COSOPT-S® Treatment Versus Acetazolamide Before Trabeculectomy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Glaucoma

Intervention / Treatment
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* Drug: Trabeculectomy with preoperative Diamox/DexaEDO treatment
* Drug: Trabeculectomy with preoperative Cosopt S treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Diamox/DexaEDO<br>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<br>* Filtrating glaucoma surgery, preoperative treatment with Diamox (acetazolamide) 28 day prior surgery. DexaEDO (dexamethasone) 7 days prior surgery<br>* Other names: Filtrating glaucoma surgery;|
| Experimental: Cosopt S<br>Patients receive Cosopt S (dorzolamide/timolol) eye drops starting 28 days before trabeculectomy. | Drug: Trabeculectomy with preoperative Cosopt S treatment<br>* Filtrating glaucoma surgery, preoperative treatment with Cosopt S (dorzolamide/timolol) 28 day prior surgery.<br>* Other names: Filtrating glaucoma surgery;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glaucoma, trabeculectomy, intraocular pressure