<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/NCT02208271</url>
  </required_header>
  <id_info>
    <org_study_id>HK003-14014</org_study_id>
    <nct_id>NCT02208271</nct_id>
  </id_info>
  <brief_title>A Validated Necrosis Assay to Determine the Need for Revision Surgery in Metal-on-metal Total Hip Arthroplasty</brief_title>
  <official_title>A Validated Necrosis Assay to Determine the Need for Revision Surgery in Metal-on-metal Total Hip Arthroplasty</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OrthoCarolina Research Institute, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Charlotte Orthopedic Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OrthoCarolina Research Institute, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for&#xD;
      adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.&#xD;
&#xD;
      A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal&#xD;
      revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant,&#xD;
      control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial&#xD;
      fluid will be obtained from all hips and used for biomarker testing. Additionally,&#xD;
      intraoperative assessment of tissue necrosis will be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Well-functioning MoM implants have shown an increase in serum cobalt and chromium (CoCr) ion&#xD;
      levels from the metal debris generated from the implant wear.However, the current evidence&#xD;
      suggests that measuring ion levels is unreliable and that increasing ion levels do not&#xD;
      correlate with tissue damage. In addition to measuring blood and synovial fluid metal ion&#xD;
      levels, ultrasound and MRI with metal artifact reduction sequences (MARS) have been utilized&#xD;
      to assess periarticular reactions secondary to metal wear debris. Despite metal reduction&#xD;
      software these scans are frequently difficult to interpret. While each of these tests has&#xD;
      merit, at the present time there is no single diagnostic test available which delineates the&#xD;
      key issue that demands urgent surgical intervention, i.e. tissue necrosis. It is important to&#xD;
      have a reliable test to guide surgeons and patients in the shared decision-making process of&#xD;
      when surgical intervention is necessary to prevent disabling tissue damage. For this reason,&#xD;
      the current study proposes an examination of preoperative serum samples of subjects in&#xD;
      addition to synovial fluid collected during revision surgery for biomarkers that may indicate&#xD;
      tissue necrosis. To maximize the chance of success of identifying serum biomarkers, all&#xD;
      samples will be analyzed using multianalyte assay, biomarker tests. The purpose of the study&#xD;
      is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue&#xD;
      reaction, or tissue necrosis, in a metal on metal total hip replacement.&#xD;
&#xD;
      A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal&#xD;
      revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant,&#xD;
      control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial&#xD;
      fluid will be obtained from all hips and used for biomarker testing. Additionally,&#xD;
      intraoperative assessment of tissue necrosis will be assessed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Suspended</overall_status>
  <why_stopped>
    The lab was acquired by another company and has put this study's samples on hold.&#xD;
  </why_stopped>
  <start_date type="Actual">August 4, 2014</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Actual">May 17, 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>The number of patients with serum and synovial fluid biomarkers</measure>
    <time_frame>participants will be followed for the duration of their hospital stay, an expected average of 2 hours</time_frame>
    <description>Blood Serum and Synovial fluid will be tested using a multi-analyte assay test</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of patients with tissue necrosis</measure>
    <time_frame>participants will be followed for the duration of their hospital stay, an expected average of 2 hours</time_frame>
    <description>Tissue necrosis will be assessed during total hip surgery.&#xD;
Tissue necrosis will be scored in subsets including: intraoperative tissue damage, histological necrosis score, histologic ALVAL score, inflammatory infiltrate, and tissue organization</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">174</enrollment>
  <condition>Arthritis, Failure of Total Hip</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>pre-operative total hip patients with no existing total hip implant</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metal on polyethylene</arm_group_label>
    <description>patients who have a failed metal on polyethylene total hip implant and are presenting for revision surgery</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metal on Metal</arm_group_label>
    <description>patients who have a failed metal on metal total hip implant and are presenting for revision surgery</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        A convenience sample of a total of 100 hip patients will be enrolled at orthopedic clinics.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients presenting for a metal on metal hip revision who have cobalt and chromium&#xD;
             metal ion levels tested within 6 months of the date of the planned revision surgery.&#xD;
&#xD;
          -  Patients presenting for a metal on poly hip revision&#xD;
&#xD;
          -  Revision hip patients must be greater than one year postoperative&#xD;
&#xD;
          -  The diagnosis at the time of the index, or primary, hip replacement was&#xD;
             osteoarthritis.&#xD;
&#xD;
          -  Patients who have hip osteoarthritis but have not had a total hip surgery (control)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients presenting for a metal on metal hip revision who have cobalt and chromium&#xD;
             metal ion levels tested &gt;6 months of the date of the planned revision&#xD;
&#xD;
