Comparison of Efficacy and Safety of Mitomycin and Aflibercept Used to Support Primary Trabeculectomy.

Comparison of Efficacy and Safety of Mitomycin and Aflibercept Used to Support Primary Trabeculectomy - a Prospective, Randomized Trial in Patients With Open-angle Glaucoma Undergoing Surgery.

Comparison of efficacy and safety of Mitomycin and Aflibercept used to support primary trabeculectomy - a prospective, randomized trial in patients with open-angle glaucoma undergoing surgery.

Study Overview

• Status: Completed
• Conditions: Eye Diseases; Glaucoma Surgery; Optic Nerve Damage
• Intervention / Treatment: Drug: Aflibercept; Drug: Mitomycin

Detailed Description

Glaucoma is a neurodegenerative disease characterized by progressive dying of retinal ganglion cells, axonal loss and damage to the optic nerve. This leads to a gradual loss of the visual field, and in the final stage to blindness. High intraocular pressure is considered to be the main risk factor for glaucomatous neuropathy. In the treatment we use pharmacological therapies and surgical treatment. The trabeculectomy has been the golden standard for the treatment of glaucoma for many years. This procedure consisting in the creation of a filtering bleb, which allows drainage of aqueous humor from within the eye to underneath the conjunctiva where it is absorbed. in addition to the surgery, anti-proliferative substances play a significant role in suppressing the physiological healing process. Bleb insufficiency observed in the postoperative period results to a large extent from progressive scarring of the follicle, which is responsible for excessive fibroblast proliferation and subconjunctival fibrosis.

Mitomycin is an antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional alkylating agents causing cross-linking of DNA and inhibition of DNA synthesis. Its properties cause that mitomycin is now a popular medicine used to support trabeculectomy, with proven effectiveness of inhibiting the unwanted healing process of the fistula, and thus extend its period of its proper functioning.

Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF). Its properties cause inhibition of the pathological process of formation of new vessels and their excessive permeability, as well as reduction of leukocyte infiltration and inflammation.

The aim of the research:

Comparison of the effectiveness of primary trabeculectomy in patients with open angle glaucoma supported with Eylea (Aflibercept) compared to the group of patients treated with mitomycin.

Materials and methods:

The research conducted at the Department of Glaucoma Diagnostics and Microsurgery in Medical University of Lublin will include patients treated with antiproliferative substances and trabeculectomy. Two groups of patients will participate in the study:

Group I - patients qualified for mitomycin trabeculectomy Group II - patients qualified for Eylea assisted trabeculectomy (Aflibercept) Mitomycin will be administered in the first group of patients during an operation at a dose of 0.3mg / ml for 3 minutes on a soaked sponge. Aflibercept will be applied intraoperatively in a dose of of 0.05 ml (40 mg / ml) subconjunctival and one week after surgery in the same dose.

Criteria for inclusion:

1. Open angle glaucoma or capsular glaucoma.
2. Patient's age> 40 years

3. Local treatment ineffective due to:

   1. intraocular pressure more than 21mmHg with maximum pharmacological therapy (using B-blocker + carbonic anhydrase + prostaglandins) or
   2. intolerance to topical treatment or
   3. progression in the visual field examination (assessed on the basis of MD, PSD).
4. Lack of previous ophthalmological surgical interventions.
5. No previous laser gonioplasty.
6. No previous laser trabeculoplasty or laser trabeculoplasty performed for more than a year.

