<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/NCT01705587</url>
  </required_header>
  <id_info>
    <org_study_id>PRO12040560 (FiX-IT)</org_study_id>
    <nct_id>NCT01705587</nct_id>
  </id_info>
  <brief_title>Fracture (FX) Improvement With Teriparatide: FiX-IT Study</brief_title>
  <acronym>FiX-IT</acronym>
  <official_title>Fracture (FX) Improvement With Teriparatide: FiX-IT Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Susan L. Greenspan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Pittsburgh</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This open label comparison study examines the hypothesis that teriparatide given immediately&#xD;
      following repair of an atypical subtrochanteric or diaphyseal femoral shaft fracture will&#xD;
      enhance healing and improve bone mineral density compared to delayed treatment (after six&#xD;
      months) with teriparatide or no treatment with teriparatide (patients who refuse therapy or&#xD;
      for whom teriparatide is contraindicated). Patients with up-front teriparatide in addition&#xD;
      will have greater quality of life measures and less pain compared to those with delayed or no&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to 24 postmenopausal women with osteoporosis who have been on bisphosphonate therapy for&#xD;
      one year or more at any point prior to fracture and have sustained an atypical&#xD;
      subtrochanteric or diaphyseal fracture will be enrolled. Subjects randomized to the two&#xD;
      intervention arms will self-administer a daily SQ injection of the study medication for 12&#xD;
      months. The primary objective is to demonstrate greater radiologic evidence of healing at 10&#xD;
      weeks in patients on immediate teriparatide compared to those on delayed teriparatide who&#xD;
      receive therapy six months after fracture. Secondary end points include (1) radiologic&#xD;
      healing at 2, 6, 24, and 46 weeks; (2) increased bone density at 6 and 12 months as assessed&#xD;
      by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, and femoral neck; (3)&#xD;
      quality of life improvements at 10 weeks and 6 months as assessed by quality of life&#xD;
      questionnaire and pain score; and (4) differences in biochemical markers of bone turnover in&#xD;
      patient with upfront therapy compared to patients with delayed therapy and patients who&#xD;
      refuse therapy or for whom teriparatide is contraindicated.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2012</start_date>
  <completion_date type="Actual">September 2016</completion_date>
  <primary_completion_date type="Actual">September 2016</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>Radiologic Evidence of Bone Healing</measure>
    <time_frame>6, 12 months of treatment</time_frame>
    <description>The radiologic indices of fracture healing included (1) cortical continuity on two of four cortices, (2) persistence of alignment, (3) decreased conspicuity of fracture line, and (4) increased callus formation. For each of these indices, healing was graded on a scale of 1 to 4 with 1 = no change (less than 25%), 2 = minimum healing (25-50%), 3 = moderate healing (50-75%), and 4 = complete healing (greater than 75%). A composite score was calculated by summing the subscale scores for the 4 indices. Composite score scale ranged from 4 to 16 with higher scores indicating more complete healing. The primary grading was performed by a radiologist with expertise in musculoskeletal radiology, then independently repeated by a second radiologist, both of whom were blinded to the study allocation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Radiologic Evidence of Healing</measure>
    <time_frame>at 10 weeks for immediate teriparatide group</time_frame>
    <description>Number of participants with persistence of alignment as determined by a radiologist.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Radiologic Healing</measure>
    <time_frame>at 2, 6, 24, and 48 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Increased Bone Density</measure>
    <time_frame>at 6 and 12 months</time_frame>
    <description>Percent change in Bone Mineral Density (BMD) as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, distal 1/3 radius, and femoral neck</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Improvements</measure>
    <time_frame>at 12 months</time_frame>
    <description>Assessed by quality of life questionnaire (SF-36). There are 8 subscales each ranging from 0-100 with higher scores indicating better quality of life.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in Biochemical Markers of Bone Turnover</measure>
    <time_frame>intervals over 12-18 months depending on treatment group</time_frame>
    <description>upfront therapy group compared to delayed therapy group and no therapy group</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Osteoporosis</condition>
  <condition>Atypical Femoral Fracture</condition>
  <arm_group>
    <arm_group_label>Immediate teriparatide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label teriparatide given immediately following surgical repair of fracture</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Delayed teriparatide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open label teriparatide given six months following surgical repair of fracture</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>teriparatide</intervention_name>
    <description>20 microgram once-daily subcutaneous injection</description>
    <arm_group_label>Delayed teriparatide</arm_group_label>
    <arm_group_label>Immediate teriparatide</arm_group_label>
    <other_name>Forteo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  postmenopausal women&#xD;
&#xD;
          -  with osteoporosis who have been on bisphosphonate therapy for one year or more (all&#xD;
             bisphosphonates will be included such as alendronate, risdedronate, ibandronate, or&#xD;
             zoledronic acid).&#xD;
&#xD;
          -  Patients will also be included if they are on glucocorticoids or other medications&#xD;
             known to affect bone mineral metabolism as these are often found in patients with&#xD;
             these types of fractures.&#xD;
&#xD;
          -  sustain an atypical subtrochanteric or diaphyseal femoral shaft fracture as defined by&#xD;
             the the 2010 ASBMR task force. An atypical fracture must include all of the following:&#xD;
             (1) a location in the femur distal to lesser trochanter; (2) no trauma or minimal&#xD;
             trauma as a fall; (3) transverse or short oblique configuration; (4) noncomminuted;&#xD;
             and (5) complete fracture extends through both cortices and may be associated with a&#xD;
             medial spike; incomplete fractures involve only the lateral cortex. Patients who have&#xD;
             an incomplete fracture can be included if they fall into the 2010 ASBMR task force&#xD;
             definition.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  men&#xD;
&#xD;
          -  children&#xD;
&#xD;
          -  those who have had radiation therapy&#xD;
&#xD;
          -  Paget's disease&#xD;
&#xD;
          -  treatment with teriparatide for two year in the past&#xD;
&#xD;
          -  metastatic bone disease&#xD;
&#xD;
