The Effects of Cosopt® Vs Xalacom® on Ocular Hemodynamics and Intraocular Pressure (IOP) in Primary Open-angle Glaucoma (POAG) (Xal-Cos)

A Comparative Analysis of the Effects of Cosopt® Versus Xalacom® on Ocular Hemodynamics and Intraocular Pressure in Patients With Primary Open-angle Glaucoma

Both Cosopt® and Xalatan® plus Timoptic® will significantly lower IOP, however only Cosopt® will demonstrate positive hemodynamic effects. The clinical significance of this will be investigated by examining the ophthalmic and short posterior ciliary arteries to determine the blood supply to the optic nerve head, the site of damage in glaucoma

Study Overview

• Status: Withdrawn
• Conditions: Ocular Hypertension; Open-Angle Glaucoma
• Intervention / Treatment: Drug: Dorzolamide+Timolol Maleate0.5%; Drug: Latanoprost+Timolol Maleate0.5%+Lytears

Detailed Description

Background and Rationale

Apoptosis of retinal ganglion cell has been considered as the most plausible pathogenic mechanism of glaucoma. Apoptosis can be caused by neurotrophic factor withdrawal or glutamate release and both of them are triggered by elevated intraocular pressure (IOP) and ischemia simultaneously or separately.

The topical carbonic anhydrase inhibitor, Dorzolamide (Trusopt*), has recently been approved for chronic use in the treatment of glaucoma. The ocular hypotensive effects of this topical carbonic anhydrase inhibitor seem likely to produce the same results as *-adrenergic antagonists. Systemic carbonic anhydrase inhibitors are known to have vasodilatory effects (Maren,1987). Rassam S.M.B., Patel V. and Kohner E.M. (1993) have concluded that acetazolamide causes an increase in retinal blood flow in the human retinal circulation. It has also been demonstrated that Trusopt* increases retinal circulation as measured by scanning laser ophthalmoscopy (SLO) (Harris, Arend, Martin, 1996). Furthermore, Trusopt increases arteriovenous passage (AVP) time and improves contrast sensitivity in normal tension glaucoma patients (Harris, 1999).

Cosopt* (dorzolamide hydrochloride-timolol maleate ophthalmic solution) is combination of a topical carbonic anhydrase inhibitor and a topical beta-adrenergic receptor blocking agent. Each of these two components reduces intraocular pressure. The IOP-reducing effect of Cosopt b.i.d. was greater (1-3 mm Hg) than that of monotherapy with either 2.0 % dorzolamide t.i.d. or 0.5 % timolol b.i.d. The IOP-lowering effect of Cosopt* b.i.d. was approximately 1 mm Hg less than that of concomitant therapy with 2.0% dorzolamide t.i.d. and 0.5 % timolol b.i.d. A previous study showed that the retinal circulation (AVP time) was significantly accelerated after replacing Timoptic* with Cosopt* in glaucoma patients (Harris, 1999).

Latanoprost (Xalatan*) is a prostaglandin F2* analogue which is believed to reduce IOP by increasing the outflow of aqueous humor. The retinal vascular effects of Latanoprost, however, remain unclear. While some studies have shown PGF2* to induce constriction in bovine isolated aqueous veins (Nielsen 1996), other studies have been unable to demonstrate an effect on retrobulbar flow velocities (Drance 1996). It is possible that vasoconstrictive properties of the drug may produce a negative impact on previously ischemic retinal tissue or at best no change.

In a recent study comparing Trusopt® with Xalatan® some very encouraging results emerged, AVP time was significantly reduced with Trusopt®, but not with Xalatan® despite the fact that Xalatan® increases perfusion pressure (due to IOP) more than Trusopt®. This is the strongest evidence so far of a pressure independent effect of Trusopt® on ocular blood flow.

Objectives

• To compare the IOP efficacy of Cosopt® and Xalacom® on IOP.
• To determine the perfusion pressure effect of Cosopt® and Xalacom®.
• To determine the blood flow effect of the two drugs on the ophthalmic, central retinal and short posterior ciliary arteries, using Color Doppler Imaging (CDI).

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Kfar Saba, Israel
    • Meir Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18 years of age or greater.
2. Patient signed an informed consent agreement.
3. Corrected visual acuity of 6/12 or better:
4. Characteristic glaucomatous visual-field loss and optic nerve head damage in one or both eyes.
5. Either IOP measurements ≥21 mmHg in the 3 months prior to study entry or IOP ≥ 21 mmHg at the end of the washout period
6. Patient on ≥1 IOP reducing agents. -

Exclusion Criteria:

1. Past history of ocular diseases (other than OAG / Cataract / Refractive error).
2. Past history of orbital/ocular surgery or trauma.
3. Receiving ≥ 3 IOP reducing agents.
4. Receiving agents known to produce significant cardiovascular, respiratory, renal or hepatic side effects.
5. Personal history of respiratory disease such as asthma, emphysema or other chronic obstructive pulmonary disease.
6. Personal history of congestive heart failure.
7. Personal history of bradycardia or 2nd and 3rd degree AV block.
8. Known allergy to sulfa.
9. Women who are pregnant or nursing.
10. Women who of child bearing age who are planning to become pregnant within one month after study completion.
11. Receiving Levitra, Viagra, Cialis or other erectile dysfunction drugs.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: 1; Cosopt* b. i. d. (dosed morning and bedtime) will be administered topically	Drug: Dorzolamide+Timolol Maleate0.5%; Cosopt* b. i. d.; Other Names: Cosopt
ACTIVE_COMPARATOR: 2; Xalacom* q.d.(dosed bedtime) and placebo vehicle q.d. (dosed morning) topically in the other group	Drug: Latanoprost+Timolol Maleate0.5%+Lytears; Xalacom* QHS; Other Names: Xalacom* QHS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ocular hemodynamics as measured by Color Doppler imaging	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Intraocular pressure as measured by Goldmann applanation tonometry	3 Years

Collaborators and Investigators

• Sponsor: Meir Medical Center
• Investigators: Principal Investigator: Adi Abulafia, MD, Meir Medical Center, Tel Aviv University

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (ANTICIPATED): December 1, 2011
• Study Completion (ANTICIPATED): June 1, 2012

Study Registration Dates

• First Submitted: December 9, 2008
• First Submitted That Met QC Criteria: December 29, 2008
• First Posted (ESTIMATE): December 30, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 16, 2012
• Last Update Submitted That Met QC Criteria: March 15, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Ocular hypertension; POAG; Cosopt; Ocular Blood flow; Ocular hemodynamics; Xalacom
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; 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; Maleic acid; Latanoprost
• Other Study ID Numbers: 0155-08-MMC