Exclusion criteria:

1. Patient with angle-closure glaucoma or secondary glaucoma (except for glaucoma in the course of pseudoexfoliation syndrome).
2. One-eye patient.
3. A patient with pseudophakia or aphakia.
4. Patient after previous ophthalmic procedures (phacoemulsification with intraocular lens implantation, traditional pars plana vitrectomy, keratoplasty).
5. A patient diagnosed or suspected of having uveitis or intraocular inflammation.
6. Any corneal abnormalities or other conditions that make it impossible to reliably test with an applanation tonometer in the treated eye, including earlier refractive surgery of the eye

The efficacy of surgery in both groups will be assessed at subsequent postoperative controls based on the following diagnostic tests:

• Visual acuity examination;
• Intraocular pressure examination;
• Evaluation of the filtering bleb in the slit lamp;
• A photo of the filtering bleb;
• Optical coherence tomography of the filtration bleb;
• Visual field;
• Study of corneal endothelial cell density.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Poland
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-059
      • Medical University of Lublin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Primary open-angle glaucoma or capsular glaucoma.
2. Patient's age: over 40 years, no sex preference;

3. Local treatment ineffective due to:

   1. Intraocular pressure above 21mmHg at maximum pharmacological therapy (using β-blocker + carbonic anhydrase inhibitor + prostaglandins) or
   2. Intolerance to topical treatment or
   3. Progression in visual field examination
4. Lack of previous ophthalmological surgical interventions.
5. Lack of previously performed laser gonioplasty.
6. No laser trabeculoplasty or laser trabeculoplasty performed for more than a year.

Exclusion Criteria:

1. Patient with primary closed-angle glaucoma or secondary glaucoma (except for glaucoma in the course of pseudoexfoliation syndrome).
2. One-eye patient.
3. Patient with aphakia.
4. Patient after previous ophthalmic procedures (cataract removal by phacoemulsification with an implant of an intraocular lens, vitrectomy by pars plana, keratoplasty).
5. A patient diagnosed or suspected of having uveitis or intraocular inflammation.
6. Any corneal abnormalities or other conditions that prevent reliable testing with an applanation device in the treated eye, including earlier refractive surgery of the eye.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept; Aflibercept applied intraoperatively as a subconjunctival injection at a dose of 0.05 ml (40 mg / ml) and one week after the operation at the same dose, also subconjunctival.	Drug: Aflibercept; subconjunctival injection; Other Names: Eylea, Zaltrap
Active Comparator: Mitomycin; Mitomycin applied during a surgery at a concentration of 0.3mg / ml for 3 min. on a soaked sponge.	Drug: Mitomycin; subconjunctival injection; Other Names: Ametycine, Mit-C, Mitomycin C

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness of aflibercept and mitomycin on the morphology of the bleb;	Rating the bleb in The Indiana Bleb Appearance Grading Scale, describing bleb height, extent, vascularity, and leakage with the Seidel test.	1 year
Effectiveness of aflibercept and mitomycin on the function of the bleb;	Measurement of intraocular pressure (Goldmann applanation tonometer) and taking a photo of a bleb.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of tested substances on visual acuity after surgery	Examination of a visual acuity 1 week after operation as well as 1 month, 3 months, 6 months, 12 months	1 year
The influence of aflibercept and mitomycin on corneal endothelial cell density after surgery	Examination of the corneal endothelial cell density before the surgery as well as 6 months and 12 months after surgery	1 year
Impact of used substances on visual field parameters	Examination of a visual field in SITA (Swedish Interactive Testing Algorithm) FAST strategy before the surgery and 12 months after surgery	1 year
Frequencies and type of possible complications.	observing and recording all complications and side effects in both groups of patients	1 year

Collaborators and Investigators

• Sponsor: Medical University of Lublin
• Investigators: Study Director: Tomasz Żarnowski, PhD, Medical Uniwersity of Lublin al. Racławickie 1 20-059 Lublin; Principal Investigator: Justyna Kaproń-Swiś, MD, Medical Uniwersity of Lublin al. Racławickie 1 20-059 Lublin

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2017
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: December 4, 2018
• First Posted (Actual): December 6, 2018

Study Record Updates

• Last Update Posted (Actual): October 27, 2023
• Last Update Submitted That Met QC Criteria: October 26, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: glaucoma; aflibercept; trabeculectomy; mitomycin
• Additional Relevant MeSH Terms: Ocular Hypertension; Glaucoma; Eye Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Alkylating Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antibiotics, Antineoplastic; Mitomycins; Mitomycin; Aflibercept
• Other Study ID Numbers: KE-0254/133/2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No