Ignite Creation Date:
2024-05-05 @ 5:28 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00468429
Status:
UNKNOWN
Last Update Posted:
2007-06-04
First Post:
2007-04-30
Brief Title:
Subconjunctival Bevacizumab to Prevent Bleb Failure After Glaucoma Filtration Surgery
Sponsor:
Grewal Eye Institute
Organization:
Grewal Eye Institute
Study Overview
Official Title:
Comparative Study of the Safety and Effectiveness Between Off-Label Subconjunctival Bevacizumab and Mitomycin C in Glaucoma Filtering Surgery
Status:
UNKNOWN
Status Verified Date:
2007-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study analyzes the safety and efficacy of off-label Subconjunctival Injection of bevacizumab Avastin versus 002 mitomycin C MMC for preventing bleb failure following glaucoma filtration surgery
Detailed Description:
Glaucoma Filtration Surgery GFS remains the definitive surgical management for elevated IOL uncontrolled by medical management Bleb failure is a major factor limiting the longterm success of trabeculectomy surgery Bleb failure involves vascularization with fibroblast migration and eventual scarring of the fistula tract Vascular Endothelial Growth Factor VEGF is a unique mitogen specific to vascular endothelial cells and the signal cascade leading to fibroblast migration and proliferation involves dynamic interaction between many proteins Blocking the neovascular signal cascade with anti-VEGF molecules like Bevacizumab may lead to a decrease in fibroblast proliferation by decreasing the supply of mitogenic cytokines such as fibroblast growth factor FGF carried in by new vessel formation and decreasing the known synergism that exists between VEGF and fibroblast growth factor FGF The study is designed as an off-label randomized parallel comparative study Patients who meet the inclusionexclusion criteria and sign the informed consent will be included After enrollment patients will be randomized into two groups trabeculectomy with off-label subconjunctival bevacizumab or trabeculectomy with mitomycin-CThis study aims to compare the safety and effectiveness of off-label subconjunctival bevacizumab and subtenon Mitomycin C in glaucoma filtration surgery GFS The primary endpoint is to prove the effectiveness via the reduction of IOP and grading of bleb photographs according to the Moorfields Bleb Grading Protocol and the secondary endpoint is to prove the safety via the incidence of complications and adverse events
Procedure Surgical technique Trabeculectomy will be performed after the administration of retrobulbar or peribulbar anesthesia with lidocaine For the limbus-based procedure a bridle suture 4-0 silk will be placed under the superior rectus muscle tendon and the conjunctiva and Tenons capsule will be incised in the superior quadrant 8 to 10 mm posterior to the surgical limbus The conjunctiva and Tenons capsule will be dissected anterior to the limbus Meticulous hemostasis will be achieved with bipolar cautery In cases randomized to MMC usage a cellulose sponge approximately 6 12 mm 1 mm soaked with mitomycin C 02 mgml will be applied over the intended site of the scleral flap for 1 to 3 minutes The duration of mitomycin C application will be based on the preoperative evaluation of each patients risk factors for failure Copious irrigation with balanced salt solution will be performed to wash away residual MMC A ½ to 23 thickness square scleral flap approximately 35 35 mm will be then dissected into the clear cornea After resection of an anterior trabecular block approximately 25 1 mm an iridectomy will be performed The scleral flap will be sutured with two or three 10-0 nylon sutures at its corners The conjunctiva and Tenons capsule will be closed in a single continuous layer with 8-0 Vicryl suture In the subjects randomized to receive Injection Bevacizumab 005 ml of reconstituted bevacizumab drug 125 mg will be injected subconjunctivally adjacent to the bleb Atropine eye ointment will be placed in the fornix and the eye will be patched In the early postoperative period all patients will be treated with topical corticosteroids four times daily for two weeks which will be tapered-off slowly over six to eight weeks Suture-lysis with argon laser will be performed under topical anesthesia when in the opinion of the surgeon filtration is judged to be too low and the IOP too high for the patient to meet the target pressure
Preparation of the Drug
Bevacizumab Avastin Avastin is available in a sterile vial 100 mg in 4 ml preservative free and in order to ensure safety the vial injection will be administered within one day
Subconjunctival Injections 125mg drug in 005ml will be given at the end of the surgery adjacent to the bleb raised using a single-use 30-gauge needle and a tuberculin syringe
Follow-Up The following demographic and clinical data will be extracted from the medical records of eligible patients race age of the patient at the time of surgery gender eye laterality preoperative visual acuity refractive error average of IOP readings during three months before surgery number of medications recorded during the three months preceding trabeculectomy concurrent ocular diseases before or at the time of surgery history of intraocular or extraocular surgery that involved the conjunctiva previous laser surgery for glaucoma argon laser trabeculoplasty iridoplasty or peripheral iridotomy visual field mean deviation of the last field before surgery date of surgery type of conjunctival flap concentration and duration of mitomycin C application site and dose of subconjunctival Bevacizumab injection and intraoperative complications
Postoperative IOP number of medications visual acuity complications postoperative suture lysis and surgery performed after trabeculectomy will be recorded At each visit the examination will include measurement of Snellen best corrected visual acuity BCVA IOP using a calibrated applanation tonometer slit-lamp biomicroscopy Seidel testing and ophthalmoscopy Humphrey perimetry 24-2 or 10-2 will be done prior to surgery at 3 and 6 months post intervention to assess for objective disease progression There will be 7 post-operative and follow-up visits within 6 months of surgery postoperative days 1 7 14 30 60 90 and 180 A window of 7 days is allowed for the 30 60 90 day visits and 14 days for the 180 day visits On each visit Bleb photographs would be recorded and graded according to the Moorfields Bleb Grading Protocol by a single observer
Outcomes
Complete success will be defined as an IOP 18mmHg without anti- glaucoma medications at 6 months follow up after surgery or at least a 20 reduction from baseline IOP
