<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/NCT03780036</url>
  </required_header>
  <id_info>
    <org_study_id>0619-18-TLV</org_study_id>
    <nct_id>NCT03780036</nct_id>
  </id_info>
  <brief_title>Megaprosthetic Implants the Next Generation (MING)</brief_title>
  <acronym>MING</acronym>
  <official_title>A Randomised, Single Blind Study Assessing Radiological Outcomes for Massive Segmental Femoral Replacements Using Either Porous Collar or Porous Collar With HA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tel-Aviv Sourasky Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Adler Ortho, iEthos Medical Ltd</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Tel-Aviv Sourasky Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an interventional randomized controlled trial that will compare patients who&#xD;
      underwent segmental hip replacement using mega-implants with either porous collar or porous&#xD;
      collar with HA. Patient recruitment will continue for 18 months. Parameters to be&#xD;
      investigated are radiographic measures of bone incorporation into the implants, as well as&#xD;
      patient functional outcomes. Clinical follow-up will last for 24 months for each patient.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BACKGROUND The current surgical treatment of bone cancer patients requires usage of massive&#xD;
      endoprosthetic bone implants. The incidence of aseptic loosening is a major cause of&#xD;
      prosthesis failure in these patients. Exploring ways to reduce such failures would allow&#xD;
      extending longevity of massive implants in a relatively young population.&#xD;
&#xD;
      Current published literature stipulates that osteointegration could improve longevity of&#xD;
      massive implants. Evidence suggests that usage of osteointegrated hydroxyapatite (HA) coated&#xD;
      collar would reduce the incidence of aseptic loosening around the cemented intramedullary&#xD;
      stem in distal femoral bone prosthesis.&#xD;
&#xD;
      Our study aims to compare radiological outcome in 2 groups:&#xD;
&#xD;
        -  A porous collar for either distal or proximal femoral replacements&#xD;
&#xD;
        -  A porous collar with hydroxyapatite (HA) for either distal or proximal femoral&#xD;
           replacements The porous collar will be manufactured by Adler Ortho using additive layer&#xD;
           manufacturing technology.&#xD;
&#xD;
      STUDY OBJECTIVES The study will review the use of massive segmental replacements in the&#xD;
      femur, which have a porous collar with and without HA.&#xD;
&#xD;
      Primary objectives:&#xD;
&#xD;
      The primary objective of the study will be to assess radiological outcome by assessing bony&#xD;
      growth into the collar.&#xD;
&#xD;
      Secondary objectives The secondary objective will focus on assessing patient reported outcome&#xD;
      measures (VAS pain score and other PROMS)&#xD;
&#xD;
      STUDY DESIGN&#xD;
&#xD;
      Patients will be identified in the outpatient setting as suitable for entry into the trial&#xD;
      based on the inclusion and exclusion criteria as set out below.&#xD;
&#xD;
      Patients will be randomised into one of the two groups of the study, due to the nature of&#xD;
      intervention this will be a single blind study.&#xD;
&#xD;
      Patients will undergo plain radiographs immediately post-operatively, at 6 months&#xD;
      post-operatively, 12 months post-operatively and 24 months post-operatively. Standard&#xD;
      protocol radiographs of the relevant limb will be taken in the antero-posterior (AP) and&#xD;
      medial-lateral (ML) planes (x2 AP and x2 laterals to cover the prosthesis).&#xD;
&#xD;
      At 12 months and 24 months post-operatively patients will receive a CT scan (cover whole&#xD;
      prosthesis, extended CT - knee, pelvis), which will be used to image bone growth within the&#xD;
      porous collars.&#xD;
&#xD;
      For plain radiographs a scoring system for extra-cortical bone formation will be made&#xD;
      according to Coathup et al, 2013. This will be quantified radiologically in four zones&#xD;
      (medial and lateral aspects on AP radiographs; anterior and posterior aspects on ML&#xD;
      radiographs). Extracortical bone separated from the implant by a clear radiolucent line is&#xD;
      not considered in grown and will be scored 0. A score of 1 will represent extracortical bone&#xD;
      (&gt;5mm think and &gt;1mm long) in contact with the implant surface in any of the four previously&#xD;
      described zones. The maximum score will be 4, denoting extracortical bone growth in all four&#xD;
      zones.&#xD;
&#xD;
      Patients identified and consented in clinic for entry into study. Randomisation prior to&#xD;
      surgical date. Baseline X-ray and CT done pre-operatively as per current pre-operative&#xD;
      guidelines.&#xD;
&#xD;
      Pre-operative bloods and joint aspiration done to definitively rule out infection in revision&#xD;
      patients Pre-operative VAS pain score on admission&#xD;
&#xD;
      Joint replacement done - clarify antibiotic prophylaxis with surgeons - induction + extended&#xD;
      post-operative antibiotic prophylaxis&#xD;
&#xD;
      Post-operative Toronto Extremity Salvage Score (TESS) to assess physical functioning for all&#xD;
      patients. TESS repeated at 6, 12 and 24 months to assess progress post-operatively -&#xD;
      correlating with radiographical findings.&#xD;
&#xD;
      Surgery related data including theatre time, intra-operative blood loss and intra- and&#xD;
      post-operative complications will be recorded for all patients.&#xD;
&#xD;
      Immediate post-operative, 6, 12 and 24 monthly X-rays (x2 AP and x2 laterals to cover the&#xD;
      prosthesis); 12 and 24 monthly CT (cover whole prosthesis, extended CT - knee, pelvis) X-rays&#xD;
      and CT reported by scores calculated as previously described.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 1, 2019</start_date>
  <completion_date type="Anticipated">August 1, 2022</completion_date>
