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

Glaucoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04673604
• Other study ID #: 399
• Status: Completed
• Phase: N/A
• Start date: May 6, 2018
• Est. completion date: June 29, 2020

Study information

• Verified date: July 2022
• Source: Aristotle University Of Thessaloniki
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: June 29, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glaucoma
• Ocular Surface Disease

Intervention

Diagnostic Test:
• 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).

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

Locations

Country	Name	City	State
Greece	University Department of Ophthalmology	Thessaloniki

Sponsors (1)

Lead Sponsor	Collaborator
Aristotle University Of Thessaloniki

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Mean diurnal IOP	Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.	6 months
Secondary	Osmolarity	Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.	6-months
Secondary	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.	6 months