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

This study has been withdrawn prior to enrollment.
(no participants recruded.)
Sponsor:
Information provided by:
Meir Medical Center
ClinicalTrials.gov Identifier:
NCT00815373
First received: December 9, 2008
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

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 Intervention
Open-Angle Glaucoma
Ocular Hypertension
Drug: Dorzolamide+Timolol Maleate0.5%
Drug: Latanoprost+Timolol Maleate0.5%+Lytears

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Meir Medical Center:

Primary Outcome Measures:
  • Ocular hemodynamics as measured by Color Doppler imaging [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Intraocular pressure as measured by Goldmann applanation tonometry [ Time Frame: 3 Years ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: December 2008
Estimated Study Completion Date: June 2012
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Xalacom* QHS

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).
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00815373

Locations
Israel
Meir Medical Center
Kfar Saba, Israel
Sponsors and Collaborators
Meir Medical Center
Investigators
Principal Investigator: Adi Abulafia, MD Meir Medical Center, Tel Aviv University
  More Information

No publications provided

Responsible Party: Adi Abulafia, MD, Meir Medical Center, Kfar Saba, Affiliated to Tel Aviv University Israel
ClinicalTrials.gov Identifier: NCT00815373     History of Changes
Other Study ID Numbers: 0155-08-MMC
Study First Received: December 9, 2008
Last Updated: March 15, 2012
Health Authority: Israel: The Israel National Institute for Health Policy Research and Health Services Research

Keywords provided by Meir Medical Center:
Ocular Blood flow
Ocular hypertension
POAG
Ocular hemodynamics
Xalacom
Cosopt

Additional relevant MeSH terms:
Glaucoma
Glaucoma, Open-Angle
Hypertension
Ocular Hypertension
Cardiovascular Diseases
Eye Diseases
Vascular Diseases
Maleic acid
Timolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-Antagonists
Anti-Arrhythmia Agents
Antihypertensive Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014