<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/NCT02197065</url>
  </required_header>
  <id_info>
    <org_study_id>EPAR4398</org_study_id>
    <secondary_id>UL1TR000457-06</secondary_id>
    <nct_id>NCT02197065</nct_id>
  </id_info>
  <brief_title>Pilot Study of Atorvastatin for Orthopedic Surgery Patients</brief_title>
  <acronym>POST-OP Pilot</acronym>
  <official_title>The Post-Operative Statin for Thromboprophylaxis &amp; Cardiovascular Outcomes Protection (POST-OP) Pilot Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Up to 35% of hip fracture patients have been shown to experience heart injury after surgery,&#xD;
      and as many as 10% have a heart attack or die in the three months after surgery. Hip and knee&#xD;
      arthroplasty patients are also at risk of cardiovascular complications. Patients who have&#xD;
      these complications have higher levels of inflammation postoperatively. Statins (such as&#xD;
      atorvastatin/Lipitor) lower cholesterol and also lessen inflammation. Both of these effects&#xD;
      are important in preventing heart attacks. Statins have been shown to reduce the risk of&#xD;
      heart attacks in non-surgical patients, and to protect from heart attacks in patients having&#xD;
      heart surgery. Whether statins can prevent heart attacks in orthopedic patients is not known.&#xD;
&#xD;
      In this pilot study the investigators will treat 30 orthopedic surgery patients (hip&#xD;
      fracture, hip or knee arthroplasty) with either atorvastatin or placebo (a capsule with no&#xD;
      study drug). Patients will start the study drug prior to surgery and take it for 45 days&#xD;
      after surgery. Neither the doctors nor the patients will know whether they are taking&#xD;
      atorvastatin or placebo. The investigators will look for evidence of inflammation and heart&#xD;
      injury after surgery. The investigators hypothesize that atorvastatin will lessen the degree&#xD;
      of postoperative inflammation found in these patients. In this study, the investigators will&#xD;
      use a very sensitive test of heart injury that can detect problems even when patients have no&#xD;
      symptoms. The investigators hypothesize that this test will demonstrate silent heart injury&#xD;
      in over 50% of the hip fracture patients and over 30% of arthroplasty patients in our study.&#xD;
&#xD;
      The results of this trial will help us to develop a larger study in 1000 hip fracture and&#xD;
      joint replacement patients to determine whether atorvastatin protects orthopedic surgery&#xD;
      patients from heart injury and other complications of surgery.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      -  Thirty statin-naïve patients ≥ 65 years of age admitted to New York Presbyterian&#xD;
           Hospital or Hospital for Special Surgery with an acute hip fracture, or for elective hip&#xD;
           or knee arthroplasty will be randomized in a 1:1 ratio to atorvastatin 40 mg daily or&#xD;
           matching placebo.&#xD;
&#xD;
        -  Atorvastatin will be initiated at least 4 hours prior to hip fracture surgery, or 4 days&#xD;
           prior to arthroplasty, and will be continued until postoperative day (POD) 45.&#xD;
&#xD;
        -  Patients will be assessed daily in the hospital for adverse events.&#xD;
&#xD;
        -  Patients will be contacted by telephone weekly for four weeks after surgery and again on&#xD;
           POD 45 and POD 90.&#xD;
&#xD;
        -  Patients will mail back study medication bottles on POD 45 for pill counts to assess&#xD;
           compliance.&#xD;
&#xD;
        -  High sensitivity cardiac troponin I (hs-cTnI) will be measured pre-operatively (prior to&#xD;
           atorvastatin therapy) and on POD 2.&#xD;
&#xD;
        -  High sensitivity C-reactive protein (hs-CRP), and a panel of cytokines (IL-1β, IL-2,&#xD;
           IL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor&#xD;
           (TNF)-α, interferon (IFN)-γ, and soluble (s)CD-40L) will be measured preoperatively and&#xD;
           on POD 2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2014</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I</measure>
    <time_frame>change from preoperative to postoperative day 2</time_frame>
    <description>The percentage of orthopedic patients with a ≥ 10 pg/mL rise in high-sensitivity cardiac troponin I (hs-cTnI) from baseline pre-operatively to post-operative day (POD)2</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)</measure>
    <time_frame>Change from preoperative to post-operative day 2</time_frame>
    <description>The change in the level of hs-CRP from baseline to POD2 in 20 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peri-operative Rise in Interleukin-6 (IL-6) Levels</measure>
    <time_frame>Change from preoperative to postoperative day 2</time_frame>
    <description>The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Hip Fracture</condition>
  <condition>Myocardial Ischemia</condition>
  <condition>Inflammation</condition>
  <arm_group>
    <arm_group_label>Atorvastatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atorvastatin</intervention_name>
    <description>Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45</description>
