<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/NCT02229175</url>
  </required_header>
  <id_info>
    <org_study_id>14-14153</org_study_id>
    <nct_id>NCT02229175</nct_id>
  </id_info>
  <brief_title>Laser vs Bevacizumab Injection Alone in Treatment of Diabetic Macular Edema</brief_title>
  <official_title>Comparison of Subvisible Retinal Laser Therapy With Intravitreal Bevacizumab in Treatment of Diabetic Macular Edema</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Currently, diabetic macular edema is treated is through injection of a medications such as&#xD;
      off-label bevacizumab, which decreases the swelling in the retina. These injections are&#xD;
      sometimes required monthly until the condition is controlled. Recently, there have been some&#xD;
      new FDA approved treatments using laser that decrease the swelling. These approximately ten&#xD;
      minute treatments do not require injections and don't cause permanent damage to the eye, and&#xD;
      they may decrease the number of injections one needs to get to treat diabetic macular edema&#xD;
      (DME).&#xD;
&#xD;
      The purpose of this randomized clinical trial is to determine whether subvisible laser in&#xD;
      combination with intravitreal bevacizumab is non-inferior compared to current standard of&#xD;
      care (intravitreal bevacizumab alone) in achieving favorable outcomes for visual acuity, mean&#xD;
      macular thickness, and patient quality of life, and has fewer needed intravitreal bevacizumab&#xD;
      injections throughout the course of the 12 month study period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The patient is randomized into one of two study groups described below.&#xD;
&#xD;
        -  Group 1: Intravitreal bevacizumab (IVB) will be administered at the first 3 monthly&#xD;
           visits and subvisible laser treatment will be administered at the first visit. The the&#xD;
           patient will undergo monthly visits, as he/she would with standard of care treatment,&#xD;
           allowing for retreatment with monthly IVB and laser treatment every 3 months if defined&#xD;
           retreatment criteria are met, as determined by a physician.&#xD;
&#xD;
        -  Group 2: Intravitreal bevacizumab (IVB) will be administered at the first 3 monthly&#xD;
           visits. The patient will then undergo monthly exams, as he or she would with standard of&#xD;
           care treatment, allowing for retreatment with monthly IVB if defined retreatment&#xD;
           criteria are met, as determined by a physician. The patient may also undergo sham laser&#xD;
           treatment (he/she will be placed in front of laser but no laser will be activated) so&#xD;
           that the patient isn't made aware of which treatment group he/she is a part of.&#xD;
&#xD;
      Other data that will be collected throughout the study at monthly examinations:&#xD;
&#xD;
        -  Monthly Snellen Visual acuity test&#xD;
&#xD;
        -  Monthly spectral-domain optical coherence tomography (SD-OCT) imaging using standard&#xD;
           clinic protocol monthly&#xD;
&#xD;
        -  Standard clinic diabetic montage Fundus photos at months 0,6,12&#xD;
&#xD;
        -  Fluorescein angiography at months 0, 6, 12&#xD;
&#xD;
      The subjects' visit schedules will be the same as for routine standard of care for the IVB&#xD;
      injection procedure. There are no additional appointments for this study.&#xD;
&#xD;
      All study procedures will be done at San Francisco General Hospital&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study not feasible with current resources.&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 1, 2021</start_date>
  <completion_date type="Anticipated">January 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">January 1, 2026</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Retinal thickness</measure>
    <time_frame>12 months</time_frame>
    <description>Change in retinal thickness on SD-OCT from baseline to 12 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Visual Acuity</measure>
    <time_frame>12 months</time_frame>
    <description>Change in Snellen visual acuity from baseline to 12 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of injections of bevacizumab needed</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>IVB + laser</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravitreal bevacizumab (IVB) will be administered at baseline, month 1, and month 2, consistent with previous DME trials. Subvisible laser treatment will be administered at baseline. Patients will then undergo monthly surveillance, as they would with standard of care treatment, allowing for retreatment with monthly IVB and laser therapy every 3 months if defined retreatment criteria are met, as described below.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IVB only</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>IVB monthly at baseline, month 1, and month 2. Patients will then undergo monthly surveillance, as they would with standard of care treatment, allowing for retreatment with monthly IVB if defined retreatment criteria are met, as described below. Patients will also undergo sham laser treatment (patient will be placed in front of laser but no laser will be activated) to mask the patient to the treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>bevacizumab</intervention_name>
    <description>intravitreal injections of antibodies inhibiting vascular endothelial growth factor</description>
    <arm_group_label>IVB + laser</arm_group_label>
    <arm_group_label>IVB only</arm_group_label>
    <other_name>Avastin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>PASCAL Endpoint Management (EpM) laser treatment</intervention_name>
    <description>This is an algorithm that is included in the PASCAL 577 mm yellow laser system (Topcon, Santa Clara, CA). This is FDA-approved for treatment of diabetic retinopathy and diabetic macular edema.</description>
    <arm_group_label>IVB + laser</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Inclusion criteria include adults ≥ 18 years with type 1 or 2 diabetes mellitus with&#xD;
             DME secondary to diabetes mellitus involving the center of the macula in the study eye&#xD;
             and with a decrease in vision is determined to be primarily the result of DME in the&#xD;
             study eye. The study eye must have a BCVA ETDRS letter score of 50 to 24 (20/30 to&#xD;
             20/320) in the study eye. The patient should be on a stable medical diabetic regimen&#xD;
             that is not expected to change.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients are excluded if they have had laser photocoagulation (panretinal or macular)&#xD;
             in the study eye within 90 days of Day 1, more than two previous macular laser&#xD;
             treatments in the study eye, previous use of intraocular or periocular corticosteroids&#xD;
             in the study eye within 90 days of Day 1, previous treatment with antiangiogenic drugs&#xD;
             in either eye (pegaptanib sodium, bevacizumab, ranibizumab, or aflibercept) within 45&#xD;
             days of Day 1, active proliferative diabetic retinopathy (PDR) in the study eye, with&#xD;
             the exception of inactive, regressed PDR, uncontrolled diabetes mellitus, as defined&#xD;
             by HbA1c &gt; 12%, or a patient who is functionally monocular, as defined by the&#xD;
             clinician or vision worse than 20/400 in the fellow eye even if that eye is otherwise&#xD;
             eligible for the study.&#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>Jay Stewart, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniel Chao, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Diego</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Catherine Psaras, BA</last_name>
    <role>Study Director</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>August 14, 2014</study_first_submitted>
  <study_first_submitted_qc>August 27, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 1, 2014</study_first_posted>
  <last_update_submitted>July 29, 2020</last_update_submitted>
  <last_update_submitted_qc>July 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diabetic Macular Edema</keyword>
  <keyword>Diabetic Retinopathy</keyword>
  <keyword>Type 1 Diabetes</keyword>
  <keyword>Type 2 Diabetes</keyword>
  <keyword>Macular Edema</keyword>
  <keyword>bevacizumab</keyword>
  <keyword>intravitreal injection</keyword>
  <keyword>Avastin</keyword>
  <keyword>PASCAL Endpoint Management (EpM) system</keyword>
  <keyword>Subthreshold focal laser treatments</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Bevacizumab</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/NCT02229175
org study id: 14-14153
nct id: NCT02229175
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Currently, diabetic macular edema is treated is through injection of a medications such as
      off-label bevacizumab, which decreases the swelling in the retina. These injections are
      sometimes required monthly until the condition is controlled. Recently, there have been some
      new FDA approved treatments using laser that decrease the swelling. These approximately ten
      minute treatments do not require injections and don't cause permanent damage to the eye, and
      they may decrease the number of injections one needs to get to treat diabetic macular edema
      (DME).

