<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/NCT03751501</url>
  </required_header>
  <id_info>
    <org_study_id>P18-01</org_study_id>
    <nct_id>NCT03751501</nct_id>
  </id_info>
  <brief_title>Targeted Laser in Diabetic Macular Edema</brief_title>
  <acronym>TaLa-DME</acronym>
  <official_title>Photocoagulation of Capillary Macro-aneurysms in Addition to the Standard Treatment of Macular Edema Due to Diabetic Retinopathy. &quot;TaLa_DME&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Our hypothesis is that implementing laser photocoagulation (IGTL) as an adjunctive treatment&#xD;
      to intravitreal injections should lead to a significant reduction in the need for&#xD;
      intravitreal injections in patients with diabetic macular edema without adverse consequences&#xD;
      for visual acuity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be French, multicenter parallel group, 2-arms, randomized, sham&#xD;
      laser-controlled, double-blind trial evaluating the effect of IGTL as an adjunctive procedure&#xD;
      to intravitreal injections in patients with DME.&#xD;
&#xD;
      Acts which are the subject of the study: indocyanine green-Guided Targeted Laser&#xD;
      photocoagulation (IGTL): this combines routine procedures, that are, the detection of&#xD;
      macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser&#xD;
      verification of the effectiveness of the photothrombosis by OCT.&#xD;
&#xD;
      Study act: the treatment study includes a baseline laser treatment (experimental group) or&#xD;
      sham laser (control group) at randomization, repeated if needed 3 month later, administered&#xD;
      in combination with anti VEGF treatment, consisting of 3 monthly injections in the first 3&#xD;
      months, and a maintenance phase with monthly visits where retreatment is administered as&#xD;
      needed through a PRN regimen, based on morphological (retinal thickness on OCT) and&#xD;
      functional (visual acuity) criteria.&#xD;
&#xD;
      To evaluate the interest of IGTL in real conditions, the choice of the anti VEGF treatment&#xD;
      used for intravitreal injection (Ranibizumab or Aflibercept, which have French marketing&#xD;
      authorizations) is left to each investigator (equivalent therapeutic efficacy). Bevacizumab&#xD;
      is ruled out due to its lower efficacy compared with Aflibercept among eyes with worse&#xD;
      baseline VA, that represent the majority of the patients in our study. In addition,&#xD;
      bevacizumab is currently off-label in France for DME If both eyes are eligible at the time of&#xD;
      randomization, only one eye will be included and analyzed. However, the fellow eye will be&#xD;
      treated with the randomization-assigned treatment and the testing will be performed on each&#xD;
      eye.&#xD;
&#xD;
      Risks and constraints involved in the study: these procedures are commonly done in&#xD;
      ophthalmology care settings; no additional risk is expected due to the study.&#xD;
&#xD;
      Expected benefits for the participants and for the company: These procedures are commonly&#xD;
      done in ophthalmology care settings; no additional risk is expected due to the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">November 22, 2018</start_date>
  <completion_date type="Anticipated">October 24, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 24, 2019</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Eligible participants will be randomized into one of the 2 study arms groups: &quot;standard of care&quot; group with sham laser or experimental group with laser.&#xD;
Both group with laser or sham laser will be performed in combination with anti VEGF treatment</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of anti VEGF injections</measure>
    <time_frame>12months</time_frame>
    <description>as measured between baseline and M12</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Visual Acuity (Letters)</measure>
    <time_frame>12 months</time_frame>
    <description>As measured by the Early Treatment Diabetic Retinopathy Study (ETDRS)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in central macular thickness</measure>
    <time_frame>12 months</time_frame>
    <description>as measured between baseline and M12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cost of treatment</measure>
    <time_frame>12 months</time_frame>
    <description>as measured between baseline and M12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incremental cost-utility ratio</measure>
    <time_frame>12 months</time_frame>
    <description>as measured between baseline and M12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact on quality of life using standard score evolution</measure>
    <time_frame>12 months</time_frame>
    <description>as measured between baseline and M12</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of AEs/SAEs</measure>
    <time_frame>36 months</time_frame>
    <description>as measured between baseline and M36</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">270</enrollment>
  <condition>Macular Edema</condition>
  <condition>Diabetic Retinopathy</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Indocyanine green-Guided Targeted Laser photocoagulation combines routine procedures, that are, the detection of macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser verification of the effectiveness of the photothrombosis by OCT. Indocyanine green-Guided Targeted Laser photocoagulation is administered in combination with anti VEGF treatment</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham laser is administered at randomization visit and repeated if needed 3 month later in combination with anti VEGF treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Indocyanine green-Guided Targeted Laser photocoagulation</intervention_name>
    <description>Detection of macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser verification of the effectiveness of the photothrombosis by OCT.</description>
    <arm_group_label>Experimental Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham laser</intervention_name>
    <description>Therapeutic procedure used in ophthalmology</description>
    <arm_group_label>Control Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diabetic women and men ≥18 years&#xD;
&#xD;
          -  with visual acuity lower or equal than 20/32 ( ≤ 74 TaLaDME protocol_v1.2_12.07.2018&#xD;
             9/76 ETDRS letters)&#xD;
&#xD;
          -  with central retinal thickness of more than 300μm in Spectral Domain OCT (SD-OCT)&#xD;
             and/or presence of retro-foveal hard exudates&#xD;
&#xD;
          -  due to DME&#xD;
&#xD;
          -  with one or more macro-aneurysms with a diameter greater than 150 μm in the posterior&#xD;
             pole&#xD;
&#xD;
          -  with health insurance&#xD;
&#xD;
          -  who signed the written informed consent form&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Presence of age-related drusens or of a macular degeneration in one or both any eyes&#xD;
&#xD;
          -  Significant opacity of the ocular media that could contribute to decreased visual&#xD;
             acuity&#xD;
&#xD;
          -  macro-aneurysm(s) mainly responsible for the DME located less than 500μm from the&#xD;
             center of the fovea (i.e. within 1 disc radius of the fovea),&#xD;
&#xD;
          -  Steroids injection within the last 4 months&#xD;
&#xD;
          -  proliferative diabetic retinopathy requiring panretinal photocoagulation or associated&#xD;
             with posterior tractional retinal detachment that may be worsened by the use of&#xD;
             anti-VEGF therapy&#xD;
&#xD;
          -  myocardial infarction or stroke within the last 3 months&#xD;
&#xD;
          -  Cataract surgery within the last 3 months&#xD;
&#xD;
          -  Local treatment with prostaglandin&#xD;
&#xD;
          -  Women who are pregnant, breast feeding or of child bearing age without effective&#xD;
             contraception&#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>Michel Paques</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Hayet Serhane</last_name>
    <phone>0140021144</phone>
    <phone_ext>+33</phone_ext>
    <email>hserhane@15-20.fr</email>
  </overall_contact>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 20, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 23, 2018</study_first_posted>
  <last_update_submitted>November 21, 2018</last_update_submitted>
  <last_update_submitted_qc>November 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2018</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 Edema</mesh_term>
    <mesh_term>Retinal Diseases</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
    <mesh_term>Edema</mesh_term>
  </condition_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/NCT03751501
org study id: P18-01
nct id: NCT03751501
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Our hypothesis is that implementing laser photocoagulation (IGTL) as an adjunctive treatment
      to intravitreal injections should lead to a significant reduction in the need for
      intravitreal injections in patients with diabetic macular edema without adverse consequences
      for visual acuity.
This study will be French, multicenter parallel group, 2-arms, randomized, sham
      laser-controlled, double-blind trial evaluating the effect of IGTL as an adjunctive procedure
      to intravitreal injections in patients with DME.