    <arm_group_label>Atorvastatin</arm_group_label>
    <other_name>Lipitor</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Sugar pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Hip fracture or elective hip or knee arthroplasty&#xD;
&#xD;
          -  Age 65 years or older&#xD;
&#xD;
          -  Life expectancy &gt; 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pathological hip fracture due to cancer&#xD;
&#xD;
          -  Currently taking a statin, or took a statin within the last 30 days&#xD;
&#xD;
          -  Previous statin intolerance&#xD;
&#xD;
          -  Acute myocardial infarction or unstable angina&#xD;
&#xD;
          -  History of myocardial infarction, acute coronary syndrome, angina, coronary/arterial&#xD;
             re-vascularization&#xD;
&#xD;
          -  Hip fracture patients with peripheral arterial disease&#xD;
&#xD;
          -  Hip fracture patients with history of stroke or transient ischemic attack.&#xD;
&#xD;
          -  Muscle disorder&#xD;
&#xD;
          -  Serious liver disease or alanine aminotransferase &gt; 3x upper limit of normal&#xD;
&#xD;
          -  Serious renal disease (creatinine clearance &lt;30cc/min)&#xD;
&#xD;
          -  Treatment with HIV protease inhibitor or Hepatitis C protease inhibitor&#xD;
&#xD;
          -  Treatment with erythromycin, clarithromycin, niacin or azole antifungal agent&#xD;
&#xD;
          -  Pregnant, planning to become pregnant, or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anne R Bass, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York Presbyterian Hospital (Cornell)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>July 21, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <results_first_submitted>April 20, 2017</results_first_submitted>
  <results_first_submitted_qc>June 2, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">July 2, 2017</results_first_posted>
  <last_update_submitted>June 2, 2017</last_update_submitted>
  <last_update_submitted_qc>June 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hip fracture</keyword>
  <keyword>myocardial ischemia</keyword>
  <keyword>statin</keyword>
  <keyword>surgery</keyword>
  <keyword>troponin</keyword>
  <keyword>complication</keyword>
  <keyword>arthroplasty</keyword>
  <keyword>hip</keyword>
  <keyword>knee</keyword>
  <keyword>orthopedic</keyword>
  <keyword>atorvastatin</keyword>
  <keyword>cardiovascular</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Myocardial Ischemia</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Ischemia</mesh_term>
    <mesh_term>Hip Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atorvastatin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Atorvastatin</title>
          <description>Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Atorvastatin: Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45</description>
        </group>
        <group group_id="P2">
          <title>Sugar Pill</title>
          <description>Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Atorvastatin</title>
          <description>Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Atorvastatin: Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45</description>
        </group>
        <group group_id="B2">
          <title>Sugar Pill</title>
          <description>Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Placebo</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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" lower_limit="67" upper_limit="76"/>
                    <measurement group_id="B2" value="75" lower_limit="72" upper_limit="84"/>
                    <measurement group_id="B3" value="73" lower_limit="70" upper_limit="82"/>
                  </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="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </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>
          <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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </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>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Orthopedic procedure</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Knee arthroplasty</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hip arthroplasty</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hip fracture repair</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I</title>
        <description>The percentage of orthopedic patients with a ≥ 10 pg/mL rise in high-sensitivity cardiac troponin I (hs-cTnI) from baseline pre-operatively to post-operative day (POD)2</description>
        <time_frame>change from preoperative to postoperative day 2</time_frame>
        <population>20 orthopedic surgery patients.</population>
        <group_list>
          <group group_id="O1">
            <title>All Patients</title>
            <description>All patients in the study</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I</title>
          <description>The percentage of orthopedic patients with a ≥ 10 pg/mL rise in high-sensitivity cardiac troponin I (hs-cTnI) from baseline pre-operatively to post-operative day (POD)2</description>
          <population>20 orthopedic surgery patients.</population>
