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

NCT04673604 | Completed DMC

• 1 other identifier: 399
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

Glaucoma; Ocular Surface Disease

Outcome Measures

Primary Outcomes (1)

• 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.

  6 months

Secondary Outcomes (3)

• Mean diurnal IOP

  6 months

• Osmolarity

  6-months

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

  6 months

Study Arms (2)

Triple preservative-free therapy with placebo in the evening

PLACEBO COMPARATOR

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)

Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale); Drug: mean diurnal intraocular pressure-lowering

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

ACTIVE COMPARATOR

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)

Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale); Drug: mean diurnal intraocular pressure-lowering

Interventions

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

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

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

mean diurnal intraocular pressure-lowering 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; Triple preservative-free therapy with placebo in the evening

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

University Department of Ophthalmology

Thessaloniki, 55536, Greece

Location

MeSH Terms

Conditions

Glaucoma

Condition Hierarchy (Ancestors)

Ocular Hypertension; Eye Diseases

Study Officials

• Andreas Katsanos, MD, PhD

  University of Ioannina

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Only the dosing coordinator is aware of the treatment patients use.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Ophthalmology

Model Details: 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.

Study Record Dates

• First Submitted: December 11, 2020
• First Posted: December 17, 2020
• Study Start: May 6, 2018
• Primary Completion: December 31, 2019
• Study Completion: June 29, 2020
• Last Updated: July 20, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)