  <primary_completion_date type="Anticipated">August 1, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Random assignment of patients into one of the two study arms: porous collar magaprostheses or porous collar with HA megaprostheses.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>The participant will not know which implant was used for segmental replacement of his or hear femur.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Bone incorporation</measure>
    <time_frame>24 months</time_frame>
    <description>Radiographic evidence of bony growth into the collar</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Functional outcome - Visual Analogue Pain Scale</measure>
    <time_frame>24 months</time_frame>
    <description>Reporting of pain levels (from 1 to 10)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome - a physical functioning score</measure>
    <time_frame>24 months</time_frame>
    <description>Toronto Extremity Salvage Score (TESS) for lower extremity</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Bone Neoplasm of Hip (Diagnosis)</condition>
  <arm_group>
    <arm_group_label>porous collar</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with neoplasm of femur bone who require segmental bone resection and replasement with a large prosthesis would receive an implant which collar (a circular part that comes into direct contact with the remaining bone) will be porous, to allow for bone ingrowth and stabilization of the implant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>porous collar with hydroxyapathite</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with neoplasm of femur bone who require segmental bone resection and replasement with a large prosthesis would receive an implant which collar (a circular part that comes into direct contact with the remaining bone) will be porous and covered with hydroxyapathite particles, to allow for bone ingrowth and stabilization of the implant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Megaprosthetic Implants the Next Generation (MING)</intervention_name>
    <description>Use of either porous of porous+hydroxyapathite collars.</description>
    <arm_group_label>porous collar</arm_group_label>
    <arm_group_label>porous collar with hydroxyapathite</arm_group_label>
    <other_name>Segmental bone replacement</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Bone cancer patients requiring primary or revision femoral segmental replacements&#xD;
             (excluding infections) and non-cancer patients requiring revision femoral segment&#xD;
             replacement for aseptic loosening (excluding infections)&#xD;
&#xD;
          -  Male or female, aged 18-80 years&#xD;
&#xD;
          -  Participants willing and able to give informed consent for participation in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants unwilling or unable to give informed consent for participation in the&#xD;
             study&#xD;
&#xD;
          -  Patients undergoing revision due to infection, identified by positive growth from&#xD;
             joint aspiration OR elevated pre-operative inflammatory markers OR radiographical&#xD;
             evidence of prosthetic joint infection&#xD;
&#xD;
          -  Bone cancer patients presenting with pathological fractures requiring segmental&#xD;
             femoral replacement&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Haggai Schermann, MD, MPH</last_name>
    <phone>528771014</phone>
    <phone_ext>972</phone_ext>
    <email>sheralmi@bu.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Solomon Dadia, MD</last_name>
    <email>dadias@tlvmc.gov.il</email>
  </overall_contact_backup>
  <reference>
    <citation>Coathup MJ, Sanghrajka A, Aston WJ, Gikas PD, Pollock RC, Cannon SR, Skinner JA, Briggs TW, Blunn GW. Hydroxyapatite-coated collars reduce radiolucent line progression in cemented distal femoral bone tumor implants. Clin Orthop Relat Res. 2015 Apr;473(4):1505-14. doi: 10.1007/s11999-014-4116-6. Epub 2015 Jan 30.</citation>
    <PMID>25634027</PMID>
  </reference>
  <reference>
    <citation>Coathup MJ, Batta V, Pollock RC, Aston WJ, Cannon SR, Skinner JA, Briggs TW, Unwin PS, Blunn GW. Long-term survival of cemented distal femoral endoprostheses with a hydroxyapatite-coated collar: a histological study and a radiographic follow-up. J Bone Joint Surg Am. 2013 Sep 4;95(17):1569-75. doi: 10.2106/JBJS.L.00362.</citation>
    <PMID>24005197</PMID>
  </reference>
  <reference>
    <citation>Mumith A, Coathup M, Chimutengwende-Gordon M, Aston W, Briggs T, Blunn G. Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study. Bone Joint J. 2017 Feb;99-B(2):276-282. doi: 10.1302/0301-620X.99B2.BJJ-2016-0584.R1.</citation>
    <PMID>28148673</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>December 17, 2018</last_update_submitted>
  <last_update_submitted_qc>December 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bone Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>De-identified data will be analyzed, and its summary will be shared with other researchers.</ipd_description>
  </patient_data>
  <!-- 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/NCT03780036
org study id: 0619-18-TLV
nct id: NCT03780036
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is an interventional randomized controlled trial that will compare patients who
      underwent segmental hip replacement using mega-implants with either porous collar or porous
      collar with HA. Patient recruitment will continue for 18 months. Parameters to be
      investigated are radiographic measures of bone incorporation into the implants, as well as
      patient functional outcomes. Clinical follow-up will last for 24 months for each patient.
BACKGROUND The current surgical treatment of bone cancer patients requires usage of massive
      endoprosthetic bone implants. The incidence of aseptic loosening is a major cause of
      prosthesis failure in these patients. Exploring ways to reduce such failures would allow
      extending longevity of massive implants in a relatively young population.