          <units>percentage of patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>This was a pilot feasibility study and we were only powered to determine the frequency of troponin elevation in the entire study population, not to compare the frequency of a rise in troponin in the two study arms. Thus Aim 1 applies to the entire study cohort.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Proportion</param_type>
            <param_value>0.2</param_value>
            <ci_n_sides>1-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)</title>
        <description>The change in the level of hs-CRP from baseline to POD2 in 20 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
        <time_frame>Change from preoperative to post-operative day 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Atorvastatin: Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)</title>
          <description>The change in the level of hs-CRP from baseline to POD2 in 20 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
          <units>mg/L</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.95" lower_limit="63.8" upper_limit="151.4"/>
                    <measurement group_id="O2" value="85.95" lower_limit="52.85" upper_limit="124.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.58</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>13</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peri-operative Rise in Interleukin-6 (IL-6) Levels</title>
        <description>The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
        <time_frame>Change from preoperative to postoperative day 2</time_frame>
        <population>16 arthroplasty patients</population>
        <group_list>
          <group group_id="O1">
            <title>Atorvastatin</title>
            <description>Atorvastatin 40mg daily starting 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.</description>
          </group>
          <group group_id="O2">
            <title>Sugar Pill</title>
            <description>Sugar pill (placebo) daily starting 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.</description>
          </group>
        </group_list>
        <measure>
          <title>Peri-operative Rise in Interleukin-6 (IL-6) Levels</title>
          <description>The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.</description>
          <population>16 arthroplasty patients</population>
          <units>pg/mL</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.28" lower_limit="0.09" upper_limit="1.58"/>
                    <measurement group_id="O2" value="0.98" lower_limit="0.53" upper_limit="1.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1.00</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
            <param_type>Median Difference (Final Values)</param_type>
            <param_value>0.3</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>90 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Atorvastatin</title>
          <description>Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Atorvastatin: Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45</description>
        </group>
        <group group_id="E2">
          <title>Sugar Pill</title>
          <description>Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.&#xD;
Placebo</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>fluid overload</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>bacteremia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>alcohol withdrawal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>deep vein thrombosis</sub_title>
                <description>calf vein</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>delirium</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>pruritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </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>
    <limitations_and_caveats>Small sample size: recruitment was made difficult by comorbidities in hip fracture patients that limited participation, the reluctance of arthroplasty patients to enroll in an interventional trial, and statin use in 40% of the target population.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Anne R. Bass, MD</name_or_title>
      <organization>Hospital for Special Surgery</organization>
      <phone>212-774-7043</phone>
      <email>bassa@hss.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/NCT02197065
org study id: EPAR4398
secondary id: UL1TR000457-06
nct id: NCT02197065
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Up to 35% of hip fracture patients have been shown to experience heart injury after surgery,
      and as many as 10% have a heart attack or die in the three months after surgery. Hip and knee
      arthroplasty patients are also at risk of cardiovascular complications. Patients who have
      these complications have higher levels of inflammation postoperatively. Statins (such as
      atorvastatin/Lipitor) lower cholesterol and also lessen inflammation. Both of these effects
      are important in preventing heart attacks. Statins have been shown to reduce the risk of
      heart attacks in non-surgical patients, and to protect from heart attacks in patients having
      heart surgery. Whether statins can prevent heart attacks in orthopedic patients is not known.

