<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/NCT01729195</url>
  </required_header>
  <id_info>
    <org_study_id>A204-CI-1</org_study_id>
    <secondary_id>Protocol 15526</secondary_id>
    <nct_id>NCT01729195</nct_id>
  </id_info>
  <brief_title>Ankle Syndesmosis Fixation by Antibiotic Releasing Bioabsorbable Screw</brief_title>
  <official_title>An Antibiotic Releasing Bone Screw: a Randomized Clinical Trial of Patients With Weber C Type Ankle Fractures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turku University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tampere University of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Turku University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This single-center randomized trial evaluates the efficacy and safety of a new bone screw&#xD;
      (antibiotic releasing bioabsorbable screw) in fixation of syndesmosis in patients with Weber&#xD;
      C-type ankle fractures. The comparison is made to subjects treated by conventional metal&#xD;
      screw fixation of the syndesmosis. The primary objective is to show that the antibiotic&#xD;
      releasing bioabsorbable screw is at least as good as the routinely used metal screw in&#xD;
      prevention of syndesmosis widening in patients with Weber C-type ankle fractures. The&#xD;
      secondary objective is to show that the clinical outcome of the ankle fracture treatment is&#xD;
      equal between patients treated by the antibiotic releasing bioabsorbable screw and the&#xD;
      conventional metal screw.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized parallel-group single centre study. All the patients enrolled will have&#xD;
      an acute, closed Weber C-type ankle fracture. The ankle syndesmosis will be fixed using the&#xD;
      new medical device (antibiotic containing bioabsorbable screw) or the routinely used device&#xD;
      (metal screw). The investigational antibiotic containing bioabsorbable screw for ankle&#xD;
      syndesmosis repair (the thread diameter 4.5 mm) will be made of bioabsorbable&#xD;
      poly(lactide-co-glycolide) (PLGA) 80:20 and ciprofloxacin, which is a bactericidal&#xD;
      antibiotic. The main purpose of the screw is to prevent syndesmosis widening after Weber&#xD;
      C-type of ankle fracture. The secondary function of the screw is to reduce the risk for&#xD;
      colonization of the implant with bacteria and subsequently prevent biomaterial-related&#xD;
      infection. In the control group, a stainless steel screw will be used. All patients will&#xD;
      receive the standard of care for concomitant fractures and other injuries of the ankle.&#xD;
&#xD;
      The key variables in the assessment will be radiostereometric (RSA) measurements of the&#xD;
      syndesmosis width, CT imaging of the ankle mortise and standard radiographic evaluation of&#xD;
      the syndesmosis width and ankle mortise. Clinical outcome of the ankle fracture treatment&#xD;
      will be measured using standardized outcome questionnaires (RAND-36, AAOS Foot and Ankle&#xD;
      Outcome Instrument, Olerud and Molander score, VAS pain scale). The follow-up of the patients&#xD;
      will be 52 weeks. The metal screw will be removed 8 weeks after fracture surgery. The&#xD;
      expected mechanical integrity of the bioabsorbable screw is 6 - 8 weeks, while the complete&#xD;
      absorption time of the bioabsorbable screw in human body is expected to be approximately two&#xD;
      years&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2006</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">January 2008</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Radiostereometric analysis of the width of the syndesmosis</measure>
    <time_frame>up to 12 weeks</time_frame>
    <description>Tantalum markers implanted during surgery into the fibula and tibia. Radiostereometric imaging allows to measure the three-dimensional displacement of the fibula in relation of the tibia.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Computed tomography in evaluation of the restoration of the normal anatomy</measure>
    <time_frame>Before surgery and repated at 0 and 12 weeks</time_frame>
    <description>CT imaging allows to evaluate the success in fracture reduction and the maintenance of the restored anatomy during the follow-up</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Conventional radiographic evaluation</measure>
    <time_frame>Before surgery and at 0, 6, 12 and 52 weeks</time_frame>
