Intraocular Pressure and Ocular Perfusion Pressure of Cosopt in Normal Tension Glaucoma

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

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.

Study Overview

• Status: Completed
• Conditions: Normal Tension Glaucoma
• Intervention / Treatment: Drug: dorzolamide/timolol; Drug: latanoprost

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)

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 137-070
    • Seoul St. Mary'S Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; Latanoprost first, then Dorzolamide/Timolol Patients first on Latanoprost eyedrops once a day, then on Dorzolamide/Timolol twice a day	Drug: dorzolamide/timolol; dorzolamide/timolol fixed combination eyedrop, 2 times a day; Other Names: Cosopt; Drug: latanoprost; compare with dorzolamide/timolol fixed combination eyedrop one time a day; Other Names: Xalatan
Active Comparator: Arm 2; Dorzolamide/Timolol first, then Latanoprost Patients first on Dorzolamide/Timolol eyedrops twice a day, then on Latanoprost eyedrops once a day	Drug: dorzolamide/timolol; dorzolamide/timolol fixed combination eyedrop, 2 times a day; Other Names: Cosopt; Drug: latanoprost; compare with dorzolamide/timolol fixed combination eyedrop one time a day; Other Names: Xalatan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraocular Pressure (IOP), Period 1	IOP (mean IOP) after 4 weeks of treatment	4 weeks
Intraocular Pressure (IOP), Period 2	IOP (mean IOP) after treaemt from week 8 to week 12	12 weeks
Blood Pressure (BP), Period 1	systolic and diastolic BP at 4 weeks after use of eyedrops	4 weeks
Blood Pressure (BP), Period 2	systolic and diastolic BP measured after treaemt from week 8 to week 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Perfusion Pressure (OPP), Period 1	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	4 weeks
OPP, Period 2	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 OPP after treaemt from week 8 to week 12	12 weeks

Collaborators and Investigators

• Sponsor: The Catholic University of Korea
• Collaborators: Seoul St. Mary's Hospital
• Investigators: Principal Investigator: Chan Kee Park, M.D., PhD., The Catholic University of Korea

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: July 26, 2010
• First Submitted That Met QC Criteria: August 4, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: December 12, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Normal tension glaucoma
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Optic Nerve Diseases; Glaucoma; Low Tension Glaucoma; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Pharmaceutical Solutions; Ophthalmic Solutions; Timolol; Dorzolamide; Latanoprost
• Other Study ID Numbers: cosopt-IOP/OPP