<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/NCT03804099</url>
  </required_header>
  <id_info>
    <org_study_id>01-05.01</org_study_id>
    <nct_id>NCT03804099</nct_id>
  </id_info>
  <brief_title>Effect Aflibercept on Ocular Perfusion</brief_title>
  <official_title>The Effect of Intravitreal Aflibercept on Ocular Perfusion - a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Augenabteilung Allgemeines Krankenhaus Linz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Augenabteilung Allgemeines Krankenhaus Linz</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>
      Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment&#xD;
      in Western Countries. It is a well-established fact that vascular endothelial growth factor&#xD;
      (VEGF) plays a key part in the development of the neovascular (or exsudative) form of AMD.&#xD;
      Today, VEGF-inhibition by means of injection of anti-VEGF agents into the vitreous cavity&#xD;
      constitutes the gold standard of AMD therapy. In physiological conditions, VEGF acts as a&#xD;
      vasodilator by activating endothelial nitric oxide synthase. As a consequence, VEGF&#xD;
      inhibition should result in significant ocular vasoconstriction, which has in fact been&#xD;
      demonstrated for bevacizumab and ranibizumab, two of the three available VEGF-inhibitors. The&#xD;
      understanding and awareness of potentially harmful implications of the induced&#xD;
      vasoconstriction on retinal and/or optic nerve head structure and function is sparse. This is&#xD;
      especially delicate, as most patients with exsudative AMD require repeated injections on a&#xD;
      monthly basis for many years. Aflibercept, the latest anti-VEGF agent approved for&#xD;
      intravitreal use in 2011, offers a superior binding affinity for VEGF compared to the former&#xD;
      two drugs. However, as of today, its effect on ocular circulation is unclear. With Laser&#xD;
      Speckle Flowgraphy (LSFG), a commercially available, non-invasive and patient-friendly method&#xD;
      for the evaluation of blood flow at the optic nerve head, the choroid and retina has arisen&#xD;
      in recent years.&#xD;
&#xD;
      We aim to measure ocular perfusion with LSFG before and after 3 consecutive injections of&#xD;
      aflibercept in unilateral neovascular age-related maculopathy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">May 18, 2018</completion_date>
  <primary_completion_date type="Actual">March 20, 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean blur ratio (LSFG)</measure>
    <time_frame>Baseline, 1 week (at the time point of injection 2 and 3), 1 month after injection 3</time_frame>
    <description>Quantitative parameter of red blood cells velocity</description>
  </primary_outcome>
  <enrollment type="Actual">20</enrollment>
  <condition>Macular Degeneration</condition>
  <condition>Anti Vascular Endothelial Growth Factor</condition>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept Injection [Eylea]</intervention_name>
    <description>After instillation of topical anesthetic, sterilization of the eyelid, and instillation of 1.25% povidone-iodine drops, 2.0 mg/0.05 mL of aflibercept (Eylea) is injected into the vitreous cavity through a standard pars plana approach (3.5 mm posterior to the limbus) under sterile conditions</description>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women aged over 50 years&#xD;
&#xD;
          -  written informed consent for participation in the study&#xD;
&#xD;
          -  Scheduled for 3 consecutive intravitreal injections (4 week intervals) of aflibercept&#xD;
             for treatment of exudative AMD in one eye&#xD;
&#xD;
          -  Subject is generally healthy with no current significant or a history of a significant&#xD;
             neurological, cardiovascular, pulmonary (including asthma), hepatic, metabolic,&#xD;
             rheumatic, autoimmune, hematological or renal disorder, as determined by the&#xD;
             investigator's clinical judgment through collection of medical history and performance&#xD;
             of a physical examination. A significant disorder is defined as a disease or medical&#xD;
             condition associated with impaired health status, requiring regular or current medical&#xD;
             treatment and/or follow up. For the purposes of this study, an investigator may&#xD;
             classify a medical condition as a nonsignificant disorder despite the fact that the&#xD;
