<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/NCT01695668</url>
  </required_header>
  <id_info>
    <org_study_id>Lotemax_00045815</org_study_id>
    <nct_id>NCT01695668</nct_id>
  </id_info>
  <brief_title>Treatment of Ocular Graft-versus-Host Disease (GVHD) With Topical Loteprednol Etabonate 0.5%</brief_title>
  <acronym>Lotemax_BMT</acronym>
  <official_title>Treatment of Ocular Graft-versus-Host Disease (GVHD) With Topical Loteprednol</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Michigan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bausch &amp; Lomb Incorporated</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Michigan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to:&#xD;
&#xD;
        1. Evaluate the safety and efficacy of a steroid eye drop (Lotemax) in patients who have&#xD;
           been diagnosed with graft-versus-host disease (GVHD), which is a complication that may&#xD;
           occur after bone marrow transplant where the newly transplanted material attacks the&#xD;
           patient's body and may cause eye dryness.&#xD;
&#xD;
        2. Assess the safety and efficacy of Lotemax in decreasing the eye's reaction to the&#xD;
           process in GVHD before the patient undergoes bone marrow transplant.&#xD;
&#xD;
        3. Compare how well Lotemax works in decreasing the process in GVHD with an&#xD;
           immunosuppressive eye drop (Restasis), which has been commonly used in the treatment of&#xD;
           this condition.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Allogeneic bone marrow or peripheral stem cell transplantation result in Graft-versus-Host&#xD;
      disease. Ocular symptoms may be the first presentation of GVHD and may be seen in the absence&#xD;
      of systemic manifestations. GVHD is categorized into acute and chronic forms as defined by&#xD;
      100 days after the transplant. Acute GVHD is characterized by dermatitis, hepatitis, and&#xD;
      enteritis. Chronic GVHD involves the skin, mouth, liver, gastrointestinal tract, lungs, and&#xD;
      eyes. Ocular GVHD is a common cause of dry eye symptoms in patients who have undergone bone&#xD;
      marrow transplant (BMT), and can be defined as ocular surface disease in the context of GVHD.&#xD;
      Dry eyes develop in 76% of acute GVHD patients and between 62.5% and 81.8% of chronic GVHD&#xD;
      patients. Current treatment for ocular GVHD includes topical cyclosporine 0.05% (Restasis,&#xD;
      Allergan). Topical loteprednol etabonate 0.5% (Lotemax, Bausch and Lomb) has been shown to be&#xD;
      safe and efficacious in treatment of inflammatory ocular disorders, but has not been&#xD;
      prospectively studied in ocular GVHD.&#xD;
&#xD;
      2. Hypothesis: We anticipate that topical loteprednol etabonate 0.5% will be safe and&#xD;
      efficacious in treatment of ocular GVHD patients, and would add to the armamentarium of&#xD;
      therapeutics for this disease. Further, by following the natural progression of the disease&#xD;
      prior to a patient's Bone Marrow Transplant (BMT), we may elucidate a new standard of care&#xD;
      for these patients - one that involves referral to an ophthalmologist before ocular GVHD&#xD;
      symptoms arise.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2011</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">September 2013</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression of Dry Eye Severity</measure>
    <time_frame>1 year</time_frame>
    <description>Dry eye is one of the major symptoms of ocular GVHD in bone-marrow transplant recipients, worsening of dry eye symptoms may be indicative of worsening ocular GVHD conditions.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">75</enrollment>
  <condition>Dry Eyes</condition>
  <arm_group>
    <arm_group_label>Lotemax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Loteprednol Etabonate 0.5%</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Restasis</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Cyclosporine</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lotemax</intervention_name>
    <description>Ophthalmic corticosteroid. It decreases inflammation of the eye</description>
    <arm_group_label>Lotemax</arm_group_label>
    <other_name>Loteprednol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Restasis</intervention_name>
    <description>Restasis is an immunosuppressive agent. Cyclosporine may reduce inflammation in the eye.</description>
    <arm_group_label>Restasis</arm_group_label>
    <other_name>cyclosporine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Scheduled for allogenic bone marrow transplant&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Allergic reaction to loteprednol or cyclosporine, previous allogenic transplant&#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>Shahzad Mian, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Michigan</affiliation>
  </overall_official>
  <verification_date>August 2015</verification_date>
  <study_first_submitted>September 25, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>January 16, 2015</results_first_submitted>
  <results_first_submitted_qc>August 24, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">September 24, 2015</results_first_posted>
  <last_update_submitted>August 24, 2015</last_update_submitted>
  <last_update_submitted_qc>August 24, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 24, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Michigan</investigator_affiliation>
    <investigator_full_name>Shahzad Mian</investigator_full_name>
    <investigator_title>Terry J. Bergstrom Professor for Resident Education, Associate Professor, Cornea and External Disease</investigator_title>
  </responsible_party>
  <keyword>Graft versus Host Disease (GVHD)</keyword>
  <keyword>dry eyes</keyword>
  <keyword>Bone marrow transplant (BMT)</keyword>
  <keyword>Restasis</keyword>
  <keyword>Lotemax</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dry Eye Syndromes</mesh_term>
    <mesh_term>Graft vs Host Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Loteprednol Etabonate</mesh_term>
    <mesh_term>Cyclosporine</mesh_term>
    <mesh_term>Cyclosporins</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Lotemax</title>
          <description>Loteprednol Etabonate 0.5%</description>
        </group>
        <group group_id="P2">
          <title>Restasis</title>
          <description>Cyclosporine</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="37"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lotemax</title>
          <description>Loteprednol Etabonate 0.5%</description>
        </group>
        <group group_id="B2">
          <title>Restasis</title>
          <description>Cyclosporine</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
            <count group_id="B2" value="37"/>
            <count group_id="B3" value="75"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="63"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.06" spread="13.68"/>
                    <measurement group_id="B2" value="51.21" spread="14.44"/>
                    <measurement group_id="B3" value="52.64" spread="14.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression of Dry Eye Severity</title>
        <description>Dry eye is one of the major symptoms of ocular GVHD in bone-marrow transplant recipients, worsening of dry eye symptoms may be indicative of worsening ocular GVHD conditions.</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Lotemax</title>
            <description>Loteprednol Etabonate 0.5%</description>
          </group>
          <group group_id="O2">
            <title>Restasis</title>
            <description>Cyclosporine</description>
          </group>
        </group_list>
        <measure>
          <title>Progression of Dry Eye Severity</title>
          <description>Dry eye is one of the major symptoms of ocular GVHD in bone-marrow transplant recipients, worsening of dry eye symptoms may be indicative of worsening ocular GVHD conditions.</description>
          <units>patients with increased dry eye severity</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Lotemax</title>
          <description>Loteprednol Etabonate 0.5%&#xD;
Lotemax</description>
        </group>
        <group group_id="E2">
          <title>Restasis</title>
          <description>Cyclosporine&#xD;
Restasis</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>death</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="38"/>
                <counts group_id="E2" events="17" subjects_affected="17" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="38"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>severe Dry eye</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="38"/>
                <counts group_id="E2" events="12" subjects_affected="12" subjects_at_risk="37"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr Shahzad Mian</name_or_title>
      <organization>University of Michigan</organization>
      <phone>734-647-8397</phone>
      <email>smian@med.umich.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01695668
org study id: Lotemax_00045815
nct id: NCT01695668
lead sponsor: 
collaborator: 
has dmc: No
The purpose of this research is to:

        1. Evaluate the safety and efficacy of a steroid eye drop (Lotemax) in patients who have
           been diagnosed with graft-versus-host disease (GVHD), which is a complication that may
           occur after bone marrow transplant where the newly transplanted material attacks the
           patient's body and may cause eye dryness.

        2. Assess the safety and efficacy of Lotemax in decreasing the eye's reaction to the
           process in GVHD before the patient undergoes bone marrow transplant.

        3. Compare how well Lotemax works in decreasing the process in GVHD with an
           immunosuppressive eye drop (Restasis), which has been commonly used in the treatment of
           this condition.
Allogeneic bone marrow or peripheral stem cell transplantation result in Graft-versus-Host
      disease. Ocular symptoms may be the first presentation of GVHD and may be seen in the absence
      of systemic manifestations. GVHD is categorized into acute and chronic forms as defined by
      100 days after the transplant. Acute GVHD is characterized by dermatitis, hepatitis, and
      enteritis. Chronic GVHD involves the skin, mouth, liver, gastrointestinal tract, lungs, and
      eyes. Ocular GVHD is a common cause of dry eye symptoms in patients who have undergone bone
      marrow transplant (BMT), and can be defined as ocular surface disease in the context of GVHD.
      Dry eyes develop in 76% of acute GVHD patients and between 62.5% and 81.8% of chronic GVHD
      patients. Current treatment for ocular GVHD includes topical cyclosporine 0.05% (Restasis,
      Allergan). Topical loteprednol etabonate 0.5% (Lotemax, Bausch and Lomb) has been shown to be
      safe and efficacious in treatment of inflammatory ocular disorders, but has not been
      prospectively studied in ocular GVHD.

      2. Hypothesis: We anticipate that topical loteprednol etabonate 0.5% will be safe and
      efficacious in treatment of ocular GVHD patients, and would add to the armamentarium of
      therapeutics for this disease. Further, by following the natural progression of the disease
      prior to a patient's Bone Marrow Transplant (BMT), we may elucidate a new standard of care
      for these patients - one that involves referral to an ophthalmologist before ocular GVHD
      symptoms arise.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Progression of Dry Eye Severity
time frame: 1 year
description: Dry eye is one of the major symptoms of ocular GVHD in bone-marrow transplant recipients, worsening of dry eye symptoms may be indicative of worsening ocular GVHD conditions.
arm group label: Lotemax
arm group type: Experimental
description: Loteprednol Etabonate 0.5%
arm group label: Restasis
arm group type: Active Comparator
description: Cyclosporine
intervention type: Drug
intervention name: Lotemax
description: Ophthalmic corticosteroid. It decreases inflammation of the eye
arm group label: Lotemax
other name: Loteprednol
intervention type: Drug
intervention name: Restasis
description: Restasis is an immunosuppressive agent. Cyclosporine may reduce inflammation in the eye.
arm group label: Restasis
other name: cyclosporine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Shahzad Mian, MD
role: Principal Investigator
affiliation: University of Michigan
responsible party type: Principal Investigator
investigator affiliation: University of Michigan
investigator full name: Shahzad Mian
investigator title: Terry J. Bergstrom Professor for Resident Education, Associate Professor, Cornea and External Disease
mesh term: Dry Eye Syndromes
mesh term: Graft vs Host Disease
mesh term: Loteprednol Etabonate
mesh term: Cyclosporine
mesh term: Cyclosporins
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 