          -  Patients with a total hip on the contralateral side.&#xD;
&#xD;
          -  Patients with a prior history of periprosthetic infection&#xD;
&#xD;
          -  Revision cases where the diagnosis at the time of the index, or primary, hip&#xD;
             replacement was not osteoarthritis.&#xD;
&#xD;
          -  Prisoners&#xD;
&#xD;
          -  Patients not willing to consent for the proposed treatment&#xD;
&#xD;
          -  Patients with an altered mental status&#xD;
&#xD;
          -  Active, concurrent metastatic infection&#xD;
&#xD;
          -  Active, superficial infection&#xD;
&#xD;
          -  Patients presenting for a metal on poly hip revision to treat trunionosis&#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>Thomas Fehring, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>OrthoCarolina Research Institute, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OrthoCarolina</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>MacDonald SJ. Metal-on-metal total hip arthroplasty: the concerns. Clin Orthop Relat Res. 2004 Dec;(429):86-93. doi: 10.1097/01.blo.0000150309.48474.8b.</citation>
    <PMID>15577471</PMID>
  </reference>
  <reference>
    <citation>Lindgren JU, Brismar BH, Wikstrom AC. Adverse reaction to metal release from a modular metal-on-polyethylene hip prosthesis. J Bone Joint Surg Br. 2011 Oct;93(10):1427-30. doi: 10.1302/0301-620X.93B10.27645.</citation>
    <PMID>21969447</PMID>
  </reference>
  <reference>
    <citation>Lombardi AV Jr, Barrack RL, Berend KR, Cuckler JM, Jacobs JJ, Mont MA, Schmalzried TP. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. J Bone Joint Surg Br. 2012 Nov;94(11 Suppl A):14-8. doi: 10.1302/0301-620X.94B11.30680.</citation>
    <PMID>23118373</PMID>
  </reference>
  <reference>
    <citation>Cobb AG, Schmalzreid TP. The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty. Proc Inst Mech Eng H. 2006 Feb;220(2):385-98. doi: 10.1243/09544119JEIM78.</citation>
    <PMID>16669404</PMID>
  </reference>
  <reference>
    <citation>Mabilleau G, Kwon YM, Pandit H, Murray DW, Sabokbar A. Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions. Acta Orthop. 2008 Dec;79(6):734-47. doi: 10.1080/17453670810016795.</citation>
    <PMID>19085489</PMID>
  </reference>
  <reference>
    <citation>Tower SS. Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am. 2010 Dec 1;92(17):2847-51. doi: 10.2106/JBJS.J.00125. Epub 2010 Oct 29. No abstract available.</citation>
    <PMID>21037026</PMID>
  </reference>
  <reference>
    <citation>Campbell P, Ebramzadeh E, Nelson S, Takamura K, De Smet K, Amstutz HC. Histological features of pseudotumor-like tissues from metal-on-metal hips. Clin Orthop Relat Res. 2010 Sep;468(9):2321-7. doi: 10.1007/s11999-010-1372-y.</citation>
    <PMID>20458645</PMID>
  </reference>
  <reference>
    <citation>Leopold SS, Berger RA, Patterson L, Skipor AK, Urban RM, Jacobs JJ. Serum titanium level for diagnosis of a failed, metal-backed patellar component. J Arthroplasty. 2000 Oct;15(7):938-43. doi: 10.1054/arth.2000.6632.</citation>
    <PMID>11061457</PMID>
  </reference>
  <reference>
    <citation>Griffin WL, Fehring TK, Kudrna JC, Schmidt RH, Christie MJ, Odum SM, Dennos AC. Are metal ion levels a useful trigger for surgical intervention? J Arthroplasty. 2012 Sep;27(8 Suppl):32-6. doi: 10.1016/j.arth.2012.03.020. Epub 2012 May 17.</citation>
    <PMID>22608683</PMID>
  </reference>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 17, 2014</study_first_submitted>
  <study_first_submitted_qc>August 4, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <last_update_submitted>April 11, 2023</last_update_submitted>
  <last_update_submitted_qc>April 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tissue necrosis</keyword>
  <keyword>metal on metal total hip</keyword>
  <keyword>biomarker</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Necrosis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02208271
org study id: HK003-14014
nct id: NCT02208271
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of the study is to develop a biomarker assay to be used as a diagnostic tool for
      adverse local tissue reaction, or tissue necrosis, in a metal on metal total hip replacement.

      A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal
      revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant,
      control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial
      fluid will be obtained from all hips and used for biomarker testing. Additionally,
      intraoperative assessment of tissue necrosis will be assessed.
Well-functioning MoM implants have shown an increase in serum cobalt and chromium (CoCr) ion
      levels from the metal debris generated from the implant wear.However, the current evidence
      suggests that measuring ion levels is unreliable and that increasing ion levels do not
      correlate with tissue damage. In addition to measuring blood and synovial fluid metal ion
      levels, ultrasound and MRI with metal artifact reduction sequences (MARS) have been utilized
      to assess periarticular reactions secondary to metal wear debris. Despite metal reduction
      software these scans are frequently difficult to interpret. While each of these tests has
      merit, at the present time there is no single diagnostic test available which delineates the
      key issue that demands urgent surgical intervention, i.e. tissue necrosis. It is important to
      have a reliable test to guide surgeons and patients in the shared decision-making process of
      when surgical intervention is necessary to prevent disabling tissue damage. For this reason,
      the current study proposes an examination of preoperative serum samples of subjects in
      addition to synovial fluid collected during revision surgery for biomarkers that may indicate
      tissue necrosis. To maximize the chance of success of identifying serum biomarkers, all
      samples will be analyzed using multianalyte assay, biomarker tests. The purpose of the study
      is to develop a biomarker assay to be used as a diagnostic tool for adverse local tissue
      reaction, or tissue necrosis, in a metal on metal total hip replacement.