             subject receives treatment. Subjects having controlled Stage 1 hypertension (blood&#xD;
             pressure of 140-159 mmHg systolic and/or 90-99 mmHg diastolic) are eligible for&#xD;
             participation in this study.&#xD;
&#xD;
          -  Normal findings in the medical history unless the investigator considers an&#xD;
             abnormality to be clinically irrelevant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active exudative AMD requiring treatment of both eyes&#xD;
&#xD;
          -  Ocular surgery (including intravitreal injection) during the 3 months preceding the&#xD;
             study&#xD;
&#xD;
          -  Vitrectomized eyes&#xD;
&#xD;
          -  Ametropia &gt; 6 Dpt&#xD;
&#xD;
          -  Relevant ophthalmic diseases/conditions that could interfere with LSFG measurements&#xD;
             (e.g. glaucoma, optic nerve head drusen, tilted disc, etc.)&#xD;
&#xD;
          -  Ocular infection or clinically significant inflammation&#xD;
&#xD;
          -  Opacities of the cornea (e.g. corneal scars, corneal oedema), the lens (e.g. LOCS-II&#xD;
             grading &gt; 2, posterior capsule opacification) or the vitreous (e.g. vitreous&#xD;
             haemorrhage, asteroid hyalosis)&#xD;
&#xD;
          -  Patients who are not able to cooperate or with insufficient ability to fixate (tremor,&#xD;
             nystagmus)&#xD;
&#xD;
          -  Blood donation in the 3 weeks preceding the study&#xD;
&#xD;
          -  Participation in a clinical trial in the 3 weeks preceding the study&#xD;
&#xD;
          -  Pre- or perimenopausal women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Ophthalmology, Kepler University Hospital</name>
      <address>
        <city>Linz</city>
        <zip>4020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>June 29, 2018</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>January 14, 2019</last_update_submitted>
  <last_update_submitted_qc>January 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Macular Degeneration</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03804099
org study id: 01-05.01
nct id: NCT03804099
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment
      in Western Countries. It is a well-established fact that vascular endothelial growth factor
      (VEGF) plays a key part in the development of the neovascular (or exsudative) form of AMD.
      Today, VEGF-inhibition by means of injection of anti-VEGF agents into the vitreous cavity
      constitutes the gold standard of AMD therapy. In physiological conditions, VEGF acts as a
      vasodilator by activating endothelial nitric oxide synthase. As a consequence, VEGF
      inhibition should result in significant ocular vasoconstriction, which has in fact been
      demonstrated for bevacizumab and ranibizumab, two of the three available VEGF-inhibitors. The
      understanding and awareness of potentially harmful implications of the induced
      vasoconstriction on retinal and/or optic nerve head structure and function is sparse. This is
      especially delicate, as most patients with exsudative AMD require repeated injections on a
      monthly basis for many years. Aflibercept, the latest anti-VEGF agent approved for
      intravitreal use in 2011, offers a superior binding affinity for VEGF compared to the former
      two drugs. However, as of today, its effect on ocular circulation is unclear. With Laser
      Speckle Flowgraphy (LSFG), a commercially available, non-invasive and patient-friendly method
      for the evaluation of blood flow at the optic nerve head, the choroid and retina has arisen
      in recent years.

      We aim to measure ocular perfusion with LSFG before and after 3 consecutive injections of
      aflibercept in unilateral neovascular age-related maculopathy.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean blur ratio (LSFG)
time frame: Baseline, 1 week (at the time point of injection 2 and 3), 1 month after injection 3
description: Quantitative parameter of red blood cells velocity
intervention type: Drug
intervention name: Aflibercept Injection [Eylea]
description: After instillation of topical anesthetic, sterilization of the eyelid, and instillation of 1.25% povidone-iodine drops, 2.0 mg/0.05 mL of aflibercept (Eylea) is injected into the vitreous cavity through a standard pars plana approach (3.5 mm posterior to the limbus) under sterile conditions
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: Austria
responsible party type: Sponsor
mesh term: Macular Degeneration
mesh term: Aflibercept