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

Sponsor

Meir Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00815373

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma Ocular Hypertension	Drug: Dorzolamide+Timolol Maleate0.5% Drug: Latanoprost+Timolol Maleate0.5%+Lytears	N/A

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Official Title:

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

Study Start Date :

Dec 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2011

Anticipated Study Completion Date :

Jun 1, 2012

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Ocular hemodynamics as measured by Color Doppler imaging [3 years]

Secondary Outcome Measures

Intraocular pressure as measured by Goldmann applanation tonometry [3 Years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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