Glaucoma
Conditions
Keywords
glaucoma, trabeculectomy, intraocular pressure
Brief summary
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
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.
Interventions
DRUGTrabeculectomy with preoperative Diamox/DexaEDO treatment
Filtrating glaucoma surgery, preoperative treatment with Diamox (acetazolamide) 28 day prior surgery. DexaEDO (dexamethasone) 7 days prior surgery
DRUGTrabeculectomy with preoperative Cosopt S treatment
Filtrating glaucoma surgery, preoperative treatment with Cosopt S (dorzolamide/timolol) 28 day prior surgery.
Sponsors
Katrin Lorenz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intraocular Pressure (IOP) (ΔIOP) Three Months After Trabeculectomy in Comparison to the Mean Preoperative IOP | 12 weeks | Change in IOP (ΔIOP) three months after trabeculectomy in comparison to the mean preoperative IOP at one day prior surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Necessary 5-Fluorouracil (5FU) Injections | 12 weeks | Number of post-operative necessary 5-Fluorouracil (5FU) injections at week 12 |
| Ocular Hypotension Rate | 24 weeks | Ocular hypotension rate (0-5 mmHg of the study eye) indicated by the number of patients with ocular hypertension |
| Change in IOP Between Visit 1 and 2 | 28 days | 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. |
| Number of Needling | 12 weeks | number of patients requirering needling |
| Change in Quality of Life | 12 weeks | 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. |
| Change in Conjunctival Redness | 24 weeks | 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. |
| Number of Suture Lyses | week 12 | Number of suture lyses at visit 5 (week 12 after surgery) |
| Filtration Bleb Classification | 24 weeks | 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. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diamox/DexaEDO Patients receive Diamox (oral acetazolamide) starting 28 days preoperatively. 7 days preoperatively DexaEDO (dexamethasone) eyedrops without preservatives are applied additionally.
Trabeculectomy: Filtrating glaucoma surgery, preoperative treatment will be assessed. | 32 |
| Cosopt S Patients receive Cosopt S (dorzolamide/timolol) eye drops starting 28 days preoperatively
Trabeculectomy: Filtrating glaucoma surgery, preoperative treatment will be assessed. | 30 |
| Total | 62 |
Baseline characteristics
| Characteristic | Cosopt S | Diamox/DexaEDO | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 18 Participants | 15 Participants | 33 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 17 Participants | 29 Participants |
| Age, Continuous | 65.8 years STANDARD_DEVIATION 8.82 | 64.2 years STANDARD_DEVIATION 10.51 | 64.98 years STANDARD_DEVIATION 9.68 |
| Region of Enrollment Germany | 30 Participants | 32 Participants | 62 Participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 31 Participants |
| Sex: Female, Male Male | 18 Participants | 13 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 31 | 23 / 28 |
| serious Total, serious adverse events | 4 / 31 | 3 / 28 |
Outcome results
Primary
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
Time frame: 12 weeks
Population: In total 62 patients were randomized, 30 to COSOPT-S®, 32 to DIAMOX+Dexa edo® (intention-to-treat (ITT) population. Per-protocol (PP) population (treated \>8 days and did not take any medication that interfered with the study): n=58 patients: 27 p. in COSOPT-S®, 31 p. in DIAMOX+Dexa edo®. Analysis population: patients who completed the study n=53
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diamox/DexaEDO | Change in Intraocular Pressure (IOP) (ΔIOP) Three Months After Trabeculectomy in Comparison to the Mean Preoperative IOP | 8.30 mmHg |
| Cosopt S | Change in Intraocular Pressure (IOP) (ΔIOP) Three Months After Trabeculectomy in Comparison to the Mean Preoperative IOP | 8.12 mmHg |
Secondary
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.
