<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/NCT04411693</url>
  </required_header>
  <id_info>
    <org_study_id>ALLER1908JE</org_study_id>
    <nct_id>NCT04411693</nct_id>
  </id_info>
  <brief_title>Comparative Study of Dexamethasone Implant to Intravitreal Aflibercept in Subjects With Diabetic Macular Edema</brief_title>
  <acronym>PRECISION</acronym>
  <official_title>Prospective Randomized Comparative Trial for Combination Dexamethasone Implant With PRN Anti-VEGF Therapy to Anti-VEGF Therapy Alone in Treatment Resistant DME: Informing the Role for Imaging Biomarkers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Allergan</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Cleveland Clinic</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</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>
      This study is an interventional, prospective randomized study comparing the dexamethasone&#xD;
      implant to intravitreal aflibercept. Subjects will have an initial single injection of&#xD;
      aflibercept and will be randomized if diabetic macular edema persists. Each subject will be&#xD;
      evaluated for 6 months following randomization. Thus, the study duration will be 12 months&#xD;
      plus the recruitment period.&#xD;
&#xD;
      Subjects will be evaluated every month for safety, efficacy as measured by SDOCT and best&#xD;
      corrected visual acuity (BCVA) using the Electronic Early Treatment Diabetic Retinopathy&#xD;
      Study (E-ETDRS) protocol. In addition, ultra-widefield angiography will be performed at&#xD;
      run-in visit, baseline, month 3, and month 6.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 10, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The mean change in central subfield thickness</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of injections</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in BCVA</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in leakage index</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ischemic index</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in microaneurysm counts</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in ellipsoid zone integrity</measure>
    <time_frame>6 months</time_frame>
    <description>Change in ellipsoid zone integrity as measured by EZ-RPE central subfield thickness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in intraretinal fluid volume</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in DRSS</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of ocular and non-ocular adverse events and serious adverse events</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">23</enrollment>
  <condition>Diabetic Macular Edema</condition>
  <arm_group>
    <arm_group_label>Group A: Intravitreal Dexamethasone Implant</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in this arm will be given intravitreal Dexamethasone implant injection at month 0. PRN intravitreal Dexamethasone implant injections will be given for persistent edema, if it has been 10 weeks or more since last implant injection. If it has been less than 10 weeks since last implant injection, subjects will receive PRN intravitreal Aflibercept for persistent edema.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: Intravitreal Aflibercept</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects in this arm will be given Intravitreal aflibercept at month 0. PRN intravitreal Aflibercept will be given at months 1-6 for persistent edema.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone implant</intervention_name>
    <description>A sustained-release drug delivery system containing 0.7 mg of Dexamethasone. Implant is administered by intravitreal injection.</description>
    <arm_group_label>Group A: Intravitreal Dexamethasone Implant</arm_group_label>
    <other_name>Ozurdex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aflibercept</intervention_name>
    <description>A single dose, 2mg, drug administered by intravitreal injection.</description>
    <arm_group_label>Group A: Intravitreal Dexamethasone Implant</arm_group_label>
    <arm_group_label>Group B: Intravitreal Aflibercept</arm_group_label>
    <other_name>Eylea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent.&#xD;
&#xD;
          2. Men and women ≥ 18 years of age.&#xD;
&#xD;
          3. Foveal-involving retinal edema secondary to DME based on investigator review of&#xD;
             SD-OCT.&#xD;
&#xD;
          4. Central subfield thickness on SDOCT of greater than or equal to 325 microns on&#xD;
             Spectralis or 300 microns on Cirrus.&#xD;
&#xD;
          5. E-ETDRS best-corrected visual acuity of 20/400 or better in the study eye.&#xD;
&#xD;
          6. Willing, committed, and able to return for ALL clinic visits and complete all study&#xD;
             related procedures.&#xD;
&#xD;