      Current published literature stipulates that osteointegration could improve longevity of
      massive implants. Evidence suggests that usage of osteointegrated hydroxyapatite (HA) coated
      collar would reduce the incidence of aseptic loosening around the cemented intramedullary
      stem in distal femoral bone prosthesis.

      Our study aims to compare radiological outcome in 2 groups:

        -  A porous collar for either distal or proximal femoral replacements

        -  A porous collar with hydroxyapatite (HA) for either distal or proximal femoral
           replacements The porous collar will be manufactured by Adler Ortho using additive layer
           manufacturing technology.

      STUDY OBJECTIVES The study will review the use of massive segmental replacements in the
      femur, which have a porous collar with and without HA.

      Primary objectives:

      The primary objective of the study will be to assess radiological outcome by assessing bony
      growth into the collar.

      Secondary objectives The secondary objective will focus on assessing patient reported outcome
      measures (VAS pain score and other PROMS)

      STUDY DESIGN

      Patients will be identified in the outpatient setting as suitable for entry into the trial
      based on the inclusion and exclusion criteria as set out below.

      Patients will be randomised into one of the two groups of the study, due to the nature of
      intervention this will be a single blind study.

      Patients will undergo plain radiographs immediately post-operatively, at 6 months
      post-operatively, 12 months post-operatively and 24 months post-operatively. Standard
      protocol radiographs of the relevant limb will be taken in the antero-posterior (AP) and
      medial-lateral (ML) planes (x2 AP and x2 laterals to cover the prosthesis).

      At 12 months and 24 months post-operatively patients will receive a CT scan (cover whole
      prosthesis, extended CT - knee, pelvis), which will be used to image bone growth within the
      porous collars.

      For plain radiographs a scoring system for extra-cortical bone formation will be made
      according to Coathup et al, 2013. This will be quantified radiologically in four zones
      (medial and lateral aspects on AP radiographs; anterior and posterior aspects on ML
      radiographs). Extracortical bone separated from the implant by a clear radiolucent line is
      not considered in grown and will be scored 0. A score of 1 will represent extracortical bone
      (>5mm think and >1mm long) in contact with the implant surface in any of the four previously
      described zones. The maximum score will be 4, denoting extracortical bone growth in all four
      zones.