Time frame: 24 weeks
Population: ITT population
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 1 | moderate | 13 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 2 | none | 9 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 1 | mild | 13 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 2 | mild | 15 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 1 | severe | 4 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 1 | none | 1 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 2 | severe | 1 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 1 | very severe | 1 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 2 | very severe | 0 Participants |
| Diamox/DexaEDO | Change in Conjunctival Redness | Visit 2 | moderate | 2 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 2 | very severe | 0 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 1 | none | 0 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 1 | mild | 12 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 1 | moderate | 15 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 1 | severe | 3 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 1 | very severe | 0 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 2 | none | 7 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 2 | mild | 16 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 2 | moderate | 4 Participants |
| Cosopt S | Change in Conjunctival Redness | Visit 2 | severe | 0 Participants |
Secondary
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.
Time frame: 28 days
Population: PP Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Diamox/DexaEDO | Change in IOP Between Visit 1 and 2 | 8.19 mmHg |
| Cosopt S | Change in IOP Between Visit 1 and 2 | 1.88 mmHg |
Secondary
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.
Time frame: 12 weeks
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diamox/DexaEDO | Change in Quality of Life | 80.71 scores on a scale | Standard Deviation 11.64 |
| Cosopt S | Change in Quality of Life | 79.48 scores on a scale | Standard Deviation 15.44 |
Secondary
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.
Time frame: 24 weeks
Population: PP Population
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diamox/DexaEDO | Filtration Bleb Classification | 2 mm | 14 Participants |
| Diamox/DexaEDO | Filtration Bleb Classification | Flat | 3 Participants |
| Diamox/DexaEDO | Filtration Bleb Classification | 1 mm | 5 Participants |
| Diamox/DexaEDO | Filtration Bleb Classification | Missing | 5 Participants |
| Diamox/DexaEDO | Filtration Bleb Classification | at least 3 mm | 4 Participants |
| Cosopt S | Filtration Bleb Classification | Missing | 1 Participants |
| Cosopt S | Filtration Bleb Classification | at least 3 mm | 2 Participants |
| Cosopt S | Filtration Bleb Classification | 2 mm | 17 Participants |
| Cosopt S | Filtration Bleb Classification | 1 mm | 5 Participants |
| Cosopt S | Filtration Bleb Classification | Flat | 2 Participants |
Secondary
Number of Necessary 5-Fluorouracil (5FU) Injections
Number of post-operative necessary 5-Fluorouracil (5FU) injections at week 12
Time frame: 12 weeks
Population: PP Population (n=58)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Diamox/DexaEDO | Number of Necessary 5-Fluorouracil (5FU) Injections | 5.14 number of injections | Standard Deviation 2.61 |
| Cosopt S | Number of Necessary 5-Fluorouracil (5FU) Injections | 5.26 number of injections | Standard Deviation 3.13 |
Secondary
Number of Needling
number of patients requirering needling
Time frame: 12 weeks
Population: Patients of the PP population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diamox/DexaEDO | Number of Needling | 0 Participants |
| Cosopt S | Number of Needling | 2 Participants |
Secondary
Number of Suture Lyses
Number of suture lyses at visit 5 (week 12 after surgery)
Time frame: week 12
Population: Intention-to- treat population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Diamox/DexaEDO | Number of Suture Lyses | 0 suture lyses | 11 Participants |
| Diamox/DexaEDO | Number of Suture Lyses | 1-2 suture lyses | 10 Participants |
| Diamox/DexaEDO | Number of Suture Lyses | 3-4 suture lyses | 7 Participants |
| Cosopt S | Number of Suture Lyses | 0 suture lyses | 10 Participants |
| Cosopt S | Number of Suture Lyses | 1-2 suture lyses | 12 Participants |
| Cosopt S | Number of Suture Lyses | 3-4 suture lyses | 5 Participants |
Secondary
Ocular Hypotension Rate
Ocular hypotension rate (0-5 mmHg of the study eye) indicated by the number of patients with ocular hypertension
Time frame: 24 weeks
Population: PP Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Diamox/DexaEDO | Ocular Hypotension Rate | 5 Participants |
| Cosopt S | Ocular Hypotension Rate | 3 Participants |