<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/NCT02203071</url>
  </required_header>
  <id_info>
    <org_study_id>1211220</org_study_id>
    <nct_id>NCT02203071</nct_id>
  </id_info>
  <brief_title>Comparison of BioCartilage Versus Marrow Stimulating Procedure for Cartilage Defects of the Knee</brief_title>
  <official_title>Comparison of BioCartilage Versus Marrow Stimulating Procedure for Cartilage Defects of the Knee</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Missouri-Columbia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Arthrex, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Missouri-Columbia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Subjects will be selected among the investigators' patient population who are already&#xD;
      scheduled to receive a marrow stimulating procedure (MSP), with or without the addition of&#xD;
      BioCartilage.&#xD;
&#xD;
      During the surgical operation for MSP, a portion of the patient's blood is taken out and used&#xD;
      to form a patch to cover a cartilage defect of the knee. Currently it is considered standard&#xD;
      of care to either form the patch using only a portion of the patient's blood, or form the&#xD;
      patch using a portion of the patient's blood combined with an FDA-approved augmentation such&#xD;
      as BioCartilage.&#xD;
&#xD;
      This study will collect outcomes data and MRI for patients that are undergoing MSP with and&#xD;
      without BioCartilage augmentation, then compare the data between those who received&#xD;
      BioCartilage and those who did not.&#xD;
&#xD;
      The primary endpoint is to determine whether subjects receiving a marrow stimulating&#xD;
      procedure (MSP) augmented with BioCartilage have improved outcomes (measured using quality of&#xD;
      life indicators, functional outcomes, and MRI) compared to subjects who receive MSP without&#xD;
      the use of BioCartilage.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Recent developments in the treatment of articular cartilage defects have resulted in several&#xD;
      techniques that involve the stimulation of native cellular components for the purpose of&#xD;
      differentiation and proliferation in the cartilage defect. Techniques of interest for this&#xD;
      study are the use of microfracture combined with platelet rich plasma (PRP), and a recently&#xD;
      developed augmentation of the microfracture procedure-BioCartilage.&#xD;
&#xD;
      The microfracture procedure is performed with PowerPick. During the procedure, a patient with&#xD;
      focal cartilage defect undergoes arthroscopic debridement of the defect before microfracture&#xD;
      is used to create holes in the subchondral plate in order to provide access to mesenchymal&#xD;
      stem cells (MSCs). To complete this marrow stimulating procedure (MSP), the microfractured&#xD;
      region is filled with PRP harvested intraoperatively from the patient. A fibrin glue is then&#xD;
      used to cover the defect and hold the PRP repair in place.&#xD;
&#xD;
      This basic MSP has been shown to regenerate cartilage tissue and improve joint function.&#xD;
      Microfracture treatments using PRP are &quot;shown to have good to excellent short-term outcomes&#xD;
      in appropriately indicated patients&quot; (Abrams, Mall, Fortier, Roller, &amp; Cole, 2013), however&#xD;
      successful long-term outcomes have not been demonstrated in the literature.&#xD;
&#xD;
      BioCartilage, a novel therapy developed by Arthrex Inc, is implemented as an augmentation of&#xD;
      the basic approach of using microfracture and PRP. All aspects of the procedure, as well as&#xD;
      indications for the procedure, are the same as the basic MSP described above, except the PRP&#xD;
      is combined with BioCartilage powder, which acts as a scaffolding for cellular growth.&#xD;
      BioCartilage is an FDA approved augmentation of microfracture treatment with PRP, and the&#xD;
      powder itself contains no living cells.&#xD;
&#xD;
      Animal models using BioCartilage have provided data that supports the assertion that the&#xD;
      BioCartilage augmentation may improve outcomes for patients who receive it; however there is&#xD;
      currently no published human clinical outcomes data available for using BioCartilage (Abrams&#xD;
      et al., 2013).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2014</start_date>
  <completion_date type="Actual">September 2018</completion_date>
  <primary_completion_date type="Actual">September 2018</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>MRI Repair Tissue Comparison</measure>
    <time_frame>1 year post-operatively</time_frame>
    <description>The primary endpoint is to determine whether subjects receiving a marrow stimulating procedure (MSP) augmented with BioCartilage have improved outcomes (MRI) compared to subjects who receive MSP without the use of BioCartilage. Quantitative (%fill) and qualitative (tissue quality) MRI assessments of repair tissue will be performed by a musculoskeletal (MSK) radiologist who is blinded to treatment group, and compared for differences between treatment groups.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Short Form-12 Health Survey (SF-12)</measure>
    <time_frame>Approximately 2 years</time_frame>
    <description>The 12-item Short Form Survey (SF-12) is a general health questionnaire. The SF-12 was constructed using questions drawn from each of the 8 dimensions of the MOS 36 item Short Form Survey (SF-36). It is designed to have similar performance to the SF-36, while taking less time to complete. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Marx Activity Rating Scale</measure>
    <time_frame>Approximately 2 years</time_frame>