          -  active cancer&#xD;
&#xD;
          -  hypercalcemia&#xD;
&#xD;
          -  hyperparathyroidism&#xD;
&#xD;
          -  metabolic disease other than osteoporosis&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Susan L. Greenspan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Pittsburgh</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh, Osteoporosis Prevention &amp; Treatment Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 11, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 12, 2012</study_first_posted>
  <results_first_submitted>August 30, 2017</results_first_submitted>
  <results_first_submitted_qc>November 6, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 12, 2017</results_first_posted>
  <last_update_submitted>November 6, 2017</last_update_submitted>
  <last_update_submitted_qc>November 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 12, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
    <investigator_full_name>Susan L. Greenspan</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>osteoporosis</keyword>
  <keyword>atypical femoral fractures</keyword>
  <keyword>prior bisphosphonate treatment</keyword>
  <keyword>postmenopausal women</keyword>
  <keyword>bone loss</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoporosis</mesh_term>
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Femoral Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Teriparatide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Immediate Teriparatide</title>
          <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
        </group>
        <group group_id="P2">
          <title>Delayed Teriparatide</title>
          <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Immediate Teriparatide</title>
          <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
        </group>
        <group group_id="B2">
          <title>Delayed Teriparatide</title>
          <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</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="7"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="13"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="78.0" spread="8.660"/>
                    <measurement group_id="B2" value="69.8" spread="8.085"/>
                    <measurement group_id="B3" value="74.2" spread="9.094"/>
                  </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="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</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>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Radiologic Evidence of Bone Healing</title>
        <description>The radiologic indices of fracture healing included (1) cortical continuity on two of four cortices, (2) persistence of alignment, (3) decreased conspicuity of fracture line, and (4) increased callus formation. For each of these indices, healing was graded on a scale of 1 to 4 with 1 = no change (less than 25%), 2 = minimum healing (25-50%), 3 = moderate healing (50-75%), and 4 = complete healing (greater than 75%). A composite score was calculated by summing the subscale scores for the 4 indices. Composite score scale ranged from 4 to 16 with higher scores indicating more complete healing. The primary grading was performed by a radiologist with expertise in musculoskeletal radiology, then independently repeated by a second radiologist, both of whom were blinded to the study allocation.</description>
        <time_frame>6, 12 months of treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Radiologic Evidence of Bone Healing</title>
          <description>The radiologic indices of fracture healing included (1) cortical continuity on two of four cortices, (2) persistence of alignment, (3) decreased conspicuity of fracture line, and (4) increased callus formation. For each of these indices, healing was graded on a scale of 1 to 4 with 1 = no change (less than 25%), 2 = minimum healing (25-50%), 3 = moderate healing (50-75%), and 4 = complete healing (greater than 75%). A composite score was calculated by summing the subscale scores for the 4 indices. Composite score scale ranged from 4 to 16 with higher scores indicating more complete healing. The primary grading was performed by a radiologist with expertise in musculoskeletal radiology, then independently repeated by a second radiologist, both of whom were blinded to the study allocation.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>6 mo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" spread="0.6"/>
                    <measurement group_id="O2" value="11.2" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 mo</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4" spread="0.4"/>
                    <measurement group_id="O2" value="13.2" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Radiologic Evidence of Healing</title>
        <description>Number of participants with persistence of alignment as determined by a radiologist.</description>
        <time_frame>at 10 weeks for immediate teriparatide group</time_frame>
        <population>Based on orthopedic surgeons' assessment, x-rays were not deemed necessary in over 30% of patients at week 10. Results presented are for those who had x-rays at 10 weeks to assess persistence of alignment for safety purposes.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Radiologic Evidence of Healing</title>
          <description>Number of participants with persistence of alignment as determined by a radiologist.</description>
          <population>Based on orthopedic surgeons' assessment, x-rays were not deemed necessary in over 30% of patients at week 10. Results presented are for those who had x-rays at 10 weeks to assess persistence of alignment for safety purposes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiologic Healing</title>
        <time_frame>at 2, 6, 24, and 48 weeks</time_frame>
        <population>Data not collected at 2 and 6 weeks. Twenty-Four week (6 months) data is presented in 6 month outcomes, and 48 week (12 months) data as 12 month outcomes (See primary outcomes section above).</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Radiologic Healing</title>
          <population>Data not collected at 2 and 6 weeks. Twenty-Four week (6 months) data is presented in 6 month outcomes, and 48 week (12 months) data as 12 month outcomes (See primary outcomes section above).</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Increased Bone Density</title>
        <description>Percent change in Bone Mineral Density (BMD) as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, distal 1/3 radius, and femoral neck</description>
        <time_frame>at 6 and 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Increased Bone Density</title>
          <description>Percent change in Bone Mineral Density (BMD) as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, distal 1/3 radius, and femoral neck</description>
          <units>percentage change in BMD</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Spine-PA (6 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.1" spread="1.5"/>
                    <measurement group_id="O2" value="-0.6" spread="1.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spine-PA (12 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" spread="2.0"/>
