COSOPT-S® Treatment Versus Acetazolamide Before Trabeculectomy

Investigation of the Efficacy and Safety of Preoperative Intraocular Pressure (IOP) Reduction With Preservative-free COSOPT-S® (Dorzolamide/Timolol, MSD) Eye Drops Versus Oral Acetazolamide and Dexamethasone Eye Drops

The most common cause of post-trabeculectomy filtration failure is postoperative scarring. Long-term preoperative treatment with local antiglaucoma agents containing preservatives has an increased risk of post-operative scarring of the filtration bleb. Therefore many surgeons prepare their patients for planned trabeculectomy by discontinuing local antiglaucoma drugs, controlling IOP with oral acetazolamide, and treating the eye with local steroids.

Preservative-free COSOPT-S® eye drops b.i.d now provide a possibility to reduce IOP preoperatively with the aim of avoiding postoperative excessive scarring and the known adverse effects of oral acetazolamide while achieving comparable IOP reduction and long-term outcomes.

This study will investigate comparability (non-inferiority) of medical benefits of two different IOP lowering pharmaceutical interventions prior to trabeculectomy comparing COSOPT-S® bid to oral acetazolamide plus dexamethasone.

Study Overview

• Status: Completed
• Conditions: Glaucoma
• Intervention / Treatment: Drug: Trabeculectomy with preoperative Diamox/DexaEDO treatment; Drug: Trabeculectomy with preoperative Cosopt S treatment

Detailed Description

The most common cause of post-trabeculectomy filtration failure is postoperative scarring. Long-term preoperative treatment with local antiglaucoma agents containing preservatives has an increased risk of post-operative scarring of the filtration bleb. Therefore many surgeons prepare their patients for planned trabeculectomy by discontinuing local antiglaucoma drugs, controlling IOP with oral acetazolamide, and treating the eye with local steroids.

Preservative-free COSOPT-S® eye drops b.i.d now provide a possibility to reduce IOP preoperatively with the aim of avoiding postoperative excessive scarring and the known adverse effects of oral acetazolamide while achieving comparable IOP reduction and long-term outcomes.

This study will investigate comparability (non-inferiority) of medical benefits of two different IOP lowering pharmaceutical interventions prior to trabeculectomy comparing COSOPT-S® bid to oral acetazolamide plus dexamethasone.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55131
    • Clinical Trial Site, Department of Ophthalmology, University Medical Center Johannes Gutenberg University Mainz

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:

• Male or female patients aged 18 years or older
• Caucasian
• A clinical diagnosis of open angle glaucoma, pseudoexfoliation or pigment dispersion glaucoma, or ocular hypertension in one or both eyes
• Planned trabeculectomy
• Previous treatment with antiglaucoma agents containing preservatives for at least one month
• Best corrected visual acuity of 20/800 or better in the study eye

Exclusion Criteria:

• Secondary glaucoma except pseudoexfoliation glaucoma and pigmentary glaucoma
• Current ocular infection, i.e. conjunctivitis or keratitis
• Any abnormality preventing reliable applanation tonometry
• Intraocular surgery or laser treatment within the past three months
• History of surgery involving the conjunctiva
• History of cataract surgery with sclerocorneal approach
• Subject is allergic to sulfonamides
• Reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease
• Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, cardiogenic shock
• Severe renal dysfunction (CrCl < 30 ml/min) or hyperchloraemic acidosis
• Depressed blood levels of sodium and / or potassium
• Marked kidney and liver disease or dysfunction, gout, suprarenal gland failure, hypercalciuria or nephrocalcinosis
• History of hypersensitivity to the investigational medicinal products or to any drug

