Effects of Cosopt on IOP and on Ocular Diastolic Perfusion Pressure

A Pilot Study on the Effects of Cosopt on IOP Lowering and Ocular Diastolic Perfusion Pressure in Patients Not Controlled With Xalatan Monotherapy

Hypothesis: Studies suggest that patients with low diastolic velocity and high resistivity index in the ophthalmic artery had more progressive visual fields, the investigators hypothesize therefore that addition of Cosopt to Latanoprost could improve ocular diastolic perfusion pressure (ODPP).

Objective: To evaluate the effects of Cosopt on ODPP in patients not adequately controlled with latanoprost alone.

Study Overview

• Status: Unknown
• Conditions: Glaucoma
• Intervention / Treatment: Drug: Xalatan+Cosopt; Drug: Xalatan

Detailed Description

Fifty patients with primary open angle glaucoma (POAG) treated with Xalatan for whom the monotherapy was not sufficient to achieve the target IOP, will be included in the study. Non responders were defined when IOP was > 20 mmHg or if the IOP reduction was less than 25% from the baseline IOP. Patients will be classified as having POAG when they had a typical glaucomatous visual field and/or a typical abnormal optic nerve head, open angle at gonioscopy, IOP > 21 mmHg with no treatment and no clinically apparent secondary cause for their glaucoma (EGS guidelines).

Visual fields will be assessed by an Humphrey Field Analyzer 750 (HFA, Humphrey, Inc, CA, USA), 24-2 SITA (Swedish Interactive Threshold Algorithm) standard. A glaucomatous visual field defect was defined as: 1) three adjacent points depressed by 5 dB, with one of the points depressed by at least 10 dB; 2) two adjacent points depressed by 10 dB; or 3) a 10 dB difference across the nasal horizontal meridian in two adjacent points. None of the points could be edge points unless immediately above or below the nasal horizontal meridian. In addition, visual field testing was considered reliable only when false-negative responses were less than 30% and fixation losses were less than 20% on HFA.

The abnormal optic nerve head classification was based on the presence of an optic rim notch or of diffuse / generalized loss of optic rim tissue, vertical cup/disc diameter ratio asymmetry unexplained by side differences in optic disc size, disc haemorrhage.

In each centre, patient's recruitment will start as soon as the ethical committee will approve the protocol. Each sites will recruit 10 patients (5 + 5).

Cosopt will be added to Xalatan when Xalatan is effective but not sufficient to reach the target pressure (Add group) (n = 25), while when Xalatan is effective and sufficient to reach the target pressure no other medication will be added (control group) (n = 25).

(EGS guidelines: Target pressure is a subjective value that none is able to assess (until now!). Efficacy of a drug: when the medication can decrease IOP as described in the phase three of their clinical trial. Not sufficient: when the medication is effective but is not able to reach the target IOP.)

Each patient will be submitted to three different visits:

• Baseline visit: Systemic Pressure, IOP, VF, HRF, Visual Acuity, ophthalmic examination with corneal central thickness (CCT)
• Visit at 1 month: Systemic Pressure , IOP, Visual Acuity, ophthalmic examination
• Visit at 3 months: Systemic Pressure, IOP , HRF, Visual Acuity, ophthalmic examination (+ CCT) ODPP will be calculated by: "systemic diastolic pressure - IOP" at each session.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Teresa Rolle, MD; Phone Number: 00390115666032; Email: teresa.rolle@unito.it

Study Locations

• Italy
  • Bari, Italy, 70124
    • University of Bari
    • Contact: Michele Vetrugno, MD; Phone Number: 00 39 080 5592525; Email: : m.vetrugno@oftalmo.uniba.it
    • Sub-Investigator: Michele Vetrugno, MD
  • Chieti, Italy, 66100
    • University of Chieti
    • Contact: Marco Ciancaglini, MD; Phone Number: 0039 0871 358410; Email: m.ciancaglini@unich.it
    • Sub-Investigator: Marco Ciancaglini, MD
  • Genova, Italy, 16132
    • University of Genova
    • Contact: Michele Iester, MD; Phone Number: 00 39 010 3538469; Email: iester@unige.it
    • Sub-Investigator: Michele Iester, MD
  • Siena, Italy, 53100
    • University of Siena
    • Contact: Paolo Frezzotti, MD; Phone Number: 00 39 0577 233360; Email: frezzottip@unisi.it
    • Sub-Investigator: Paolo Frezzotti, MD
  • Turin, Italy, 10143
    • University of Turin
    • Contact: Teresa Rolle, MD; Phone Number: 00390115666032; Email: teresa.rolle@unito.it
    • Principal Investigator: Teresa Rolle, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• POAG patients with a pattern deviation score (or its equivalent) ranging from 2.5 dB to 6.0 dB will be included in the study. This will ensure that patients with early/mid-stage glaucoma will be homogeneously collected; avoids advanced glaucoma in which OBF may behave as a different disease state.
• Best-corrected visual acuity will be of 0.5 or better with an ametropia <5D - Dioptric transparency, non smokers.
• Age will be between 45 and 65 years.

Exclusion Criteria:n

• Normal tension glaucoma, ocular hypertension, cardiovascular and/or metabolic diseases (known to affect blood flow, as diabetes and polycythemia)
• Visual field defects other than glaucoma; use of vasoactive and/or anti-hypertensive drugs (systemic beta-blocker), use of acetazolamide
• Hypersensibility and/or contraindications to any of the molecules studied
• Previous ocular surgery
• Pregnant or nursing women and use of one of drugs for erectile dysfunction

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Xalatan+Cosopt; Cosopt will be added to Xalatan when Xalatan is effective but not sufficient to reach the target pressure (Add group) (n = 25)	Drug: Xalatan+Cosopt; Xalatan ophthalmic solution one drop at 10pm + Cosopt ophthalmic solution one drop at 8am and one drop at 8 pm; Drug: Xalatan; Xalatan ophthalmic solution one drop at 10pm
Active Comparator: Xalatan; when Xalatan is effective and sufficient to reach the target pressure no other medication will be added (control group) (n = 25)	Drug: Xalatan; Xalatan ophthalmic solution one drop at 10pm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effects of Cosopt on ODPP in patients not adequately controlled with latanoprost alone	baseline, at 1 and 3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the effects of Cosopt on IOP lowering in patients not adequately controlled with latanoprost alone.	baseline, at 1 and 3 months

Collaborators and Investigators

• Sponsor: University of Turin, Italy
• Investigators: Principal Investigator: Teresa Rolle, MD, Assistent Professor, University of Turin, Department of Clinical Physiopathology, Section of Ophthalmology, Eye Clinic; Principal Investigator: Teresa Rolle, MD, Assistent Professor, University of Turin, Department of Clinical Physiopathology-Section of Ophthalmology-Eye Clinic

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Anticipated): June 1, 2009
• Study Completion (Anticipated): July 1, 2009

Study Registration Dates

• First Submitted: November 21, 2008
• First Submitted That Met QC Criteria: November 21, 2008
• First Posted (Estimate): November 24, 2008

Study Record Updates

• Last Update Posted (Estimate): November 25, 2008
• Last Update Submitted That Met QC Criteria: November 24, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Intraocular pressure; Glaucoma; Ocular diastolic perfusion pressure; Dorzolamide/timolol Fixed combination; Heidelberg Retina Flowmeter
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Pharmaceutical Solutions; Ophthalmic Solutions; Latanoprost
• Other Study ID Numbers: COS16102007