<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/NCT03803839</url>
  </required_header>
  <id_info>
    <org_study_id>Ei tiedossa</org_study_id>
    <nct_id>NCT03803839</nct_id>
  </id_info>
  <brief_title>Locally Administered Clodronate in the Prevention of Aseptic Implant Loosening</brief_title>
  <official_title>Could the Intra-operative Clodronate Rinsing Improve the Integration of the Femoral Stem in a Prospective, Double-blinded, Randomized, Placebo-controlled Clinical RSA-study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oulu</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Oulu</source>
  <oversight_info>
    <has_dmc>No</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>
      Periprosthetic bone-loss after total hip arthroplasty (THA), detected as an early migration&#xD;
      of the prosthesis, may predict later loosening. The investigators hypothesized that by&#xD;
      reducing bone resorption after THA with bisphosphonates, it might be possible to achieve&#xD;
      better early fixation of the implant.&#xD;
&#xD;
      Nineteen patients suffering arthrosis were recruited to a prospective, double-blinded,&#xD;
      randomized, placebo-controlled clinical pilot trial. Patients were operated with an&#xD;
      uncemented Bimetric stem with tantalum markers, the acetabular cup and liner were chosen by&#xD;
      the surgeon. The femoral proximal intramedullary canal was rinsed with 1mM (millimole)&#xD;
      clodronate, that was done by adding the clodronate to the 1000 ml 0.9% NaCl (sodium chloride)&#xD;
      in nine patients and rinsing solution was the pure 0.9% NaCl for 10 patients. These rinsing&#xD;
      packages were labeled only with the code from the pharmacy of the hospital. These patients&#xD;
      were followed for two years using radiostereometric analysis (RSA), dual energy x-ray&#xD;
      absorptiometry (DXA) and the Harris hip score (HHS).&#xD;
&#xD;
      The purpose of the investigator's study was to examine whether the local intraoperative&#xD;
      administration of clodronate could reduce periprosthetic bone loss and further stem migration&#xD;
      after primary THA.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 26, 2004</start_date>
  <completion_date type="Actual">March 12, 2014</completion_date>
  <primary_completion_date type="Actual">March 12, 2014</primary_completion_date>
  <phase>Early Phase 1</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>In this prospective, double-blinded, randomized, placebo-controlled clinical trial with two years follow-up period the investigators rinsed the proximal intramedullary cavity of the femur with either clodronate (60 mg clodronate in 1000 ml saline) or saline (1000 ml saline) prior to the application of the femoral stem.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Patients were randomized into two treatment groups; either the clodronate or a placebo group. All patients, surgeons and other personnel in the operating theatre were blinded as to the patients' study group.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Maximal total point motion (MTPM) - migration of the femoral stem</measure>
    <time_frame>0 to 24 months</time_frame>
    <description>It represents the length of the translation vector of the point in a rigid body that has the greatest motion. It can only have positive values, and is not normally distributed. The reason for using MTPM is that in many cases, motion implies a biological effect of some kind and this effect is liable to be greatest at the point of maximum motion. The parameter has been measured by RSA-methods, which is an accurate method of determining the migration and wear of orthopaedic implants: it determine the precise location of two distinct objects relative to each other in three dimension such as the relative position of the femoral component and the proximal femur. In radiostereometric analysis the position in space of the original object is reconstructed from a two dimensional x-ray film using tantalum beads. Movement between segments is then calculated by localizing each segment in a coordinate system. Lower values represent a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Bone mineral density (BMD) in 7 Gruen zones</measure>
    <time_frame>0 to 24 months</time_frame>
    <description>BMD was measured by dual-energy X-ray absorptiometry, DXA. In clinical use, precision errors are &lt; 5 %. To evaluate the horizontal linear distribution of the BMD, seven Gruen zones, peri-prosthetic sub-regions of interest, ROI (region of interest) were calculated by the software on the anteroposterior view of the proximal femur. The value of BMD is g/cm2 and it estimates the strength of the bone. Higher values/lesser decrease in values represent a better outcome.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Migration of femoral stem</measure>
    <time_frame>0 to 24 months</time_frame>