    <description>The Marx Scale consists of four questions concerning four activities or actions: running, cutting, deceleration, and pivoting. The patient or survey respondent is asked to report on the frequency with which they performed the activity in their healthiest state within the past year. The four knee functions are rated on a 5-point scale of frequency and scores are added up to a minimum score of 0 and a maximum of 16 points, with a higher score indicating more frequent participation.</description>
  </other_outcome>
  <other_outcome>
    <measure>Knee Injury and Osteoarthritis Outcomes Score (KOOS)</measure>
    <time_frame>Approximately 2 years</time_frame>
    <description>The Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms. The KOOS is a patient reported joint-specific score, which may be useful for assessing changes in knee pathology over time, with or without treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>International Knee Documentation Committee (IKDC) Subjective Portion</measure>
    <time_frame>Approximately 2 years</time_frame>
    <description>The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things such as pain, stiffness, swelling and giving-way of the knee. Meanwhile, the sports activity subscale focuses on functions like going up and down the stairs, rising from a chair, squatting and jumping. The knee function subscale asks patients one simple question: how is their knee at present versus how was their knee prior to injury?&#xD;
Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of Participants Who Were Able To Return To Return to Work or Sports Activity</measure>
    <time_frame>Approximately 2 years</time_frame>
    <description>This is a two question survey administered to subjects that obtains subjective data &quot;Yes / No&quot; regarding whether the subject has been able to return to work or sports activity since surgery.</description>
  </other_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">25</enrollment>
  <condition>Defect of Articular Cartilage</condition>
  <arm_group>
    <arm_group_label>MSP with BioCartilage</arm_group_label>
    <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MSP without BioCartilage</arm_group_label>
    <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients recruited from Missouri Orthopaedic Institute's patient population.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        I. Inclusion in the study will be considered when all of the following conditions are met:&#xD;
&#xD;
          -  The subject is a candidate for the use of a MSP with microfracture and PRP, with or&#xD;
             without augmentation with BioCartilage, for treatment of a focal defect of the knee&#xD;
             (trochlea or femoral condyle).&#xD;
&#xD;
          -  The subject is 18-years of age or greater&#xD;
&#xD;
          -  The subject is able and willing to consent to participate in the study&#xD;
&#xD;
          -  The subject is expected to be able to safely undergo MRI at the 1-year follow-up visit&#xD;
             (no contraindications present, such as metal implants)&#xD;
&#xD;
          -  Infection or inflammatory arthropathy (such as rheumatoid arthritis) is absent in the&#xD;
             operative knee&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        II. Exclusion from the study will be determined by any one of the following conditions&#xD;
        being met:&#xD;
&#xD;
          -  The subject is undergoing bilateral knee surgery&#xD;
&#xD;
          -  The subject is unwilling, or unable to consent due to psychiatric condition or legal&#xD;
             incompetence&#xD;
&#xD;
          -  The subject is either pregnant, or a prisoner&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>James P Stannard, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Missouri-Columbia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Missouri Orthopaedic Institute</name>
      <address>
        <city>Columbia</city>
        <state>Missouri</state>
        <zip>65212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>June 19, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <results_first_submitted>July 29, 2019</results_first_submitted>
  <results_first_submitted_qc>March 13, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 16, 2020</results_first_posted>
  <last_update_submitted>March 13, 2020</last_update_submitted>
  <last_update_submitted_qc>March 13, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Missouri-Columbia</investigator_affiliation>
    <investigator_full_name>James Stannard</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>sports</keyword>
  <keyword>injury</keyword>
  <keyword>knee</keyword>
  <keyword>pain</keyword>
  <keyword>cartilage</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cartilage Diseases</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 23, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02203071/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>6 Subjects were intra-operative screen failures.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>MSP With BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
        </group>
        <group group_id="P2">
          <title>MSP Without BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>There are six subjects who failed to meet intra-operative criteria for study participation.</population>
      <group_list>
        <group group_id="B1">
          <title>MSP Without BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
        </group>
        <group group_id="B2">
          <title>MSP With BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</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="6"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI (Body Mass Index)</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="6"/>
                    <count group_id="B2" value="13"/>
                    <count group_id="B3" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="31.2" lower_limit="29" upper_limit="34"/>
                    <measurement group_id="B2" value="30.6" lower_limit="22" upper_limit="32"/>