                    <measurement group_id="O2" value="5.4" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Hip (6 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="1.5"/>
                    <measurement group_id="O2" value="-0.8" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Hip (12 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.8"/>
                    <measurement group_id="O2" value="1.5" spread="2.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Femoral Neck (6 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" spread="2.1"/>
                    <measurement group_id="O2" value="-2.7" spread="1.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Femoral Neck (12 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="3.0"/>
                    <measurement group_id="O2" value="-1.9" spread="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Distal 1/3 Radius (6 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="1.9"/>
                    <measurement group_id="O2" value="-0.7" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Distal 1/3 Radius (12 months)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="1.7"/>
                    <measurement group_id="O2" value="-6.1" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Improvements</title>
        <description>Assessed by quality of life questionnaire (SF-36). There are 8 subscales each ranging from 0-100 with higher scores indicating better quality of life.</description>
        <time_frame>at 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Improvements</title>
          <description>Assessed by quality of life questionnaire (SF-36). There are 8 subscales each ranging from 0-100 with higher scores indicating better quality of life.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.3" spread="6.5"/>
                    <measurement group_id="O2" value="65.0" spread="20.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Physical health limitations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.2" spread="9.1"/>
                    <measurement group_id="O2" value="68.8" spread="21.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional health limitations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.0" spread="9.1"/>
                    <measurement group_id="O2" value="72.9" spread="19.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Energy/Fatigue</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.5" spread="7.4"/>
                    <measurement group_id="O2" value="59.4" spread="15.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Emotional well-being</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="80.7" spread="4.1"/>
                    <measurement group_id="O2" value="70.0" spread="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Social functioning</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.9" spread="4.6"/>
                    <measurement group_id="O2" value="65.6" spread="23.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.9" spread="9.7"/>
                    <measurement group_id="O2" value="59.4" spread="21.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General health</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.1" spread="6.2"/>
                    <measurement group_id="O2" value="67.2" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Difference in Biochemical Markers of Bone Turnover</title>
        <description>upfront therapy group compared to delayed therapy group and no therapy group</description>
        <time_frame>intervals over 12-18 months depending on treatment group</time_frame>
        <population>Funding unavailable for sample analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Immediate Teriparatide</title>
            <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
          <group group_id="O2">
            <title>Delayed Teriparatide</title>
            <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
          </group>
        </group_list>
        <measure>
          <title>Difference in Biochemical Markers of Bone Turnover</title>
          <description>upfront therapy group compared to delayed therapy group and no therapy group</description>
          <population>Funding unavailable for sample analysis.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Immediate Teriparatide</title>
          <description>Open label teriparatide given immediately following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
        </group>
        <group group_id="E2">
          <title>Delayed Teriparatide</title>
          <description>Open label teriparatide given six months following surgical repair of fracture&#xD;
teriparatide: 20 microgram once-daily subcutaneous injection</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal coagulation profile</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hematoma</sub_title>
                <description>Hospitalized for incision and drainage of right hip hematoma at femoral surgical site</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Developed cellulitis at surgical site following repair of femur fracture</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Ewings Sarcoma</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Discovered prior to initiation of treatment with teritparatide</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>elective back surgery</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="7"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>myringotomy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>macular degeneration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>gingivitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>allergic rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>varicella zoster</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>arthralgias</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>thigh pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>aphasia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>cataract removal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>periodontal gum surgery</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>cardiac catheterization</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>deep vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>coronary artery disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </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>Susan Greenspan, MD</name_or_title>
      <organization>University of Pittsburgh</organization>
      <phone>412-692-2477</phone>
      <email>greenspn@pitt.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/NCT01705587
org study id: PRO12040560 (FiX-IT)
nct id: NCT01705587
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
This open label comparison study examines the hypothesis that teriparatide given immediately
      following repair of an atypical subtrochanteric or diaphyseal femoral shaft fracture will
      enhance healing and improve bone mineral density compared to delayed treatment (after six
      months) with teriparatide or no treatment with teriparatide (patients who refuse therapy or
      for whom teriparatide is contraindicated). Patients with up-front teriparatide in addition
      will have greater quality of life measures and less pain compared to those with delayed or no
      therapy.