    <description>Subsidence and vertical movement of the femoral stem (scale micrometers), x-, y- and z-translations. Parameters were measured using RSA-methods and the scaling is linear. Lower values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>The maximal (MTPM) maximal total point motion</measure>
    <time_frame>3 to 24 months</time_frame>
    <description>The maximal MTPM value after 3 months when the expected integration of stem should have happened. Lower values represent a better outcome.</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlation between baseline BMD and the maximal MTPM</measure>
    <time_frame>BMD (0 month) - the maximal MTPM 3 to 24 months</time_frame>
    <description>This parameters summarize the BMD and RSA values together. The investigators have planned it to evaluate the correlation between the quality of periprosthetic bone in baseline and the migration of femoral stem during 2 years follow-up period between the study groups.</description>
  </other_outcome>
  <other_outcome>
    <measure>Harris Hip Score (HHS)</measure>
    <time_frame>0 to 24 months</time_frame>
    <description>Harris Hip Score (HHS) is a clinician-based outcome measure, health status scale, that is frequently used to measure the outcome of total hip arthroplasty. It is measured by questionnaire that give points from 0 to 100. Higher values represent a better outcome.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Hip Arthrosis</condition>
  <arm_group>
    <arm_group_label>Clodronate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 mM clodronate (60 mg in 1000 ml saline) was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the clodronate solution. The time for rinsing was about one minute.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>1000 ml saline was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the saline solution. The time for rinsing was about one minute.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clodronate</intervention_name>
    <arm_group_label>Clodronate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline</intervention_name>
    <arm_group_label>Saline</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  hip arthrosis and&#xD;
&#xD;
          -  a primary THA was planned&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  renal insufficiency&#xD;
&#xD;
          -  hypercalcemia&#xD;
&#xD;
          -  malignant tumors&#xD;
&#xD;
          -  contemporaneously treatment with another bisphosphonate or aminoglycoside&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>73 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 15, 2019</study_first_posted>
  <last_update_submitted>January 16, 2019</last_update_submitted>
  <last_update_submitted_qc>January 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>RSA</keyword>
  <keyword>DXA</keyword>
  <keyword>Bisphosphonates</keyword>
  <keyword>Migration of stem</keyword>
  <keyword>Aseptic loosening of prosthesis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Osteoarthritis</mesh_term>
    <mesh_term>Osteoarthritis, Hip</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clodronic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data for all primary and secondary outcome data will be made available.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Data will be available after submitting the results to the scientific journals and five years after the publication.</ipd_time_frame>
    <ipd_access_criteria>Data Access requests will be reviewed By an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.</ipd_access_criteria>
  </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/NCT03803839
org study id: Ei tiedossa
nct id: NCT03803839
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Periprosthetic bone-loss after total hip arthroplasty (THA), detected as an early migration
      of the prosthesis, may predict later loosening. The investigators hypothesized that by
      reducing bone resorption after THA with bisphosphonates, it might be possible to achieve
      better early fixation of the implant.

      Nineteen patients suffering arthrosis were recruited to a prospective, double-blinded,
      randomized, placebo-controlled clinical pilot trial. Patients were operated with an
      uncemented Bimetric stem with tantalum markers, the acetabular cup and liner were chosen by
      the surgeon. The femoral proximal intramedullary canal was rinsed with 1mM (millimole)
      clodronate, that was done by adding the clodronate to the 1000 ml 0.9% NaCl (sodium chloride)
      in nine patients and rinsing solution was the pure 0.9% NaCl for 10 patients. These rinsing
      packages were labeled only with the code from the pharmacy of the hospital. These patients
      were followed for two years using radiostereometric analysis (RSA), dual energy x-ray
      absorptiometry (DXA) and the Harris hip score (HHS).

