<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03766425</url>
  </required_header>
  <id_info>
    <org_study_id>KE-0254/133/2017</org_study_id>
    <nct_id>NCT03766425</nct_id>
  </id_info>
  <brief_title>Comparison of Efficacy and Safety of Mitomycin and Aflibercept Used to Support Primary Trabeculectomy.</brief_title>
  <official_title>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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Lublin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Lublin</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Comparison of efficacy and safety of Mitomycin and Aflibercept used to support primary&#xD;
      trabeculectomy - a prospective, randomized trial in patients with open-angle glaucoma&#xD;
      undergoing surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Glaucoma is a neurodegenerative disease characterized by progressive dying of retinal&#xD;
      ganglion cells, axonal loss and damage to the optic nerve. This leads to a gradual loss of&#xD;
      the visual field, and in the final stage to blindness. High intraocular pressure is&#xD;
      considered to be the main risk factor for glaucomatous neuropathy. In the treatment we use&#xD;
      pharmacological therapies and surgical treatment. The trabeculectomy has been the golden&#xD;
      standard for the treatment of glaucoma for many years. This procedure consisting in the&#xD;
      creation of a filtering bleb, which allows drainage of aqueous humor from within the eye to&#xD;
      underneath the conjunctiva where it is absorbed. in addition to the surgery,&#xD;
      anti-proliferative substances play a significant role in suppressing the physiological&#xD;
      healing process. Bleb insufficiency observed in the postoperative period results to a large&#xD;
      extent from progressive scarring of the follicle, which is responsible for excessive&#xD;
      fibroblast proliferation and subconjunctival fibrosis.&#xD;
&#xD;
      Mitomycin is an antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of&#xD;
      the bi- or tri-functional alkylating agents causing cross-linking of DNA and inhibition of&#xD;
      DNA synthesis. Its properties cause that mitomycin is now a popular medicine used to support&#xD;
      trabeculectomy, with proven effectiveness of inhibiting the unwanted healing process of the&#xD;
      fistula, and thus extend its period of its proper functioning.&#xD;
&#xD;
      Aflibercept is an inhibitor of vascular endothelial growth factor (VEGF). Its properties&#xD;
      cause inhibition of the pathological process of formation of new vessels and their excessive&#xD;
      permeability, as well as reduction of leukocyte infiltration and inflammation.&#xD;
&#xD;
      The aim of the research:&#xD;
&#xD;
      Comparison of the effectiveness of primary trabeculectomy in patients with open angle&#xD;
      glaucoma supported with Eylea (Aflibercept) compared to the group of patients treated with&#xD;
      mitomycin.&#xD;
&#xD;
      Materials and methods:&#xD;
&#xD;
      The research conducted at the Department of Glaucoma Diagnostics and Microsurgery in Medical&#xD;
      University of Lublin will include patients treated with antiproliferative substances and&#xD;
      trabeculectomy. Two groups of patients will participate in the study:&#xD;
&#xD;
      Group I - patients qualified for mitomycin trabeculectomy Group II - patients qualified for&#xD;
      Eylea assisted trabeculectomy (Aflibercept) Mitomycin will be administered in the first group&#xD;
      of patients during an operation at a dose of 0.3mg / ml for 3 minutes on a soaked sponge.&#xD;
      Aflibercept will be applied intraoperatively in a dose of of 0.05 ml (40 mg / ml)&#xD;
      subconjunctival and one week after surgery in the same dose.&#xD;
&#xD;
      Criteria for inclusion:&#xD;
&#xD;
        1. Open angle glaucoma or capsular glaucoma.&#xD;
&#xD;
        2. Patient's age&gt; 40 years&#xD;
&#xD;
        3. Local treatment ineffective due to:&#xD;
&#xD;
             1. intraocular pressure more than 21mmHg with maximum pharmacological therapy (using&#xD;
                B-blocker + carbonic anhydrase + prostaglandins) or&#xD;
&#xD;
             2. intolerance to topical treatment or&#xD;
&#xD;
             3. progression in the visual field examination (assessed on the basis of MD, PSD).&#xD;
&#xD;
        4. Lack of previous ophthalmological surgical interventions.&#xD;
&#xD;
        5. No previous laser gonioplasty.&#xD;
&#xD;
        6. No previous laser trabeculoplasty or laser trabeculoplasty performed for more than a&#xD;
           year.&#xD;
&#xD;