      In this pilot study the investigators will treat 30 orthopedic surgery patients (hip
      fracture, hip or knee arthroplasty) with either atorvastatin or placebo (a capsule with no
      study drug). Patients will start the study drug prior to surgery and take it for 45 days
      after surgery. Neither the doctors nor the patients will know whether they are taking
      atorvastatin or placebo. The investigators will look for evidence of inflammation and heart
      injury after surgery. The investigators hypothesize that atorvastatin will lessen the degree
      of postoperative inflammation found in these patients. In this study, the investigators will
      use a very sensitive test of heart injury that can detect problems even when patients have no
      symptoms. The investigators hypothesize that this test will demonstrate silent heart injury
      in over 50% of the hip fracture patients and over 30% of arthroplasty patients in our study.

      The results of this trial will help us to develop a larger study in 1000 hip fracture and
      joint replacement patients to determine whether atorvastatin protects orthopedic surgery
      patients from heart injury and other complications of surgery.
-  Thirty statin-naïve patients ≥ 65 years of age admitted to New York Presbyterian
           Hospital or Hospital for Special Surgery with an acute hip fracture, or for elective hip
           or knee arthroplasty will be randomized in a 1:1 ratio to atorvastatin 40 mg daily or
           matching placebo.

        -  Atorvastatin will be initiated at least 4 hours prior to hip fracture surgery, or 4 days
           prior to arthroplasty, and will be continued until postoperative day (POD) 45.

        -  Patients will be assessed daily in the hospital for adverse events.

        -  Patients will be contacted by telephone weekly for four weeks after surgery and again on
           POD 45 and POD 90.

        -  Patients will mail back study medication bottles on POD 45 for pill counts to assess
           compliance.

        -  High sensitivity cardiac troponin I (hs-cTnI) will be measured pre-operatively (prior to
           atorvastatin therapy) and on POD 2.

        -  High sensitivity C-reactive protein (hs-CRP), and a panel of cytokines (IL-1β, IL-2,
           IL-2r, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, tumor necrosis factor
           (TNF)-α, interferon (IFN)-γ, and soluble (s)CD-40L) will be measured preoperatively and
           on POD 2.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of All Enrolled Patients With a Peri-operative Rise in High-sensitivity Cardiac Troponin I
time frame: change from preoperative to postoperative day 2
description: The percentage of orthopedic patients with a ≥ 10 pg/mL rise in high-sensitivity cardiac troponin I (hs-cTnI) from baseline pre-operatively to post-operative day (POD)2
measure: Peri-operative Rise in High Sensitivity C-reactive Protein (Hs-CRP)
time frame: Change from preoperative to post-operative day 2
description: The change in the level of hs-CRP from baseline to POD2 in 20 orthopedic patients randomized (1:1) to atorvastatin 40mg versus placebo.
measure: Peri-operative Rise in Interleukin-6 (IL-6) Levels
time frame: Change from preoperative to postoperative day 2
description: The change in the level of IL-6 from baseline to POD2 in 16 arthroplasty patients randomized (1:1) to atorvastatin 40mg versus placebo.
arm group label: Atorvastatin
arm group type: Experimental
description: Atorvastatin 40mg daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.
arm group label: Sugar pill
arm group type: Placebo Comparator
description: Sugar pill (placebo) daily starting at least 4 hours prior to hip fracture surgery, or 4 days prior to hip or knee arthroplasty, and continued until postoperative day 45.
intervention type: Drug
intervention name: Atorvastatin
description: Atorvastatin or placebo will be started at least 4 hours prior to surgery, and continued nightly until postoperative day 45
arm group label: Atorvastatin
other name: Lipitor
intervention type: Drug
intervention name: Placebo
arm group label: Sugar pill
criteria: 
gender: All
minimum age: 65 Years
maximum age: 99 Years
healthy volunteers: No
last name: Anne R Bass, MD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Myocardial Ischemia
mesh term: Coronary Artery Disease
mesh term: Inflammation
mesh term: Ischemia
mesh term: Hip Fractures
mesh term: Atorvastatin
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Small sample size: recruitment was made difficult by comorbidities in hip fracture patients that limited participation, the reluctance of arthroplasty patients to enroll in an interventional trial, and statin use in 40% of the target population.
point of contact: 