      The purpose of the investigator's study was to examine whether the local intraoperative
      administration of clodronate could reduce periprosthetic bone loss and further stem migration
      after primary THA.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: In this prospective, double-blinded, randomized, placebo-controlled clinical trial with two years follow-up period the investigators rinsed the proximal intramedullary cavity of the femur with either clodronate (60 mg clodronate in 1000 ml saline) or saline (1000 ml saline) prior to the application of the femoral stem.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Patients were randomized into two treatment groups; either the clodronate or a placebo group. All patients, surgeons and other personnel in the operating theatre were blinded as to the patients' study group.
measure: Maximal total point motion (MTPM) - migration of the femoral stem
time frame: 0 to 24 months
description: It represents the length of the translation vector of the point in a rigid body that has the greatest motion. It can only have positive values, and is not normally distributed. The reason for using MTPM is that in many cases, motion implies a biological effect of some kind and this effect is liable to be greatest at the point of maximum motion. The parameter has been measured by RSA-methods, which is an accurate method of determining the migration and wear of orthopaedic implants: it determine the precise location of two distinct objects relative to each other in three dimension such as the relative position of the femoral component and the proximal femur. In radiostereometric analysis the position in space of the original object is reconstructed from a two dimensional x-ray film using tantalum beads. Movement between segments is then calculated by localizing each segment in a coordinate system. Lower values represent a better outcome.
measure: Bone mineral density (BMD) in 7 Gruen zones
time frame: 0 to 24 months
description: BMD was measured by dual-energy X-ray absorptiometry, DXA. In clinical use, precision errors are < 5 %. To evaluate the horizontal linear distribution of the BMD, seven Gruen zones, peri-prosthetic sub-regions of interest, ROI (region of interest) were calculated by the software on the anteroposterior view of the proximal femur. The value of BMD is g/cm2 and it estimates the strength of the bone. Higher values/lesser decrease in values represent a better outcome.
measure: Migration of femoral stem
time frame: 0 to 24 months
description: Subsidence and vertical movement of the femoral stem (scale micrometers), x-, y- and z-translations. Parameters were measured using RSA-methods and the scaling is linear. Lower values represent a better outcome.
measure: The maximal (MTPM) maximal total point motion
time frame: 3 to 24 months
description: The maximal MTPM value after 3 months when the expected integration of stem should have happened. Lower values represent a better outcome.
measure: Correlation between baseline BMD and the maximal MTPM
time frame: BMD (0 month) - the maximal MTPM 3 to 24 months
description: This parameters summarize the BMD and RSA values together. The investigators have planned it to evaluate the correlation between the quality of periprosthetic bone in baseline and the migration of femoral stem during 2 years follow-up period between the study groups.
measure: Harris Hip Score (HHS)
time frame: 0 to 24 months
description: Harris Hip Score (HHS) is a clinician-based outcome measure, health status scale, that is frequently used to measure the outcome of total hip arthroplasty. It is measured by questionnaire that give points from 0 to 100. Higher values represent a better outcome.
arm group label: Clodronate
arm group type: Active Comparator
description: 1 mM clodronate (60 mg in 1000 ml saline) was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the clodronate solution. The time for rinsing was about one minute.
arm group label: Saline
arm group type: Placebo Comparator
description: 1000 ml saline was used intraoperatively during total hip arthroplasty: before installation of the prosthesis, the rinsing was performed with pulsatile lavage using the saline solution. The time for rinsing was about one minute.
intervention type: Drug
intervention name: Clodronate
arm group label: Clodronate
intervention type: Drug
intervention name: Saline
arm group label: Saline
criteria: 
gender: All
minimum age: N/A
maximum age: 73 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Osteoarthritis
mesh term: Osteoarthritis, Hip
mesh term: Clodronic Acid
sharing ipd: Yes
ipd description: De-identified individual participant data for all primary and secondary outcome data will be made available.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Data will be available after submitting the results to the scientific journals and five years after the publication.
ipd access criteria: Data Access requests will be reviewed By an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.