Last Update Posted: 2022-07-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Triple preservative-free therapy with placebo in the evening	Assessment of ocular surface staining (Oxford score 0-15 scale)	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)
Triple preservative-free therapy with placebo in the evening	mean diurnal intraocular pressure-lowering	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)
Triple preservative-free therapy with cyclosporine 0.1% in the evening	Assessment of ocular surface staining (Oxford score 0-15 scale)	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)
Triple preservative-free therapy with cyclosporine 0.1% in the evening	mean diurnal intraocular pressure-lowering	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)

Primary Outcome Measures

Name	Time	Method
Mean change from baseline in ocular staining (Oxford score)	6 months	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

Name	Time	Method
Mean diurnal IOP	6 months	Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.
Osmolarity	6-months	Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.
Matrix-metalloproteinase-9 (MMP-9) over-expression	6 months	Mean MMP-9 over-expression with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.

Trial Locations

Locations (1)

University Department of Ophthalmology; 🇬🇷 Thessaloniki, Greece