Efficacy of Citicoline Eye Drops 2% on Visual Field Preservation in Patients With Open Angle Glaucoma

Summary: To evaluate the efficacy of citicoline eye drops 2% in reducing visual field deterioration in patients with progressing OAG treated according to best clinical practice. Secondary objectives are assessing the effect of citicoline eye drops 2% on changes in structural parameters measured by Spectral Domain Optical Coherence Tomography (SD-OCT) and evaluating the safety of citicoline eye drops 2%
clinicaltrials.gov

Short title: Efficacy of Citicoline Eye Drops 2% on Visual Field Preservation in Patients With Open Angle Glaucoma
clinicaltrials.gov

Official title: A Phase III Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel-group Trial of the Efficacy of Citicoline Eye Drops 2% on Visual Field Preservation in Patients With Open Angle Glaucoma
clinicaltrials.gov

Allocation: Randomised
Model: Parallel groups
Purpose: Prevention
Masking: Quadruple masking
Masking description: Double-blind
Masked roles: Participants, Care providers, Investigators, Outcome assessors

Sources for study design

Progression of visual field damage
Timeframe: 3 years
Difference in the rate of progression of VF damage in the study eye between the two trial arms. This will be measured with repeated, planned visual field (VF) tests, all performed with a Humphrey Field Analyser (HFA, Zeiss Meditec, Dublin, CA) with the SITA Standard 24-2 strategy, over the span of three years.

Rate of progression in structural parameters
Timeframe: 3 years
Difference in the rate of progression in structural parameters. These parameters focus on the ocular structures mostly damaged by glaucoma. The parameters of interest will be: * RNFL thickness measured with Optical Coherence Tomography (OCT). * Inner retina thickness in the macula (RNFL, Ganglion Cell Layer and Ganglion Cell + Inner Plexiform Layer complex).
Safety (IOP)
Timeframe: 3 years
Safety will be assured by regular assessments of adverse events and IOP. IOP will be carefully monitored and managed as per standard clinical practice (detailed management of IOP is reported later). Side effects from the neuroprotective drops or any IOP lowering treatment, including allergic reactions, ocular surface toxicity and signs of extraocular or intraocular inflammation, will be carefully assessed by the examiners and reported in the case report form (CRF). Any significant discomfort or adverse reactions to the drops or clear signs of inflammation will be reasons for early withdrawal
Visual Field recovery
Timeframe: 3 years
Evidence of neuro-recovery. The Visual field Mean Deviation values (2 tests) at Visit 2 will be compared between the two groups, after adjusting for the MD values at Visit 1 (baseline, 2 tests).

Sources for outcomes

Signed written informed consent.
Age ≥ 18 years.
Eyes with OAG, Pseudoexfoliation and pigmentary glaucoma will be included.
Best Corrected Visual Acuity (BCVA) ≥ 0.5 for the study eye.
Controlled IOP (≤ 18 mmHg, average of the last 3 measurements in the clinic) in the study eye.
Visual field MD not worse than -12 dB at the latest assessment in the clinic for the study eye.
Deteriorating MD at a rate between -0.5 dB/year and -1.0 dB/year, estimated from the latest VF tests collected in the clinic (at least 4) over a period during which incisional glaucoma surgery was not performed. Combinations of SITA Standard and Fast strategies (but not SITA Faster) is admissible. Patients who reach the desired minimum number of tests (4) with a mixture of SITA Standard/Fast and SITA Faster tests will need to perform additional replacement tests according to the prevalent strategy used in their series of VF (i.e. additional SITA Standard/Fast tests if ≤ 2 tests were SITA Faster; additional SITA Faster if > 2 tests were SITA Faster).
Glaucoma definition will be based on VF damage (24-2, any SITA strategy) and spatially congruent glaucomatous changes at the ONH. If both eyes are eligible, the eye with the better MD will be chosen as the study eye.
Women of childbearing potential willing to use an appropriate method of contraception.

Cataract in the study eye which, in the opinion of the clinician, may require cataract surgery within the next three years.
Only-eye patients (visual acuity < 0.1 decimals in one eye or more than two paracentral VF locations with a sensitivity of < 10 dB).
Known intolerance or allergy to any of the components in the eye drops.
Diode laser treatment or glaucoma surgery in the past 2 years or cataract surgery within the last 6 months in the study eye.
Eyes with any type of glaucoma other than primary, pseudoexfoliative or pigmentary OAG.
Patients with other ocular or systemic comorbidities that, in the opinion of the Investigator, might affect the VF or the execution of the test.
Patients already on topical or systemic citicoline treatment.
Patients taking other systemic or topical potential neuroprotectors competing with citicoline eye drops 2% (a list will be provided) unwilling to suspend these treatments and undergo a washout period of 6 months prior to the study.
Patients unable to perform reliable VF tests, based on the assessment of the last 4 available 24-2 Humphrey Field Analyzer (HFA) VF tests performed in the clinic with a false positive rate (FP) ≤ 15%.
Pregnant and nursing patients.

Sources for eligibility