          7. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by&#xD;
             the person administering the informed consent or a family member) understand and&#xD;
             willing to sign the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any prior or concomitant therapy with another investigational agent to treat DME in&#xD;
             the study eye.&#xD;
&#xD;
          2. Prior panretinal photocoagulation in the study eye.&#xD;
&#xD;
          3. Prior intravitreal anti-VEGF therapy in the study eye.&#xD;
&#xD;
          4. Prior focal/grid laser photocoagulation in the study eye.&#xD;
&#xD;
          5. Prior history of intravitreal steroid therapy in the study eye.&#xD;
&#xD;
          6. Any history of severe allergy to fluorescein sodium (e.g., anaphylaxis, difficulty&#xD;
             breathing) or other reason that the patient is unable to undergo fluorescein&#xD;
             angiography (e.g., inability to get vascular access, unable to tolerate procedure). If&#xD;
             allergy is mild and investigator believes can be pretreated with diphenhydramine to&#xD;
             avoid allergic response, this is not an exclusion to enrollment.&#xD;
&#xD;
          7. Uncontrolled glaucoma at baseline evaluation (defined as intraocular pressure ≥25 mmHg&#xD;
             despite treatment with anti-glaucoma medication) in the study eye and/or cup-to-disc&#xD;
             ratio greater or equal to 0.8.&#xD;
&#xD;
          8. Active intraocular inflammation in either eye.&#xD;
&#xD;
          9. Active ocular or periocular infection in either eye.&#xD;
&#xD;
         10. Torn or ruptured posterior lens capsule in study eye. Laser capsulotomy is not a&#xD;
             contraindication.&#xD;
&#xD;
         11. Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up&#xD;
             to 3 months prior to first dose, and will not be allowed during the study.&#xD;
&#xD;
         12. Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery&#xD;
             as determined by the investigator on clinical exam and ultra-widefield angiography, in&#xD;
             study eye.&#xD;
&#xD;
         13. Presence of other causes of macular edema, including pathologic myopia (spherical&#xD;
             equivalent of -8 diopters or more negative, or axial length of 25 mm or more), ocular&#xD;
             histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal&#xD;
             neovascularization, age-related macular degeneration or multifocal choroiditis in the&#xD;
             study eye. Epiretinal membranes are allowed.&#xD;
&#xD;
         14. Presence of macula-threatening traction retinal detachment in the study eye.&#xD;
&#xD;
         15. Prior vitrectomy in the study eye.&#xD;
&#xD;
         16. History of retinal detachment or treatment or surgery for retinal detachment in the&#xD;
             study eye.&#xD;
&#xD;
         17. Any history of macular hole of stage 2 and above in the study eye.&#xD;
&#xD;
         18. Any intraocular or periocular surgery within 3 months of Day 1 in the study eye,&#xD;
             except lid surgery, which may not have taken place within 1 month of day 1, as long as&#xD;
             it's unlikely to interfere with the injection.&#xD;
&#xD;
         19. Prior trabeculectomy or other filtration surgery in the study eye.&#xD;
&#xD;
         20. Any ocular or periocular infection within the last 2 weeks prior to Screening in&#xD;
             either eye.&#xD;
&#xD;
         21. Any history of uveitis in either eye.&#xD;
&#xD;
         22. Active scleritis or episcleritis in either eye.&#xD;
&#xD;
         23. Presence or history of scleromalacia in either eye.&#xD;
&#xD;
         24. Aphakia in the study eye.&#xD;
&#xD;
         25. Previous therapeutic radiation in the region of the study eye.&#xD;
&#xD;
         26. History of corneal transplant or corneal dystrophy in the study eye.&#xD;
&#xD;
         27. Significant media opacities, including cataract, in the study eye which might&#xD;
             interfere with visual acuity, assessment of safety, or fundus photography.&#xD;
&#xD;
         28. Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the&#xD;
             opinion of the investigator, could require either medical or surgical intervention&#xD;
             during the study period.&#xD;
&#xD;
         29. Any concurrent ocular condition in the study eye which, in the opinion of the&#xD;
             investigator, could either increase the risk to the subject beyond what is to be&#xD;
             expected from standard procedures of intraocular injection, or which otherwise may&#xD;
             interfere with the injection procedure or with evaluation of efficacy or safety.&#xD;
&#xD;
         30. Participation as a subject in any clinical study within the 12 weeks prior to Day 1.&#xD;
&#xD;