      Acts which are the subject of the study: indocyanine green-Guided Targeted Laser
      photocoagulation (IGTL): this combines routine procedures, that are, the detection of
      macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser
      verification of the effectiveness of the photothrombosis by OCT.

      Study act: the treatment study includes a baseline laser treatment (experimental group) or
      sham laser (control group) at randomization, repeated if needed 3 month later, administered
      in combination with anti VEGF treatment, consisting of 3 monthly injections in the first 3
      months, and a maintenance phase with monthly visits where retreatment is administered as
      needed through a PRN regimen, based on morphological (retinal thickness on OCT) and
      functional (visual acuity) criteria.

      To evaluate the interest of IGTL in real conditions, the choice of the anti VEGF treatment
      used for intravitreal injection (Ranibizumab or Aflibercept, which have French marketing
      authorizations) is left to each investigator (equivalent therapeutic efficacy). Bevacizumab
      is ruled out due to its lower efficacy compared with Aflibercept among eyes with worse
      baseline VA, that represent the majority of the patients in our study. In addition,
      bevacizumab is currently off-label in France for DME If both eyes are eligible at the time of
      randomization, only one eye will be included and analyzed. However, the fellow eye will be
      treated with the randomization-assigned treatment and the testing will be performed on each
      eye.

      Risks and constraints involved in the study: these procedures are commonly done in
      ophthalmology care settings; no additional risk is expected due to the study.

      Expected benefits for the participants and for the company: These procedures are commonly
      done in ophthalmology care settings; no additional risk is expected due to the study.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Eligible participants will be randomized into one of the 2 study arms groups: "standard of care" group with sham laser or experimental group with laser.
Both group with laser or sham laser will be performed in combination with anti VEGF treatment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Number of anti VEGF injections
time frame: 12months
description: as measured between baseline and M12
measure: Change in Visual Acuity (Letters)
time frame: 12 months
description: As measured by the Early Treatment Diabetic Retinopathy Study (ETDRS)
measure: Change in central macular thickness
time frame: 12 months
description: as measured between baseline and M12
measure: Cost of treatment
time frame: 12 months
description: as measured between baseline and M12
measure: Incremental cost-utility ratio
time frame: 12 months
description: as measured between baseline and M12
measure: Impact on quality of life using standard score evolution
time frame: 12 months
description: as measured between baseline and M12
measure: Number of AEs/SAEs
time frame: 36 months
description: as measured between baseline and M36
arm group label: Experimental Group
arm group type: Experimental
description: Indocyanine green-Guided Targeted Laser photocoagulation combines routine procedures, that are, the detection of macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser verification of the effectiveness of the photothrombosis by OCT. Indocyanine green-Guided Targeted Laser photocoagulation is administered in combination with anti VEGF treatment
arm group label: Control Group
arm group type: Sham Comparator
description: Sham laser is administered at randomization visit and repeated if needed 3 month later in combination with anti VEGF treatment
intervention type: Procedure
intervention name: Indocyanine green-Guided Targeted Laser photocoagulation
description: Detection of macro-aneurysms by ICG angiography, laser photocoagulation and optional post-laser verification of the effectiveness of the photothrombosis by OCT.
arm group label: Experimental Group
intervention type: Procedure
intervention name: Sham laser
description: Therapeutic procedure used in ophthalmology
arm group label: Control Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michel Paques
role: Principal Investigator
affiliation: Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
last name: Hayet Serhane
phone: 0140021144
phone ext: +33
email: hserhane@15-20.fr
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Retinal Diseases
mesh term: Diabetic Retinopathy
mesh term: Edema