      Exclusion criteria:&#xD;
&#xD;
        1. Patient with angle-closure glaucoma or secondary glaucoma (except for glaucoma in the&#xD;
           course of pseudoexfoliation syndrome).&#xD;
&#xD;
        2. One-eye patient.&#xD;
&#xD;
        3. A patient with pseudophakia or aphakia.&#xD;
&#xD;
        4. Patient after previous ophthalmic procedures (phacoemulsification with intraocular lens&#xD;
           implantation, traditional pars plana vitrectomy, keratoplasty).&#xD;
&#xD;
        5. A patient diagnosed or suspected of having uveitis or intraocular inflammation.&#xD;
&#xD;
        6. Any corneal abnormalities or other conditions that make it impossible to reliably test&#xD;
           with an applanation tonometer in the treated eye, including earlier refractive surgery&#xD;
           of the eye&#xD;
&#xD;
      The efficacy of surgery in both groups will be assessed at subsequent postoperative controls&#xD;
      based on the following diagnostic tests:&#xD;
&#xD;
        -  Visual acuity examination;&#xD;
&#xD;
        -  Intraocular pressure examination;&#xD;
&#xD;
        -  Evaluation of the filtering bleb in the slit lamp;&#xD;
&#xD;
        -  A photo of the filtering bleb;&#xD;
&#xD;
        -  Optical coherence tomography of the filtration bleb;&#xD;
&#xD;
        -  Visual field;&#xD;
&#xD;
        -  Study of corneal endothelial cell density.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">June 14, 2017</start_date>
  <completion_date type="Anticipated">July 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">July 31, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Effectiveness of aflibercept and mitomycin on the morphology of the bleb;</measure>
    <time_frame>1 year</time_frame>
    <description>Rating the bleb in The Indiana Bleb Appearance Grading Scale, describing bleb height, extent, vascularity, and leakage with the Seidel test.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effectiveness of aflibercept and mitomycin on the function of the bleb;</measure>
    <time_frame>1 year</time_frame>
    <description>Measurement of intraocular pressure (Goldmann applanation tonometer) and taking a photo of a bleb.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Impact of tested substances on visual acuity after surgery</measure>
    <time_frame>1 year</time_frame>
    <description>Examination of a visual acuity 1 week after operation as well as 1 month, 3 months, 6 months, 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The influence of aflibercept and mitomycin on corneal endothelial cell density after surgery</measure>
    <time_frame>1 year</time_frame>
    <description>Examination of the corneal endothelial cell density before the surgery as well as 6 months and 12 months after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of used substances on visual field parameters</measure>
    <time_frame>1 year</time_frame>
    <description>Examination of a visual field in SITA (Swedish Interactive Testing Algorithm) FAST strategy before the surgery and 12 months after surgery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequencies and type of possible complications.</measure>
    <time_frame>1 year</time_frame>
    <description>observing and recording all complications and side effects in both groups of patients</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">64</enrollment>
  <condition>Eye Diseases</condition>
  <condition>Optic Nerve Damage</condition>
  <condition>Glaucoma Surgery</condition>
  <arm_group>
    <arm_group_label>Aflibercept</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mitomycin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Mitomycin applied during a surgery at a concentration of 0.3mg / ml for 3 min. on a soaked sponge.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>subconjunctival injection</description>
    <arm_group_label>Aflibercept</arm_group_label>
    <other_name>Eylea, Zaltrap</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mitomycin</intervention_name>
    <description>subconjunctival injection</description>
    <arm_group_label>Mitomycin</arm_group_label>
    <other_name>Ametycine, Mit-C, Mitomycin C</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Primary open-angle glaucoma or capsular glaucoma.&#xD;
&#xD;
          2. Patient's age: over 40 years, no sex preference;&#xD;
&#xD;
          3. Local treatment ineffective due to:&#xD;
&#xD;
               1. Intraocular pressure above 21mmHg at maximum pharmacological therapy (using&#xD;
                  β-blocker + carbonic anhydrase inhibitor + prostaglandins) or&#xD;
&#xD;
               2. Intolerance to topical treatment or&#xD;