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Diamox/DexaEDO; Patients receive Diamox (oral acetazolamide) starting 28 days Prior to trabeculectomy. 7 days preoperatively DexaEDO (dexamethasone) eyedrops without preservatives are applied additionally. Patient will undergo trabeculectomy.	Drug: Trabeculectomy with preoperative Diamox/DexaEDO treatment; Filtrating glaucoma surgery, preoperative treatment with Diamox (acetazolamide) 28 day prior surgery. DexaEDO (dexamethasone) 7 days prior surgery; Other Names: Filtrating glaucoma surgery
Experimental: Cosopt S; Patients receive Cosopt S (dorzolamide/timolol) eye drops starting 28 days before trabeculectomy.	Drug: Trabeculectomy with preoperative Cosopt S treatment; Filtrating glaucoma surgery, preoperative treatment with Cosopt S (dorzolamide/timolol) 28 day prior surgery.; Other Names: Filtrating glaucoma surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Intraocular Pressure (IOP) (ΔIOP) Three Months After Trabeculectomy in Comparison to the Mean Preoperative IOP	Change in IOP (ΔIOP) three months after trabeculectomy in comparison to the mean preoperative IOP at one day prior surgery	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Needling	number of patients requirering needling	12 weeks
Number of Necessary 5-Fluorouracil (5FU) Injections	Number of post-operative necessary 5-Fluorouracil (5FU) injections at week 12	12 weeks
Ocular Hypotension Rate	Ocular hypotension rate (0-5 mmHg of the study eye) indicated by the number of patients with ocular hypertension	24 weeks
Change in IOP Between Visit 1 and 2	Change in IOP between Visit 1 (Screening visit 16 to 28 day prior trabeculectomy) and Visit 2 (1 day before trabeculectomy). Outcome shows mean of differences and 95% confidence intervall.	28 days
Filtration Bleb Classification	Filtration bleb classification (Grehn) in both Groups 1 week, 4 weeks, 12 weeks and 24 week after surgery. For classification the following criteria were evaluated and scored as described below: vascularisation (0=None, 1=mild, 2=a few corkscrew vessels); identifiability (0=no borders to sides; 1=demarcation nasally or temporally; 2= demarcation to both sides; 3= encapsulated); Thickness (0= a least 3mm; 1=2mm; 2= 1mm; 3=flat); Microcysts (0=no; 1= yes); Transparency (0= highly transparent; 2=moderate; 2=not transparent); Mobility (0= yes; 1= no); Leakage (0=yes, 1=no) For the change in the filtration bleb classification (only thickness at visit 5/week 12 mentioned below) descriptive statistics were presented only.	24 weeks
Change in Quality of Life	Change in quality of life measure by a certified National Eye Institute Visual Functioning Questionnaire containing 25 questions (NEI VFQ-25).Patients tick a score at every question to present their visual functioning (usually from 1-5 or 1-6 in which 1 is best and 6 worse). Every single item/score is transformed to a scale between 0 and 100 (0 best, 100 worse). For the total score, the mean of all transformed scores/items is calculated. NEI VFQ 25 Quality of Life Questionnaire composite score at V5 (week 12 after surgery). Outcome shows mean of differences and 95% confidence intervall.	12 weeks
Change in Conjunctival Redness	Conjunctival redness (ORA Scale) evaluated from 16 up to 28 days (time window) prior surgery and 1 day prior surgery. The investigator compares patient's study eye with a set of reference photos showing various degrees of redness. Redness was scored on a scale of "none", "mild", "moderate", "severe" and "very severe". Absolute and relative frequencies of visit 1 and 2 were compared descriptively.	24 weeks
Number of Suture Lyses	Number of suture lyses at visit 5 (week 12 after surgery)	week 12

Collaborators and Investigators

• Sponsor: Katrin Lorenz
• Investigators: Principal Investigator: Katrin Lorenz, MD, Johannes Gutenberg University Mainz

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: August 20, 2010
• First Submitted That Met QC Criteria: October 25, 2010
• First Posted (Estimate): October 26, 2010

Study Record Updates

• Last Update Posted (Actual): August 1, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: intraocular pressure; glaucoma; trabeculectomy
• Additional Relevant MeSH Terms: Eye Diseases; Ocular Hypertension; Glaucoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: 35131; EUDRA CT 2010-019975-30