GlaucomaNCT04673604
From Preserved, to Preservative-free Cyclosporine 0.1% Enhanced Triple Glaucoma Therapy
A study testing Assessment of ocular surface staining (Oxford score 0-15 scale) and mean diurnal intraocular pressure-lowering in people with Glaucoma and Ocular Surface Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Glaucoma, Ocular Surface Disease
- What is being tested?
- Assessment of ocular surface staining (Oxford score 0-15 scale) and mean diurnal intraocular pressure-lowering
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteGreece
- Study dates
- 6 May 2018to 29 Jun 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Assessment of ocular surface staining (Oxford score 0-15 scale), mean diurnal intraocular pressure-lowering
- Medical subject headings
- Glaucoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
mean diurnal intraocular pressure-loweringDrug
At the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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) Receives: Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale); Drug: mean diurnal intraocular pressure-lowering |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (3)
Mean diurnal IOP
Mean diurnal intraocular pressure with the two preservative-free therapies versus preserved baseline will be evaluated as secondary endpoint.
Measured: 6 months
Osmolarity
Mean tear osmolarity with the two PF therapies versus preserved baseline will be evaluated as secondary endpoint.
Measured: 6-months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start6 May 2018
- Primary completion31 Dec 2019
- Study completion29 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlaucomaStudies of the same condition, open and under way.
- More trials run by Aristotle University Of ThessalonikiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aristotle University Of Thessaloniki
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, AGP Konstas, Aristotle University Of Thessaloniki
- Investigators
- Andreas Katsanos, MD, PhD, Study director, University of Ioannina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04673604
- Sponsor's protocol ID
- 399
- Status last verified
- Jul 2022
- First submitted
- 11 Dec 2020
- Last updated
- 20 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04673604
- Acronym / sponsor ID
- 399
- Conditions
- Glaucoma, Ocular Surface Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Aristotle University Of ThessalonikiUniversity, hospital or other
- Study start
- 6 May 2018 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 29 Jun 2020 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Triple preservative-free therapy with placebo in the evening | Placebo comparator | Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale), Drug: mean diurnal intraocular pressure-loweringIn 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 | Active comparator | Diagnostic Test: Assessment of ocular surface staining (Oxford score 0-15 scale), Drug: mean diurnal intraocular pressure-loweringIn 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) |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Diagnostic test | Triple preservative-free therapy with cyclosporine 0.1% in the evening, Triple preservative-free therapy with placebo in the evening |
| mean diurnal intraocular pressure-loweringAt the end of each 6-month period patients will undergo diurnal intraocular pressure assessment with both therapies. | Drug | Triple preservative-free therapy with cyclosporine 0.1% in the evening, Triple preservative-free therapy with placebo in the evening |
Primary outcome
Mean change from baseline in ocular staining (Oxford score)
Time frame: 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.
3 secondary outcomes
Mean diurnal IOP
Time frame: 6 months
Osmolarity
Time frame: 6-months
Matrix-metalloproteinase-9 (MMP-9) over-expression
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Katsanos, MD, PhD study director
University of Ioannina
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Assessment of ocular surface staining (Oxford score 0-15 scale) and mean diurnal intraocular pressure-lowering in people with Glaucoma and Ocular Surface Disease, run by Aristotle University Of Thessaloniki at 1 site in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean change from baseline in ocular staining (Oxford score) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2022; AzTrials last refreshed its copy on 8 Nov 2026.