&#xD;
               3. Progression in visual field examination&#xD;
&#xD;
          4. Lack of previous ophthalmological surgical interventions.&#xD;
&#xD;
          5. Lack of previously performed laser gonioplasty.&#xD;
&#xD;
          6. No laser trabeculoplasty or laser trabeculoplasty performed for more than a year.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient with primary closed-angle glaucoma or secondary glaucoma (except for glaucoma&#xD;
             in the course of pseudoexfoliation syndrome).&#xD;
&#xD;
          2. One-eye patient.&#xD;
&#xD;
          3. Patient with aphakia.&#xD;
&#xD;
          4. Patient after previous ophthalmic procedures (cataract removal by phacoemulsification&#xD;
             with an implant of an intraocular lens, vitrectomy by pars plana, keratoplasty).&#xD;
&#xD;
          5. A patient diagnosed or suspected of having uveitis or intraocular inflammation.&#xD;
&#xD;
          6. Any corneal abnormalities or other conditions that prevent reliable testing with an&#xD;
             applanation device in the treated eye, including earlier refractive surgery of the&#xD;
             eye.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Medical University of Lublin</name>
      <address>
        <city>Lublin</city>
        <state>Lubelskie</state>
        <zip>20-059</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
  </location_countries>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>December 4, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>December 4, 2018</last_update_submitted>
  <last_update_submitted_qc>December 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Lublin</investigator_affiliation>
    <investigator_full_name>Justyna Kaproń-Świś</investigator_full_name>
    <investigator_title>Medical Doctor</investigator_title>
  </responsible_party>
  <keyword>aflibercept</keyword>
  <keyword>glaucoma</keyword>
  <keyword>mitomycin</keyword>
  <keyword>trabeculectomy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glaucoma</mesh_term>
    <mesh_term>Eye Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
    <mesh_term>Mitomycins</mesh_term>
    <mesh_term>Mitomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03766425
org study id: KE-0254/133/2017
nct id: NCT03766425
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Effectiveness of aflibercept and mitomycin on the morphology of the bleb;
time frame: 1 year
description: Rating the bleb in The Indiana Bleb Appearance Grading Scale, describing bleb height, extent, vascularity, and leakage with the Seidel test.
measure: Effectiveness of aflibercept and mitomycin on the function of the bleb;
time frame: 1 year
description: Measurement of intraocular pressure (Goldmann applanation tonometer) and taking a photo of a bleb.
measure: Impact of tested substances on visual acuity after surgery
time frame: 1 year
description: Examination of a visual acuity 1 week after operation as well as 1 month, 3 months, 6 months, 12 months
measure: The influence of aflibercept and mitomycin on corneal endothelial cell density after surgery
time frame: 1 year
description: Examination of the corneal endothelial cell density before the surgery as well as 6 months and 12 months after surgery
measure: Impact of used substances on visual field parameters
time frame: 1 year
description: Examination of a visual field in SITA (Swedish Interactive Testing Algorithm) FAST strategy before the surgery and 12 months after surgery
measure: Frequencies and type of possible complications.
time frame: 1 year
description: observing and recording all complications and side effects in both groups of patients
arm group label: Aflibercept
arm group type: Experimental
description: 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.
arm group label: Mitomycin
arm group type: Active Comparator
description: Mitomycin applied during a surgery at a concentration of 0.3mg / ml for 3 min. on a soaked sponge.
intervention type: Drug
intervention name: Aflibercept
description: subconjunctival injection
arm group label: Aflibercept
other name: Eylea, Zaltrap
intervention type: Drug
intervention name: Mitomycin
description: subconjunctival injection
arm group label: Mitomycin
other name: Ametycine, Mit-C, Mitomycin C
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Poland
responsible party type: Principal Investigator
investigator affiliation: Medical University of Lublin
investigator full name: Justyna Kaproń-Świś
investigator title: Medical Doctor
mesh term: Glaucoma
mesh term: Eye Diseases
mesh term: Aflibercept
mesh term: Mitomycins
mesh term: Mitomycin
sharing ipd: Undecided