<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/NCT04462523</url>
  </required_header>
  <id_info>
    <org_study_id>The ADHERE Study</org_study_id>
    <nct_id>NCT04462523</nct_id>
  </id_info>
  <brief_title>DEXTENZA for the Treatment of Postoperative Pain and Inflammation Following Vitreo-retinal Surgery</brief_title>
  <official_title>Open-label, Single -Center, Prospective Study on the Efficacy and Safety of Intracanalicular Dexamethasone Insert 0.4mg (Dextenza) in the Treatment of Postoperative Pain and Inflammation Following Vitreo-retinal Surgery - The ADHERE Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Patrick R. Oellers, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ocular Therapeutix, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Retina Vitreous Surgeons of Central New York, PC</source>
  <oversight_info>
    <has_dmc>No</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>
      The purpose of this study is to evaluate efficacy and safety of Dextenza for the treatment of&#xD;
      postoperative pain and inflammation following vitreo-retinal surgery&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective, single-center, open-label, investigator-sponsored clinical study seeks to&#xD;
      investigate the outcomes of patients undergoing vitro-retinal surgery with the treatment of a&#xD;
      dexamethasone intracanalicular insert. All patients in the treatment groups will receive a&#xD;
      dexamethasone intracanalicular insert. There will be three experimental groups of patients,&#xD;
      varying that time of insertion. Ten patients will receive the dexamethasone intracanalicular&#xD;
      insert pre-operatively (1 week to 1 days prior to vitreo-retinal surgery). Ten patients will&#xD;
      receive dexamethasone intracanalicular insert on the day of surgery. Ten patients will&#xD;
      receive DEXTENZA insert Day 1 post-operatively. Ten patients will be prescribed standard of&#xD;
      care ophthalmic drops, Prednisolone Acetate, and no dexamethasone insert (control group). All&#xD;
      patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 3, 2020</start_date>
  <completion_date type="Actual">March 31, 2022</completion_date>
  <primary_completion_date type="Actual">March 31, 2022</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 (Outcomes Assessor)</masking>
    <masking_description>Masked Sub-investigators to exam subjects at each visit after clinical evaluation for cell and/or flare.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Mean cells as assessed by investigator in anterior chamber of the study eye</measure>
    <time_frame>Assessed at Day 14</time_frame>
    <description>As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean pain as reported by subject in the study eye: Visual Analog Scale</measure>
    <time_frame>Assessed at Day 28</time_frame>
    <description>As measured by Visual Analog Scale for Pain (VAS Pain) (0% to 100% Scale)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean anterior chamber flare</measure>
    <time_frame>Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56</time_frame>
    <description>As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to absence of cells</measure>
    <time_frame>Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56</time_frame>
    <description>As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to absence of pain</measure>
    <time_frame>Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56</time_frame>
    <description>As measure by Visual Analog Scale for Pain (VAS Pain) (0% to 100% Scale)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of rescue treatment</measure>
    <time_frame>Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56</time_frame>
    <description>As measure by Concomitant Medications as rescue therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Dextenza ease of insertion</measure>
    <time_frame>Assessed at Day 1</time_frame>
    <description>As measured by Ease of Use Survey (0=very easy to 10=very hard)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Vitreo-Retinal Surgery</condition>
  <arm_group>
    <arm_group_label>Group 1 Pre-surgery Dextenza insert</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten patients will receive the dexamethasone intracanalicular insert pre-operatively (1 week to 1 days prior to vitreo-retinal surgery). All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 2 Surgery Day Dextenza insert</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten patients will receive dexamethasone intracanalicular insert on the day of surgery. All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3 Post op Day 1 Dextenza insert</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Ten patients will receive DEXTENZA insert Day 1 post-operatively. All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 4 Topical steroid</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Ten patients will be prescribed standard of care ophthalmic drops, Prednisolone Acetate, and no dexamethasone insert (control group). All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextenza 0.4Mg Ophthalmic Insert</intervention_name>
    <description>The insert, containing 0.4 mg of active pharmaceutical product, is placed within the canaliculus to provide a sustained and tapered delivery of drug to the ocular surface over 30 days after a one-time insertion. The attributes of the insert reduce the risks for improper corticosteroid tapering and unwanted peaks and troughs in drug concentration.</description>
    <arm_group_label>Group 1 Pre-surgery Dextenza insert</arm_group_label>
    <arm_group_label>Group 2 Surgery Day Dextenza insert</arm_group_label>
    <arm_group_label>Group 3 Post op Day 1 Dextenza insert</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topical Prednisolone</intervention_name>
    <description>Standard of care topical drop treatment</description>
    <arm_group_label>Group 4 Topical steroid</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Any adult patient age 18-99 years who is planned to undergo vitreo-retinal surgery&#xD;
             (pars plana vitrectomy with or without scleral buckle).&#xD;
&#xD;
          -  If both eyes are involved, both eyes would be eligible for the study.&#xD;
&#xD;
          -  Willing and able to comply with clinic visits and study related procedures.&#xD;
&#xD;
          -  Willing and able to sign the informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients under age 18.&#xD;
&#xD;
          -  Patients who are pregnant (must be ruled out in women of child-bearing age with&#xD;
             pregnancy test).&#xD;
&#xD;
          -  Active infectious ocular or systemic disease.&#xD;
&#xD;
          -  Patients with active infectious ocular or extraocular disease.&#xD;
&#xD;
          -  Patients actively treated with local or systemic immunosuppression&#xD;