      A convenience sample of a total of 100 hip patients will be enrolled: 50 metal-on-metal
      revision hips, 25 metal-on-poly revision hips, and 25 pre-operative total hips (no implant,
      control group) will be enrolled. Preoperative blood serum samples and intraoperative synovial
      fluid will be obtained from all hips and used for biomarker testing. Additionally,
      intraoperative assessment of tissue necrosis will be assessed.
observational model: Cohort
time perspective: Prospective
measure: The number of patients with serum and synovial fluid biomarkers
time frame: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
description: Blood Serum and Synovial fluid will be tested using a multi-analyte assay test
measure: The number of patients with tissue necrosis
time frame: participants will be followed for the duration of their hospital stay, an expected average of 2 hours
description: Tissue necrosis will be assessed during total hip surgery.
Tissue necrosis will be scored in subsets including: intraoperative tissue damage, histological necrosis score, histologic ALVAL score, inflammatory infiltrate, and tissue organization
arm group label: Control
description: pre-operative total hip patients with no existing total hip implant
arm group label: Metal on polyethylene
description: patients who have a failed metal on polyethylene total hip implant and are presenting for revision surgery
arm group label: Metal on Metal
description: patients who have a failed metal on metal total hip implant and are presenting for revision surgery
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Fehring, MD
role: Principal Investigator
affiliation: OrthoCarolina Research Institute, Inc.
facility: 
country: United States
citation: MacDonald SJ. Metal-on-metal total hip arthroplasty: the concerns. Clin Orthop Relat Res. 2004 Dec;(429):86-93. doi: 10.1097/01.blo.0000150309.48474.8b.
PMID: 15577471
citation: Lindgren JU, Brismar BH, Wikstrom AC. Adverse reaction to metal release from a modular metal-on-polyethylene hip prosthesis. J Bone Joint Surg Br. 2011 Oct;93(10):1427-30. doi: 10.1302/0301-620X.93B10.27645.
PMID: 21969447
citation: Lombardi AV Jr, Barrack RL, Berend KR, Cuckler JM, Jacobs JJ, Mont MA, Schmalzried TP. The Hip Society: algorithmic approach to diagnosis and management of metal-on-metal arthroplasty. J Bone Joint Surg Br. 2012 Nov;94(11 Suppl A):14-8. doi: 10.1302/0301-620X.94B11.30680.
PMID: 23118373
citation: Cobb AG, Schmalzreid TP. The clinical significance of metal ion release from cobalt-chromium metal-on-metal hip joint arthroplasty. Proc Inst Mech Eng H. 2006 Feb;220(2):385-98. doi: 10.1243/09544119JEIM78.
PMID: 16669404
citation: Mabilleau G, Kwon YM, Pandit H, Murray DW, Sabokbar A. Metal-on-metal hip resurfacing arthroplasty: a review of periprosthetic biological reactions. Acta Orthop. 2008 Dec;79(6):734-47. doi: 10.1080/17453670810016795.
PMID: 19085489
citation: Tower SS. Arthroprosthetic cobaltism: neurological and cardiac manifestations in two patients with metal-on-metal arthroplasty: a case report. J Bone Joint Surg Am. 2010 Dec 1;92(17):2847-51. doi: 10.2106/JBJS.J.00125. Epub 2010 Oct 29. No abstract available.
PMID: 21037026
citation: Campbell P, Ebramzadeh E, Nelson S, Takamura K, De Smet K, Amstutz HC. Histological features of pseudotumor-like tissues from metal-on-metal hips. Clin Orthop Relat Res. 2010 Sep;468(9):2321-7. doi: 10.1007/s11999-010-1372-y.
PMID: 20458645
citation: Leopold SS, Berger RA, Patterson L, Skipor AK, Urban RM, Jacobs JJ. Serum titanium level for diagnosis of a failed, metal-backed patellar component. J Arthroplasty. 2000 Oct;15(7):938-43. doi: 10.1054/arth.2000.6632.
PMID: 11061457
citation: Griffin WL, Fehring TK, Kudrna JC, Schmidt RH, Christie MJ, Odum SM, Dennos AC. Are metal ion levels a useful trigger for surgical intervention? J Arthroplasty. 2012 Sep;27(8 Suppl):32-6. doi: 10.1016/j.arth.2012.03.020. Epub 2012 May 17.
PMID: 22608683
responsible party type: Sponsor
mesh term: Necrosis