Clinical trial NCT01175902: Intraocular Pressure and Ocular Perfusion Pressure of Cosopt in Normal Tension Glaucoma
Official title: To Prove the Non-inferiority of Cosopt Compared to Xalatan in the Aspects of Intraocular Pressure and Ocular Perfusion Pressure in Subjects With Normal Tension Glaucoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Normal Tension Glaucoma
Keywords: Normal tension glaucoma
Lead sponsor: The Catholic University of Korea
Sponsor class: OTHER
Collaborators: name: Seoul St. Mary's Hospital
First posted: 2010-08-05
Enrollment: 44
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To prove the non-inferiority of the fixed timolol-dorzolamide combination (Cosopt) compared to 0.005% latanoprost (Xalatan) in the aspects of intraocular pressure (IOP) and ocular perfusion pressure (OPP) in subjects with normal tension glaucoma (NTG)

Clinical hypotheses. Primary hypothesis

* Cosopt group is non-inferior to Xalatan group in diurnal IOP reduction.

Secondary hypothesis

* Cosopt group is non-inferior to Xalatan group in diurnal diastolic and systolic OPP.

Detailed description: Cosopt (dorzolamide/timolol fixed combination) has well known effect for IOP reduction in POAG and OHT.3-5 However, there is no study about the effect and safety of Cosopt in NTG, Cosopt is not used the first line drug in the management of NTG.

In Korea, the prevalence of NTG is higher than western countries, the majority (about 80-90%) of open angle glaucoma patients have an IOP of 21 mmHg or less, so the study of NTG is important and searching of effective drug for the treatment of NTG is necessary.

In this study, we would prove the non-inferiority of Cosopt compared to Xalatan,6 which is used as a first line drug in the management of NTG, in the aspects of IOP and OPP including diastolic OPP (DOPP).

A prospective, interventional, randomized, crossover, single masked, single center study. Forty-four NTG patients were randomly allocated to one of two groups. Patients in group A were treated with Cosopt, lubricant, and Xalatan for 4 weeks each, whereas patients in group B were treated with Xalatan, lubricant, and Cosopt for 4 weeks each.

Recruit NTG patients, who are not treated with the glaucoma medication recent 2 months. If treated, after washout period of 4 weeks, the patients can be included in the study. Baseline IOP, systolic and diastolic BP will be measured. (Day 1) After 4 weeks of treatment of Cosopt or Xalatan, all participants will be checked diurnal IOP, systolic and diastolic BP. IOP was measured by Goldmann applanation tonometry (mean of three consecutive readings) with the patient in a sitting position at the slit lamp. Every IOP will be measured by one masked glaucoma specialist who is unaware of the treatment assignments. After the IOP measurements, after a 5-minite rest, pulse rate and BP (systolic and diastolic) of radial artery were measured in the sitting position using a standard automated blood pressure cuff. During the period, all measuring instruments keep to be calibrated by the manufacturer's instruction.

- OPP was calculated according to the following formula: OPP=(1/3 systolic BP + 2/3 diastolic BP) x 2/3 -IOP, diastolic OPP (DOPP)=diastolic BP-IOP. During the 4 weeks washout period, subjects will use lubricants.(Week 8) In this crossover study, with the other eye drops, the same measurement will be performed. (Week 12)

Eligibility criteria: The identification of NTG was based on reproducible glaucomatous visual field defects, corresponding to typical ONH changes.

Unilateral or bilateral visual field loss (description as below) as determined by at least two consecutive automated static threshold perimetry tests.

One eye is randomly selected in the cases where both eyes are treated.

Inclusion criteria:

1. age ranging from 45 to 75 years
2. best-corrected visual acuity no worse than 20/30 Snellen equivalent
3. optic nerve head cupping (i.e., a vertical cup-to-disc ratio of more than 0.6) and/or notching of neuroretinal rim, and/or retinal nerve fiber defects characteristic of glaucoma
4. visual field loss (i.e., a localized defect with at least three adjacent nonedge points depressed \>5 dB from the normal value, and a nucleus of at least one point depressed 10 dB from the normal value)
5. repeated measurements of untreated IOP, which documented values less than 22 mmHg
6. central corneal thickness ranging from 540 to 560 microns
7. open-angle confirmed by gonioscopy

Exclusion criteria:

1. active or chronic systemic diseases and/or concomitant assumption of any medication known to affect IOP, BP and/or HR
2. corneal abnormalities preventing reliable applanation tonometry
3. severe ocular trauma, ocular inflammation or infection, intraocular surgery or argon laser treatment or laser trabeculoplasty
4. myopic or other fundus changes preventing reliable optic disc evaluation,
5. visual field defects caused by nonglaucomatous disease
6. history of allergy to the ingredients of Cosopt or Xalatan eye drops

Primary outcomes:
measure: Intraocular Pressure (IOP), Period 1
timeFrame: 4 weeks
measure: Intraocular Pressure (IOP), Period 2
timeFrame: 12 weeks
measure: Blood Pressure (BP), Period 1
timeFrame: 4 weeks
measure: Blood Pressure (BP), Period 2
timeFrame: 12 weeks
Secondary outcomes:
measure: Ocular Perfusion Pressure (OPP), Period 1
timeFrame: 4 weeks
measure: OPP, Period 2
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's hospital
Study officials:
affiliation: The Catholic University of Korea
name: Chan Kee Park, M.D., PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee NY, Park HY, Park CK. Comparison of the Effects of Dorzolamide/Timolol Fixed Combination versus Latanoprost on Intraocular Pressure and Ocular Perfusion Pressure in Patients with Normal-Tension Glaucoma: A Randomized, Crossover Clinical Trial. PLoS One. 2016 Jan 12;11(1):e0146680. doi: 10.1371/journal.pone.0146680. eCollection 2016.