&#xD;
          -  Use of the following anti-inflammatory or immunomodulating agents (e.g., cyclosporine)&#xD;
             systemically, or in the study eye, for the duration of the study (excluding&#xD;
             inhalants). Washout periods for medications prior to surgery are as follows:&#xD;
&#xD;
          -  Systemic corticosteroids - 2 weeks (see exception 5c)&#xD;
&#xD;
          -  Systemic NSAID over 375 mg per day - 2 weeks&#xD;
&#xD;
          -  Periocular/intraocular injection of any corticosteroid solution - 4 weeks (see&#xD;
             exception 5b)&#xD;
&#xD;
          -  Corticosteroid depot/implant in the study eye - 2 months&#xD;
&#xD;
          -  Topical ocular corticosteroid - 7 days&#xD;
&#xD;
          -  Topical ocular NSAID - 7 days&#xD;
&#xD;
          -  Intraoperatively used intraocular steroid (i.e. intravitreal triamcinolone, that is&#xD;
             used to transiently highlight the vitreous and removed during vitrectomy) is&#xD;
             permissible in study eye.&#xD;
&#xD;
          -  Intraoperatively or perioperatively used systemic steroid for the purpose of general&#xD;
             anesthesia (as administered by the treating anesthesiologist) is permissible.&#xD;
&#xD;
          -  Patients with systemic illness involving abnormalities of the&#xD;
             hypothalamic-pituitary-adrenal axis; patients with primary adrenocortical&#xD;
             insufficiency or adrenocortical hyperfunction.&#xD;
&#xD;
          -  Patients with known hypersensitivity to Dexamethasone.&#xD;
&#xD;
          -  Patients with uncontrolled glaucoma.&#xD;
&#xD;
          -  Patients with severe disease that warrants critical attention, deemed unsafe for the&#xD;
             study by the investigator.&#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>Retina Vitreous Surgeons of Central New York, PC</name>
      <address>
        <city>Liverpool</city>
        <state>New York</state>
        <zip>13088</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Retina Vitreous Surgeons of Central New York, PC</investigator_affiliation>
    <investigator_full_name>Patrick R. Oellers, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</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/NCT04462523
org study id: The ADHERE Study
nct id: NCT04462523
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate efficacy and safety of Dextenza for the treatment of
      postoperative pain and inflammation following vitreo-retinal surgery
This prospective, single-center, open-label, investigator-sponsored clinical study seeks to
      investigate the outcomes of patients undergoing vitro-retinal surgery with the treatment of a
      dexamethasone intracanalicular insert. All patients in the treatment groups will receive a
      dexamethasone intracanalicular insert. There will be three experimental groups of patients,
      varying that time of insertion. Ten patients will receive the dexamethasone intracanalicular
      insert pre-operatively (1 week to 1 days prior to vitreo-retinal surgery). Ten patients will
      receive dexamethasone intracanalicular insert on the day of surgery. Ten patients will
      receive DEXTENZA insert Day 1 post-operatively. Ten patients will be prescribed standard of
      care ophthalmic drops, Prednisolone Acetate, and no dexamethasone insert (control group). All
      patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: Masked Sub-investigators to exam subjects at each visit after clinical evaluation for cell and/or flare.
measure: Mean cells as assessed by investigator in anterior chamber of the study eye
time frame: Assessed at Day 14
description: As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)
measure: Mean pain as reported by subject in the study eye: Visual Analog Scale
time frame: Assessed at Day 28
description: As measured by Visual Analog Scale for Pain (VAS Pain) (0% to 100% Scale)
measure: Mean anterior chamber flare
time frame: Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56
description: As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)
measure: Time to absence of cells
time frame: Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56
description: As measure by Standardization of Uveitis Nomenclature (SUN Scale) (Grade 0 to Grade 4+)
measure: Time to absence of pain
time frame: Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56
description: As measure by Visual Analog Scale for Pain (VAS Pain) (0% to 100% Scale)
measure: Proportion of rescue treatment
time frame: Assessed at Screening, Day 1, Day 4, Day 14, Day 28 and Day 56
description: As measure by Concomitant Medications as rescue therapy
measure: Assessment of Dextenza ease of insertion
time frame: Assessed at Day 1
description: As measured by Ease of Use Survey (0=very easy to 10=very hard)
arm group label: Group 1 Pre-surgery Dextenza insert
arm group type: Experimental
description: Ten patients will receive the dexamethasone intracanalicular insert pre-operatively (1 week to 1 days prior to vitreo-retinal surgery). All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.
arm group label: Group 2 Surgery Day Dextenza insert
arm group type: Experimental
description: Ten patients will receive dexamethasone intracanalicular insert on the day of surgery. All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.
arm group label: Group 3 Post op Day 1 Dextenza insert
arm group type: Experimental
description: Ten patients will receive DEXTENZA insert Day 1 post-operatively. All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops
arm group label: Group 4 Topical steroid
arm group type: Active Comparator
description: Ten patients will be prescribed standard of care ophthalmic drops, Prednisolone Acetate, and no dexamethasone insert (control group). All patients no matter what cohort will receive Gentamicin, antibiotic ophthalmic drops.
intervention type: Drug
intervention name: Dextenza 0.4Mg Ophthalmic Insert
description: The insert, containing 0.4 mg of active pharmaceutical product, is placed within the canaliculus to provide a sustained and tapered delivery of drug to the ocular surface over 30 days after a one-time insertion. The attributes of the insert reduce the risks for improper corticosteroid tapering and unwanted peaks and troughs in drug concentration.
arm group label: Group 1 Pre-surgery Dextenza insert
arm group label: Group 2 Surgery Day Dextenza insert
arm group label: Group 3 Post op Day 1 Dextenza insert
intervention type: Drug
intervention name: Topical Prednisolone
description: Standard of care topical drop treatment
arm group label: Group 4 Topical steroid
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Retina Vitreous Surgeons of Central New York, PC
investigator full name: Patrick R. Oellers, MD
investigator title: Principal Investigator
mesh term: Inflammation
mesh term: Pain, Postoperative
mesh term: Prednisolone