      Patients identified and consented in clinic for entry into study. Randomisation prior to
      surgical date. Baseline X-ray and CT done pre-operatively as per current pre-operative
      guidelines.

      Pre-operative bloods and joint aspiration done to definitively rule out infection in revision
      patients Pre-operative VAS pain score on admission

      Joint replacement done - clarify antibiotic prophylaxis with surgeons - induction + extended
      post-operative antibiotic prophylaxis

      Post-operative Toronto Extremity Salvage Score (TESS) to assess physical functioning for all
      patients. TESS repeated at 6, 12 and 24 months to assess progress post-operatively -
      correlating with radiographical findings.

      Surgery related data including theatre time, intra-operative blood loss and intra- and
      post-operative complications will be recorded for all patients.

      Immediate post-operative, 6, 12 and 24 monthly X-rays (x2 AP and x2 laterals to cover the
      prosthesis); 12 and 24 monthly CT (cover whole prosthesis, extended CT - knee, pelvis) X-rays
      and CT reported by scores calculated as previously described.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Random assignment of patients into one of the two study arms: porous collar magaprostheses or porous collar with HA megaprostheses.
primary purpose: Treatment
masking: Single (Participant)
masking description: The participant will not know which implant was used for segmental replacement of his or hear femur.
measure: Bone incorporation
time frame: 24 months
description: Radiographic evidence of bony growth into the collar
measure: Functional outcome - Visual Analogue Pain Scale
time frame: 24 months
description: Reporting of pain levels (from 1 to 10)
measure: Functional outcome - a physical functioning score
time frame: 24 months
description: Toronto Extremity Salvage Score (TESS) for lower extremity
arm group label: porous collar
arm group type: Experimental
description: Patients with neoplasm of femur bone who require segmental bone resection and replasement with a large prosthesis would receive an implant which collar (a circular part that comes into direct contact with the remaining bone) will be porous, to allow for bone ingrowth and stabilization of the implant.
arm group label: porous collar with hydroxyapathite
arm group type: Experimental
description: Patients with neoplasm of femur bone who require segmental bone resection and replasement with a large prosthesis would receive an implant which collar (a circular part that comes into direct contact with the remaining bone) will be porous and covered with hydroxyapathite particles, to allow for bone ingrowth and stabilization of the implant.
intervention type: Device
intervention name: Megaprosthetic Implants the Next Generation (MING)
description: Use of either porous of porous+hydroxyapathite collars.
arm group label: porous collar
arm group label: porous collar with hydroxyapathite
other name: Segmental bone replacement
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Haggai Schermann, MD, MPH
phone: 528771014
phone ext: 972
email: sheralmi@bu.edu
last name: Solomon Dadia, MD
email: dadias@tlvmc.gov.il
citation: Coathup MJ, Sanghrajka A, Aston WJ, Gikas PD, Pollock RC, Cannon SR, Skinner JA, Briggs TW, Blunn GW. Hydroxyapatite-coated collars reduce radiolucent line progression in cemented distal femoral bone tumor implants. Clin Orthop Relat Res. 2015 Apr;473(4):1505-14. doi: 10.1007/s11999-014-4116-6. Epub 2015 Jan 30.
PMID: 25634027
citation: Coathup MJ, Batta V, Pollock RC, Aston WJ, Cannon SR, Skinner JA, Briggs TW, Unwin PS, Blunn GW. Long-term survival of cemented distal femoral endoprostheses with a hydroxyapatite-coated collar: a histological study and a radiographic follow-up. J Bone Joint Surg Am. 2013 Sep 4;95(17):1569-75. doi: 10.2106/JBJS.L.00362.
PMID: 24005197
citation: Mumith A, Coathup M, Chimutengwende-Gordon M, Aston W, Briggs T, Blunn G. Augmenting the osseointegration of endoprostheses using laser-sintered porous collars: an in vivo study. Bone Joint J. 2017 Feb;99-B(2):276-282. doi: 10.1302/0301-620X.99B2.BJJ-2016-0584.R1.
PMID: 28148673
responsible party type: Sponsor
mesh term: Bone Neoplasms
sharing ipd: No
ipd description: De-identified data will be analyzed, and its summary will be shared with other researchers.