Qualified Success will be defined as an IOP of 18mmHg with one anti-glaucoma medication
Failure will be defined as IOP 21 mmHg or not reduced by 20 below baseline on two consecutive follow-up visits after three months despite medication IOP 5 mmHg on two consecutive follow-up visits after three months additional glaucoma surgery or loss of light perception
Eyes that will be Seidel positive within the first month of follow-up will be classified as wound leaks and those occurring after one month will be categorized as bleb leaks Cataracts will be considered to have progressed if there is loss of 2 lines of Snellen BCVA that is attributed to the cataract at the six-month follow-up visit or after or if cataract surgery is performed
Statistical analysis Univariate comparisons between treatment groups will be made by the two-sided Student t test χ2 test or Fisher exact test The association of surgical complications with treatment outcome vision loss and cataract progression will be assessed for statistical significance with the χ2 test or Fisher exact test A p value of 05 or less will be considered statistically significant
Procedure Surgical technique Trabeculectomy will be performed after the administration of retrobulbar or peribulbar anesthesia with lidocaine For the limbus-based procedure a bridle suture 4-0 silk will be placed under the superior rectus muscle tendon and the conjunctiva and Tenons capsule will be incised in the superior quadrant 8 to 10 mm posterior to the surgical limbus The conjunctiva and Tenons capsule will be dissected anterior to the limbus Meticulous hemostasis will be achieved with bipolar cautery In cases randomized to MMC usage a cellulose sponge approximately 6 12 mm 1 mm soaked with mitomycin C 02 mgml will be applied over the intended site of the scleral flap for 1 to 3 minutes The duration of mitomycin C application will be based on the preoperative evaluation of each patients risk factors for failure Copious irrigation with balanced salt solution will be performed to wash away residual MMC A ½ to 23 thickness square scleral flap approximately 35 35 mm will be then dissected into the clear cornea After resection of an anterior trabecular block approximately 25 1 mm an iridectomy will be performed The scleral flap will be sutured with two or three 10-0 nylon sutures at its corners The conjunctiva and Tenons capsule will be closed in a single continuous layer with 8-0 Vicryl suture In the subjects randomized to receive Injection Bevacizumab 005 ml of reconstituted bevacizumab drug 125 mg will be injected subconjunctivally adjacent to the bleb Atropine eye ointment will be placed in the fornix and the eye will be patched In the early postoperative period all patients will be treated with topical corticosteroids four times daily for two weeks which will be tapered-off slowly over six to eight weeks Suture-lysis with argon laser will be performed under topical anesthesia when in the opinion of the surgeon filtration is judged to be too low and the IOP too high for the patient to meet the target pressure
Preparation of the Drug
Bevacizumab Avastin Avastin is available in a sterile vial 100 mg in 4 ml preservative free and in order to ensure safety the vial injection will be administered within one day
Subconjunctival Injections 125mg drug in 005ml will be given at the end of the surgery adjacent to the bleb raised using a single-use 30-gauge needle and a tuberculin syringe
Follow-Up The following demographic and clinical data will be extracted from the medical records of eligible patients race age of the patient at the time of surgery gender eye laterality preoperative visual acuity refractive error average of IOP readings during three months before surgery number of medications recorded during the three months preceding trabeculectomy concurrent ocular diseases before or at the time of surgery history of intraocular or extraocular surgery that involved the conjunctiva previous laser surgery for glaucoma argon laser trabeculoplasty iridoplasty or peripheral iridotomy visual field mean deviation of the last field before surgery date of surgery type of conjunctival flap concentration and duration of mitomycin C application site and dose of subconjunctival Bevacizumab injection and intraoperative complications
Postoperative IOP number of medications visual acuity complications postoperative suture lysis and surgery performed after trabeculectomy will be recorded At each visit the examination will include measurement of Snellen best corrected visual acuity BCVA IOP using a calibrated applanation tonometer slit-lamp biomicroscopy Seidel testing and ophthalmoscopy Humphrey perimetry 24-2 or 10-2 will be done prior to surgery at 3 and 6 months post intervention to assess for objective disease progression There will be 7 post-operative and follow-up visits within 6 months of surgery postoperative days 1 7 14 30 60 90 and 180 A window of 7 days is allowed for the 30 60 90 day visits and 14 days for the 180 day visits On each visit Bleb photographs would be recorded and graded according to the Moorfields Bleb Grading Protocol by a single observer
Outcomes
Complete success will be defined as an IOP 18mmHg without anti- glaucoma medications at 6 months follow up after surgery or at least a 20 reduction from baseline IOP
Qualified Success will be defined as an IOP of 18mmHg with one anti-glaucoma medication
Failure will be defined as IOP 21 mmHg or not reduced by 20 below baseline on two consecutive follow-up visits after three months despite medication IOP 5 mmHg on two consecutive follow-up visits after three months additional glaucoma surgery or loss of light perception
Eyes that will be Seidel positive within the first month of follow-up will be classified as wound leaks and those occurring after one month will be categorized as bleb leaks Cataracts will be considered to have progressed if there is loss of 2 lines of Snellen BCVA that is attributed to the cataract at the six-month follow-up visit or after or if cataract surgery is performed
Statistical analysis Univariate comparisons between treatment groups will be made by the two-sided Student t test χ2 test or Fisher exact test The association of surgical complications with treatment outcome vision loss and cataract progression will be assessed for statistical significance with the χ2 test or Fisher exact test A p value of 05 or less will be considered statistically significant
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None