                    <measurement group_id="B3" value="30.8" lower_limit="22" upper_limit="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>MRI Repair Tissue Comparison</title>
        <description>The primary endpoint is to determine whether subjects receiving a marrow stimulating procedure (MSP) augmented with BioCartilage have improved outcomes (MRI) compared to subjects who receive MSP without the use of BioCartilage. Quantitative (%fill) and qualitative (tissue quality) MRI assessments of repair tissue will be performed by a musculoskeletal (MSK) radiologist who is blinded to treatment group, and compared for differences between treatment groups.</description>
        <time_frame>1 year post-operatively</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>MRI Repair Tissue Comparison</title>
          <description>The primary endpoint is to determine whether subjects receiving a marrow stimulating procedure (MSP) augmented with BioCartilage have improved outcomes (MRI) compared to subjects who receive MSP without the use of BioCartilage. Quantitative (%fill) and qualitative (tissue quality) MRI assessments of repair tissue will be performed by a musculoskeletal (MSK) radiologist who is blinded to treatment group, and compared for differences between treatment groups.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</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="13"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&gt;50% fill, isointense</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&lt;50% fill, non-isointense</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </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>0.61</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Short Form-12 Health Survey (SF-12)</title>
        <description>The 12-item Short Form Survey (SF-12) is a general health questionnaire. The SF-12 was constructed using questions drawn from each of the 8 dimensions of the MOS 36 item Short Form Survey (SF-36). It is designed to have similar performance to the SF-36, while taking less time to complete. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.</description>
        <time_frame>Approximately 2 years</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>Short Form-12 Health Survey (SF-12)</title>
          <description>The 12-item Short Form Survey (SF-12) is a general health questionnaire. The SF-12 was constructed using questions drawn from each of the 8 dimensions of the MOS 36 item Short Form Survey (SF-36). It is designed to have similar performance to the SF-36, while taking less time to complete. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Physical and Mental Health Composite Scores (PCS &amp; MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Physical Health Composite Scores</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.4" spread="7"/>
                    <measurement group_id="O2" value="43.4" spread="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Mental Health Composite Scores</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.1" spread="7"/>
                    <measurement group_id="O2" value="59.2" spread="4.3"/>
                  </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>.001</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Marx Activity Rating Scale</title>
        <description>The Marx Scale consists of four questions concerning four activities or actions: running, cutting, deceleration, and pivoting. The patient or survey respondent is asked to report on the frequency with which they performed the activity in their healthiest state within the past year. The four knee functions are rated on a 5-point scale of frequency and scores are added up to a minimum score of 0 and a maximum of 16 points, with a higher score indicating more frequent participation.</description>
        <time_frame>Approximately 2 years</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>Marx Activity Rating Scale</title>
          <description>The Marx Scale consists of four questions concerning four activities or actions: running, cutting, deceleration, and pivoting. The patient or survey respondent is asked to report on the frequency with which they performed the activity in their healthiest state within the past year. The four knee functions are rated on a 5-point scale of frequency and scores are added up to a minimum score of 0 and a maximum of 16 points, with a higher score indicating more frequent participation.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.5" spread="5"/>
                    <measurement group_id="O2" value="3.4" spread="4.2"/>
                  </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>&gt;0.11</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Knee Injury and Osteoarthritis Outcomes Score (KOOS)</title>
        <description>The Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms. The KOOS is a patient reported joint-specific score, which may be useful for assessing changes in knee pathology over time, with or without treatment.</description>
        <time_frame>Approximately 2 years</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>Knee Injury and Osteoarthritis Outcomes Score (KOOS)</title>
          <description>The Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms. The KOOS is a patient reported joint-specific score, which may be useful for assessing changes in knee pathology over time, with or without treatment.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85.9" spread="12"/>
                    <measurement group_id="O2" value="71.6" spread="18"/>
                  </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>&lt;0.007</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>International Knee Documentation Committee (IKDC) Subjective Portion</title>
        <description>The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things such as pain, stiffness, swelling and giving-way of the knee. Meanwhile, the sports activity subscale focuses on functions like going up and down the stairs, rising from a chair, squatting and jumping. The knee function subscale asks patients one simple question: how is their knee at present versus how was their knee prior to injury?&#xD;
Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
        <time_frame>Approximately 2 years</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>International Knee Documentation Committee (IKDC) Subjective Portion</title>
          <description>The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things such as pain, stiffness, swelling and giving-way of the knee. Meanwhile, the sports activity subscale focuses on functions like going up and down the stairs, rising from a chair, squatting and jumping. The knee function subscale asks patients one simple question: how is their knee at present versus how was their knee prior to injury?&#xD;
Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="76.7" spread="13.3"/>
                    <measurement group_id="O2" value="68.9" spread="22.8"/>
                  </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>&lt;0.001</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Participants Who Were Able To Return To Return to Work or Sports Activity</title>
        <description>This is a two question survey administered to subjects that obtains subjective data &quot;Yes / No&quot; regarding whether the subject has been able to return to work or sports activity since surgery.</description>
        <time_frame>Approximately 2 years</time_frame>
        <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</population>
        <group_list>
          <group group_id="O1">
            <title>MSP With BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
          </group>
          <group group_id="O2">
            <title>MSP Without BioCartilage</title>
            <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Were Able To Return To Return to Work or Sports Activity</title>
          <description>This is a two question survey administered to subjects that obtains subjective data &quot;Yes / No&quot; regarding whether the subject has been able to return to work or sports activity since surgery.</description>
          <population>There were 6 screen fails and 10 enrolled subjects who did not complete the study. Fifteen patients who were screened, consented, and enrolled, completed the 2-year study. Five patients who completed the study were assigned to the MSP treatment group and ten were assigned to the BioCartilage treatment group.</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="10"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="4"/>
                  </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</p_value>
            <method>Fisher Exact</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The time period for collection of adverse events is 2 years post intervention.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MSP With BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure with BioCartilage adjunct.</description>
        </group>
        <group group_id="E2">
          <title>MSP Without BioCartilage</title>
          <description>Patients receiving marrow stimulating procedure without BioCartilage.</description>
        </group>
      </group_list>
      <serious_events>
        <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="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Research Project Analyst</name_or_title>
      <organization>University of Missouri</organization>
      <phone>573-882-7583</phone>
      <email>jonesvicki@health.missouri.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/NCT02203071
org study id: 1211220
nct id: NCT02203071
lead sponsor: 
collaborator: 
has dmc: Yes
Subjects will be selected among the investigators' patient population who are already
      scheduled to receive a marrow stimulating procedure (MSP), with or without the addition of
      BioCartilage.

      During the surgical operation for MSP, a portion of the patient's blood is taken out and used
      to form a patch to cover a cartilage defect of the knee. Currently it is considered standard
      of care to either form the patch using only a portion of the patient's blood, or form the
      patch using a portion of the patient's blood combined with an FDA-approved augmentation such
      as BioCartilage.

      This study will collect outcomes data and MRI for patients that are undergoing MSP with and
      without BioCartilage augmentation, then compare the data between those who received
      BioCartilage and those who did not.

      The primary endpoint is to determine whether subjects receiving a marrow stimulating
      procedure (MSP) augmented with BioCartilage have improved outcomes (measured using quality of
      life indicators, functional outcomes, and MRI) compared to subjects who receive MSP without
      the use of BioCartilage.
Recent developments in the treatment of articular cartilage defects have resulted in several
      techniques that involve the stimulation of native cellular components for the purpose of
      differentiation and proliferation in the cartilage defect. Techniques of interest for this
      study are the use of microfracture combined with platelet rich plasma (PRP), and a recently
      developed augmentation of the microfracture procedure-BioCartilage.

      The microfracture procedure is performed with PowerPick. During the procedure, a patient with
      focal cartilage defect undergoes arthroscopic debridement of the defect before microfracture
      is used to create holes in the subchondral plate in order to provide access to mesenchymal
      stem cells (MSCs). To complete this marrow stimulating procedure (MSP), the microfractured
      region is filled with PRP harvested intraoperatively from the patient. A fibrin glue is then
      used to cover the defect and hold the PRP repair in place.

      This basic MSP has been shown to regenerate cartilage tissue and improve joint function.
