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

Ocular Hypertension Clinical Trial

— Xal-Cos  

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00815373
• Other study ID #: 0155-08-MMC
• Status: Withdrawn
• Phase: N/A
• First received: December 9, 2008
• Last updated: March 15, 2012
• Start date: December 2008
• Est. completion date: June 2012

Study information

• Verified date: March 2012
• Source: Meir Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: The Israel National Institute for Health Policy Research and Health Services Research
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Glaucoma
• Glaucoma, Open-Angle
• Ocular Hypertension
• Open-Angle Glaucoma

Intervention

Drug:
• Dorzolamide+Timolol Maleate0.5%
Cosopt* b. i. d.
• Latanoprost+Timolol Maleate0.5%+Lytears
Xalacom* QHS

Locations

Country	Name	City	State
Israel	Meir Medical Center	Kfar Saba

Sponsors (1)

Lead Sponsor	Collaborator
Meir Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ocular hemodynamics as measured by Color Doppler imaging		3 years	No
Secondary	Intraocular pressure as measured by Goldmann applanation tonometry		3 Years	No