         31. Any systemic therapy with an investigational agent in the past 3 months prior to Day&#xD;
             1.&#xD;
&#xD;
         32. Any history of allergy to povidone iodine.&#xD;
&#xD;
         33. Pregnant or breast-feeding women&#xD;
&#xD;
         34. Women of childbearing potential* who are unwilling to practice adequate contraception&#xD;
             during the study (adequate contraceptive measures include stable use of oral&#xD;
             contraceptives or other prescription pharmaceutical contraceptives for 2 or more&#xD;
             menstrual cycles prior to screening; intrauterine device [IUD]; bilateral tubal&#xD;
             ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or diaphragm&#xD;
             plus contraceptive sponge, foam, or jelly) *Postmenopausal women must be amenorrheic&#xD;
             for at least 12 months in order not to be considered of child bearing potential.&#xD;
             Pregnancy testing and contraception are not required for women with documented&#xD;
             hysterectomy or tubal ligation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Retina Consultants of Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>May 20, 2023</last_update_submitted>
  <last_update_submitted_qc>May 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Cleveland Clinic</investigator_affiliation>
    <investigator_full_name>Justis Ehlers</investigator_full_name>
    <investigator_title>The Norman C. and Donna L. Harbert Endowed Chair of Ophthalmic Research</investigator_title>
  </responsible_party>
  <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>Dexamethasone</mesh_term>
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT04411693
org study id: ALLER1908JE
nct id: NCT04411693
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This study is an interventional, prospective randomized study comparing the dexamethasone
      implant to intravitreal aflibercept. Subjects will have an initial single injection of
      aflibercept and will be randomized if diabetic macular edema persists. Each subject will be
      evaluated for 6 months following randomization. Thus, the study duration will be 12 months
      plus the recruitment period.

      Subjects will be evaluated every month for safety, efficacy as measured by SDOCT and best
      corrected visual acuity (BCVA) using the Electronic Early Treatment Diabetic Retinopathy
      Study (E-ETDRS) protocol. In addition, ultra-widefield angiography will be performed at
      run-in visit, baseline, month 3, and month 6.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The mean change in central subfield thickness
time frame: 6 months
measure: Number of injections
time frame: 6 months
measure: Change in BCVA
time frame: 6 months
measure: Change in leakage index
time frame: 6 months
measure: Change in ischemic index
time frame: 6 months
measure: Change in microaneurysm counts
time frame: 6 months
measure: Change in ellipsoid zone integrity
time frame: 6 months
description: Change in ellipsoid zone integrity as measured by EZ-RPE central subfield thickness
measure: Change in intraretinal fluid volume
time frame: 6 months
measure: Change in DRSS
time frame: 6 months
measure: The incidence and severity of ocular and non-ocular adverse events and serious adverse events
time frame: 6 months
arm group label: Group A: Intravitreal Dexamethasone Implant
arm group type: Active Comparator
description: Subjects in this arm will be given intravitreal Dexamethasone implant injection at month 0. PRN intravitreal Dexamethasone implant injections will be given for persistent edema, if it has been 10 weeks or more since last implant injection. If it has been less than 10 weeks since last implant injection, subjects will receive PRN intravitreal Aflibercept for persistent edema.
arm group label: Group B: Intravitreal Aflibercept
arm group type: Active Comparator
description: Subjects in this arm will be given Intravitreal aflibercept at month 0. PRN intravitreal Aflibercept will be given at months 1-6 for persistent edema.
intervention type: Drug
intervention name: Dexamethasone implant
description: A sustained-release drug delivery system containing 0.7 mg of Dexamethasone. Implant is administered by intravitreal injection.
arm group label: Group A: Intravitreal Dexamethasone Implant
other name: Ozurdex
intervention type: Drug
intervention name: Aflibercept
description: A single dose, 2mg, drug administered by intravitreal injection.
arm group label: Group A: Intravitreal Dexamethasone Implant
arm group label: Group B: Intravitreal Aflibercept
other name: Eylea
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: The Cleveland Clinic
investigator full name: Justis Ehlers
investigator title: The Norman C. and Donna L. Harbert Endowed Chair of Ophthalmic Research
mesh term: Macular Edema
mesh term: Edema
mesh term: Dexamethasone
mesh term: Aflibercept
sharing ipd: No