      Microfracture treatments using PRP are "shown to have good to excellent short-term outcomes
      in appropriately indicated patients" (Abrams, Mall, Fortier, Roller, & Cole, 2013), however
      successful long-term outcomes have not been demonstrated in the literature.

      BioCartilage, a novel therapy developed by Arthrex Inc, is implemented as an augmentation of
      the basic approach of using microfracture and PRP. All aspects of the procedure, as well as
      indications for the procedure, are the same as the basic MSP described above, except the PRP
      is combined with BioCartilage powder, which acts as a scaffolding for cellular growth.
      BioCartilage is an FDA approved augmentation of microfracture treatment with PRP, and the
      powder itself contains no living cells.

      Animal models using BioCartilage have provided data that supports the assertion that the
      BioCartilage augmentation may improve outcomes for patients who receive it; however there is
      currently no published human clinical outcomes data available for using BioCartilage (Abrams
      et al., 2013).
observational model: Cohort
time perspective: Prospective
measure: MRI Repair Tissue Comparison
time frame: 1 year post-operatively
description: The primary endpoint is to determine whether subjects receiving a marrow stimulating procedure (MSP) augmented with BioCartilage have improved outcomes (MRI) compared to subjects who receive MSP without the use of BioCartilage. Quantitative (%fill) and qualitative (tissue quality) MRI assessments of repair tissue will be performed by a musculoskeletal (MSK) radiologist who is blinded to treatment group, and compared for differences between treatment groups.
measure: Short Form-12 Health Survey (SF-12)
time frame: Approximately 2 years
description: The 12-item Short Form Survey (SF-12) is a general health questionnaire. The SF-12 was constructed using questions drawn from each of the 8 dimensions of the MOS 36 item Short Form Survey (SF-36). It is designed to have similar performance to the SF-36, while taking less time to complete. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). Physical and Mental Health Composite Scores (PCS & MCS) are computed using the scores of twelve questions and range from 0 to 100, where a zero score indicates the lowest level of health measured by the scales and 100 indicates the highest level of health.
measure: Marx Activity Rating Scale
time frame: Approximately 2 years
description: The Marx Scale consists of four questions concerning four activities or actions: running, cutting, deceleration, and pivoting. The patient or survey respondent is asked to report on the frequency with which they performed the activity in their healthiest state within the past year. The four knee functions are rated on a 5-point scale of frequency and scores are added up to a minimum score of 0 and a maximum of 16 points, with a higher score indicating more frequent participation.
measure: Knee Injury and Osteoarthritis Outcomes Score (KOOS)
time frame: Approximately 2 years
description: The Knee injury and Osteoarthritis Outcome Score (KOOS) assesses patient pain (9 items), other symptoms (7 items), function in daily living (17 items), function in sport and recreation (5 items), and knee related quality of life (4 items). Scores range from 0 to 100 with a score of 0 indicating the worst possible knee symptoms and 100 indicating no knee symptoms. The KOOS is a patient reported joint-specific score, which may be useful for assessing changes in knee pathology over time, with or without treatment.
measure: International Knee Documentation Committee (IKDC) Subjective Portion
time frame: Approximately 2 years
description: The IKDC Questionnaire is a subjective scale that provides patients with an overall function score. The questionnaire looks at 3 categories: symptoms, sports activity, and knee function. The symptoms subscale helps to evaluate things such as pain, stiffness, swelling and giving-way of the knee. Meanwhile, the sports activity subscale focuses on functions like going up and down the stairs, rising from a chair, squatting and jumping. The knee function subscale asks patients one simple question: how is their knee at present versus how was their knee prior to injury?
Scores are obtained by summing the individual items, then transforming the crude total to a scaled number that ranges from 0 to 100. This final number is interpreted as a measure of function with higher scores representing higher levels of function.
measure: Number of Participants Who Were Able To Return To Return to Work or Sports Activity
time frame: Approximately 2 years
description: This is a two question survey administered to subjects that obtains subjective data "Yes / No" regarding whether the subject has been able to return to work or sports activity since surgery.
arm group label: MSP with BioCartilage
description: Patients receiving marrow stimulating procedure with BioCartilage adjunct.
arm group label: MSP without BioCartilage
description: Patients receiving marrow stimulating procedure without BioCartilage.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James P Stannard, MD
role: Principal Investigator
affiliation: University of Missouri-Columbia
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Missouri-Columbia
investigator full name: James Stannard
investigator title: Principal Investigator
mesh term: Cartilage Diseases
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 