<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/NCT02258009</url>
  </required_header>
  <id_info>
    <org_study_id>CRFB002DDE25</org_study_id>
    <nct_id>NCT02258009</nct_id>
  </id_info>
  <brief_title>Systemic VEGF Protein Dynamics Following Intravitreal Injections of Ranibizumab Versus Aflibercept in Patients With Visual Impairment Due to Diabetic Macular Edema</brief_title>
  <acronym>TIDE DME</acronym>
  <official_title>A Randomized, Single-blinded, Multicenter, Phase IV Study to Compare Systemic VEGF Protein Dynamics Following Monthly Intravitreal Injections of 0.5 mg Ranibizumab Versus 2 mg Aflibercept Until Study Week 12 in Patients With Visual Impairment Due to Diabetic Macular Edema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to compare the effect of intravitreal injections of ranibizumab&#xD;
      and aflibercept on systemic VEGF protein levels in DME patients in a detailed time course.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <start_date>October 2015</start_date>
  <completion_date type="Anticipated">October 2016</completion_date>
  <primary_completion_date type="Anticipated">October 2016</primary_completion_date>
  <phase>Phase 4</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>Systemic VEGF-A protein levels</measure>
    <time_frame>From baseline to study week 12</time_frame>
    <description>Systemic VEGF-A protein levels following monthly intravitreal injections of 0.5 mg ranibizumab versus 2 mg aflibercept (Area under the curve)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Systemic VEGF-A protein levels</measure>
    <time_frame>From study week 12 to 24</time_frame>
    <description>Systemic VEGF-A protein levels in patients switching from monthly 2 mg aflibercept injections to monthly 0.5 mg ranibizumab compared to patients treated with 0.5 mg ranibizumab from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Systemic VEGF-A levels</measure>
    <time_frame>From study week 12 to 24</time_frame>
    <description>Adjustment of systemic VEGF-A levels of patients switching from aflibercept to ranibizumab to levels comparable to baseline or to levels comparable as in patients treated from baseline with ranibizumab</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Visual Impairment Due to Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Monthly intravitreal injections of 0.5 mg ranibizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Three monthly intravitreal injections of 2 mg aflibercept followed by three monthly intravitreal injections of 0.5 mg ranibizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ranibizumab</intervention_name>
    <description>0.5 mg intravitreal injections</description>
    <arm_group_label>Group 1</arm_group_label>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Lucentis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>2 mg intravitreal injections</description>
    <arm_group_label>Group 2</arm_group_label>
    <other_name>Eylea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 or Type 2 diabetes mellitus&#xD;
&#xD;
          -  Visual impairment predominantly due to DME.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Stroke or myocardial infarction less than 3 months prior to screening.&#xD;
&#xD;
          -  Presence of uncontrolled systolic blood pressure or diastolic blood pressure&#xD;
&#xD;
          -  Renal failure requiring dialysis or renal transplant or renal insufficiency&#xD;
&#xD;
          -  Untreated diabetes mellitus&#xD;
&#xD;
          -  Use of any systemic anti-VEGF drugs&#xD;
&#xD;
          -  Use of systemic or inhaled corticosteroids for at least 30 consecutive days within 3&#xD;
             months prior to screening.&#xD;
&#xD;
          -  Women who are pregnant or breast feeding or who are menstruating and capable of&#xD;
             becoming pregnant* and not practicing a medically approved method of contraception&#xD;
&#xD;
        For either eye:&#xD;
&#xD;
          -  Any active periocular or ocular infection or inflammation&#xD;
&#xD;
          -  Uncontrolled glaucoma&#xD;
&#xD;
          -  Neovascularization of the iris or neovascular glaucoma&#xD;
&#xD;
          -  History of treatment with any anti-angiogenic drugs&#xD;
&#xD;
        For study eye:&#xD;
&#xD;
          -  Atrophy or fibrosis involving the center of the fovea at the time of screening or&#xD;
             baseline.&#xD;
&#xD;
          -  Cataract (if causing significant visual impairment), planned cataract surgery during&#xD;
             the study period, vitrectomy, aphakia, glaucoma surgery, severe vitreous hemorrhage,&#xD;
             rhegmatogenous retinal detachment, proliferative retinopathy or choroidal&#xD;
             neovascularization or macular edema of any other cause than DME&#xD;
&#xD;
          -  Irreversible structural damage within 0.5 disc diameter of the center of the macula&#xD;
&#xD;
          -  Panretinal laser photocoagulation within 6 months prior to randomization.&#xD;
&#xD;
          -  Focal/grid laser photocoagulation within 3 months prior to randomization.&#xD;
&#xD;
          -  Any intraocular procedure (including cataract surgery, Yttrium-Aluminum-Garnet&#xD;
             capsulotomy) within 3 months prior to baseline or anticipated within the next 6 months&#xD;
             following&#xD;
&#xD;
          -  Topical ocular corticosteroids administered for at least 30 consecutive days within 3&#xD;
             months prior to screening.&#xD;
&#xD;
          -  Application of intravitreal corticosteroids in vitreous within 6 months prior to&#xD;
             screening. Prior application of fluocinolonacetonid releasing implant in vitreous&#xD;
             within 36 months prior to screening.&#xD;
&#xD;
        For fellow eye&#xD;
&#xD;
        - Retinal or choroidal neovascularization or macula edema of any cause&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceutical</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chemnitz</city>
        <zip>09113</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 7, 2014</study_first_posted>
  <last_update_submitted>October 26, 2016</last_update_submitted>
  <last_update_submitted_qc>October 26, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 27, 2016</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>Vision Disorders</mesh_term>
    <mesh_term>Vision, Low</mesh_term>
    <mesh_term>Macular Edema</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ranibizumab</mesh_term>
    <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/NCT02258009
org study id: CRFB002DDE25
nct id: NCT02258009
lead sponsor: 
has dmc: No
The purpose of the study is to compare the effect of intravitreal injections of ranibizumab
      and aflibercept on systemic VEGF protein levels in DME patients in a detailed time course.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Systemic VEGF-A protein levels
time frame: From baseline to study week 12
description: Systemic VEGF-A protein levels following monthly intravitreal injections of 0.5 mg ranibizumab versus 2 mg aflibercept (Area under the curve)
measure: Systemic VEGF-A protein levels
time frame: From study week 12 to 24
description: Systemic VEGF-A protein levels in patients switching from monthly 2 mg aflibercept injections to monthly 0.5 mg ranibizumab compared to patients treated with 0.5 mg ranibizumab from baseline
measure: Systemic VEGF-A levels
time frame: From study week 12 to 24
description: Adjustment of systemic VEGF-A levels of patients switching from aflibercept to ranibizumab to levels comparable to baseline or to levels comparable as in patients treated from baseline with ranibizumab
arm group label: Group 1
arm group type: Experimental
description: Monthly intravitreal injections of 0.5 mg ranibizumab
arm group label: Group 2
arm group type: Experimental
description: Three monthly intravitreal injections of 2 mg aflibercept followed by three monthly intravitreal injections of 0.5 mg ranibizumab
intervention type: Drug
intervention name: Ranibizumab
description: 0.5 mg intravitreal injections
arm group label: Group 1
arm group label: Group 2
other name: Lucentis
intervention type: Drug
intervention name: Aflibercept
description: 2 mg intravitreal injections
arm group label: Group 2
other name: Eylea
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceutical
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
country: Germany
responsible party type: Sponsor
mesh term: Vision Disorders
mesh term: Vision, Low
mesh term: Macular Edema
mesh term: Edema
mesh term: Ranibizumab
mesh term: Aflibercept