      The purpose of this randomized clinical trial is to determine whether subvisible laser in
      combination with intravitreal bevacizumab is non-inferior compared to current standard of
      care (intravitreal bevacizumab alone) in achieving favorable outcomes for visual acuity, mean
      macular thickness, and patient quality of life, and has fewer needed intravitreal bevacizumab
      injections throughout the course of the 12 month study period.
The patient is randomized into one of two study groups described below.

        -  Group 1: Intravitreal bevacizumab (IVB) will be administered at the first 3 monthly
           visits and subvisible laser treatment will be administered at the first visit. The the
           patient will undergo monthly visits, as he/she would with standard of care treatment,
           allowing for retreatment with monthly IVB and laser treatment every 3 months if defined
           retreatment criteria are met, as determined by a physician.

        -  Group 2: Intravitreal bevacizumab (IVB) will be administered at the first 3 monthly
           visits. The patient will then undergo monthly exams, as he or she would with standard of
           care treatment, allowing for retreatment with monthly IVB if defined retreatment
           criteria are met, as determined by a physician. The patient may also undergo sham laser
           treatment (he/she will be placed in front of laser but no laser will be activated) so
           that the patient isn't made aware of which treatment group he/she is a part of.

      Other data that will be collected throughout the study at monthly examinations:

        -  Monthly Snellen Visual acuity test

        -  Monthly spectral-domain optical coherence tomography (SD-OCT) imaging using standard
           clinic protocol monthly

        -  Standard clinic diabetic montage Fundus photos at months 0,6,12

        -  Fluorescein angiography at months 0, 6, 12

      The subjects' visit schedules will be the same as for routine standard of care for the IVB
      injection procedure. There are no additional appointments for this study.

      All study procedures will be done at San Francisco General Hospital
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Retinal thickness
time frame: 12 months
description: Change in retinal thickness on SD-OCT from baseline to 12 months.
measure: Visual Acuity
time frame: 12 months
description: Change in Snellen visual acuity from baseline to 12 months.
measure: Number of injections of bevacizumab needed
time frame: 12 months
arm group label: IVB + laser
arm group type: Experimental
description: Intravitreal bevacizumab (IVB) will be administered at baseline, month 1, and month 2, consistent with previous DME trials. Subvisible laser treatment will be administered at baseline. Patients will then undergo monthly surveillance, as they would with standard of care treatment, allowing for retreatment with monthly IVB and laser therapy every 3 months if defined retreatment criteria are met, as described below.
arm group label: IVB only
arm group type: Active Comparator
description: IVB monthly at baseline, month 1, and month 2. Patients will then undergo monthly surveillance, as they would with standard of care treatment, allowing for retreatment with monthly IVB if defined retreatment criteria are met, as described below. Patients will also undergo sham laser treatment (patient will be placed in front of laser but no laser will be activated) to mask the patient to the treatment.
intervention type: Drug
intervention name: bevacizumab
description: intravitreal injections of antibodies inhibiting vascular endothelial growth factor
arm group label: IVB + laser
arm group label: IVB only
other name: Avastin
intervention type: Device
intervention name: PASCAL Endpoint Management (EpM) laser treatment
description: This is an algorithm that is included in the PASCAL 577 mm yellow laser system (Topcon, Santa Clara, CA). This is FDA-approved for treatment of diabetic retinopathy and diabetic macular edema.
arm group label: IVB + laser
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jay Stewart, MD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Daniel Chao, MD, PhD
role: Principal Investigator
affiliation: University of California, San Diego
last name: Catherine Psaras, BA
role: Study Director
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Macular Edema
mesh term: Edema
mesh term: Bevacizumab