Up to 24 postmenopausal women with osteoporosis who have been on bisphosphonate therapy for
      one year or more at any point prior to fracture and have sustained an atypical
      subtrochanteric or diaphyseal fracture will be enrolled. Subjects randomized to the two
      intervention arms will self-administer a daily SQ injection of the study medication for 12
      months. The primary objective is to demonstrate greater radiologic evidence of healing at 10
      weeks in patients on immediate teriparatide compared to those on delayed teriparatide who
      receive therapy six months after fracture. Secondary end points include (1) radiologic
      healing at 2, 6, 24, and 46 weeks; (2) increased bone density at 6 and 12 months as assessed
      by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, and femoral neck; (3)
      quality of life improvements at 10 weeks and 6 months as assessed by quality of life
      questionnaire and pain score; and (4) differences in biochemical markers of bone turnover in
      patient with upfront therapy compared to patients with delayed therapy and patients who
      refuse therapy or for whom teriparatide is contraindicated.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Radiologic Evidence of Bone Healing
time frame: 6, 12 months of treatment
description: The radiologic indices of fracture healing included (1) cortical continuity on two of four cortices, (2) persistence of alignment, (3) decreased conspicuity of fracture line, and (4) increased callus formation. For each of these indices, healing was graded on a scale of 1 to 4 with 1 = no change (less than 25%), 2 = minimum healing (25-50%), 3 = moderate healing (50-75%), and 4 = complete healing (greater than 75%). A composite score was calculated by summing the subscale scores for the 4 indices. Composite score scale ranged from 4 to 16 with higher scores indicating more complete healing. The primary grading was performed by a radiologist with expertise in musculoskeletal radiology, then independently repeated by a second radiologist, both of whom were blinded to the study allocation.
measure: Radiologic Evidence of Healing
time frame: at 10 weeks for immediate teriparatide group
description: Number of participants with persistence of alignment as determined by a radiologist.
measure: Radiologic Healing
time frame: at 2, 6, 24, and 48 weeks
measure: Increased Bone Density
time frame: at 6 and 12 months
description: Percent change in Bone Mineral Density (BMD) as assessed by dual x-ray absorptiometry (DXA) at the spine, contralateral hip, distal 1/3 radius, and femoral neck
measure: Quality of Life Improvements
time frame: at 12 months
description: Assessed by quality of life questionnaire (SF-36). There are 8 subscales each ranging from 0-100 with higher scores indicating better quality of life.
measure: Difference in Biochemical Markers of Bone Turnover
time frame: intervals over 12-18 months depending on treatment group
description: upfront therapy group compared to delayed therapy group and no therapy group
arm group label: Immediate teriparatide
arm group type: Experimental
description: Open label teriparatide given immediately following surgical repair of fracture
arm group label: Delayed teriparatide
arm group type: Experimental
description: Open label teriparatide given six months following surgical repair of fracture
intervention type: Drug
intervention name: teriparatide
description: 20 microgram once-daily subcutaneous injection
arm group label: Delayed teriparatide
arm group label: Immediate teriparatide
other name: Forteo
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Susan L. Greenspan, MD
role: Principal Investigator
affiliation: University of Pittsburgh
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Pittsburgh
investigator full name: Susan L. Greenspan
investigator title: Professor of Medicine
mesh term: Osteoporosis
mesh term: Fractures, Bone
mesh term: Femoral Fractures
mesh term: Teriparatide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 