    <description>The method is applied to assess fracture reduction and retention, progress of fracture union, possible implant-related osteolysis and posttraumatic arthritis</description>
  </other_outcome>
  <other_outcome>
    <measure>Systemic exposure to the released antibiotic</measure>
    <time_frame>6 weeks</time_frame>
    <description>A venous sample for measurement of the serum concentration of ciprofloxacin using the HPLC-FLD method.</description>
  </other_outcome>
  <other_outcome>
    <measure>Functional recovery after ankle surgery</measure>
    <time_frame>Before surgery and at 12 and 52 weeks</time_frame>
    <description>Clinical examination of the ankle (range of motion, measurement of the circumferences of the calf) and standardized questionnaires (AAOS Foot and Ankle Outcome Instrument, Olerud-Molander Ankle Score, VAS-pain evaluation)</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Ankle Fracture</condition>
  <arm_group>
    <arm_group_label>Single-arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The syndesmosis injury of the patients will be fixed with a ciprofloxacin containing bioabsorbable PLGA bone screw or a stainless steel metal screw</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>A ciprofloxacin containing bioabsorbable PLGA bone screw</intervention_name>
    <description>The syndesmosis injury will be fixed the antibiotic releasing bioabsorbable bone screw or a standard metal screw. After surgery, the ankle will be immobilized in a cast for 6 weeks. The metal screw will be surgically removed at 8 weeks. The bioabsorbable screw will be left in place.</description>
    <arm_group_label>Single-arm</arm_group_label>
    <other_name>Manufactured in Tampere University of Technology/Bioretec Ltd</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  acute, closed Weber C-type ankle fracture&#xD;
&#xD;
          -  adult patients (age 18-70 years)&#xD;
&#xD;
          -  female subjects of child-bearing potential must have a negative pregnancy test and an&#xD;
             approved contraception for the study duration&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a previous fracture or infection of the injured ankle or the ipsilateral foot&#xD;
&#xD;
          -  significant associated soft-tissue injury&#xD;
&#xD;
          -  other long-bone fracture of the lower extremities&#xD;
&#xD;
          -  documented active infection at any anatomic site&#xD;
&#xD;
          -  a known metabolic skeletal disease (osteoporosis or osteomalasia) or a medication&#xD;
             affecting bone structure (such as corticosteroid treatment)&#xD;
&#xD;
          -  a pathological fracture&#xD;
&#xD;
          -  any underlying systemic disease (such as unbalanced diabetes mellitus or rheumatoid&#xD;
             disease) or a condition (such as alcoholism or drug abuse) which are known to affect&#xD;
             resistance to infection&#xD;
&#xD;
          -  history of prosthetic knee or hip replacement&#xD;
&#xD;
          -  pregnant women or nursing mothers&#xD;
&#xD;
          -  hypersensitivity to fluoroquinolones or related antibiotics (nalidixine acid)&#xD;
&#xD;
          -  any other condition that in the judgment of the investigator would prohibit the&#xD;
             subject from participating in the study or may hinder the collection of data and&#xD;
             interpretation of the results&#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_official>
    <last_name>Hannu T Aro, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Turku University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Turku University Hospital</name>
      <address>
        <city>Turku</city>
        <zip>20520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Finland</country>
  </location_countries>
  <link>
    <url>http://www.orthopaedics.utu.fi</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Makinen TJ, Veiranto M, Knuuti J, Jalava J, Tormala P, Aro HT. Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus. Bone. 2005 Feb;36(2):292-9. doi: 10.1016/j.bone.2004.11.009.</citation>
    <PMID>15780955</PMID>
  </reference>
  <reference>
    <citation>Makinen TJ, Mattila KT, Maattanen H, Aro HT. Comparison of digital and conventional radiostereometric image analysis in an ankle phantom model. Scand J Surg. 2005;94(3):233-8. doi: 10.1177/145749690509400311.</citation>
    <PMID>16259174</PMID>
  </reference>
  <reference>
    <citation>Niemela SM, Ikaheimo I, Koskela M, Veiranto M, Suokas E, Tormala P, Waris T, Ashammakhi N, Syrjala H. Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. J Biomed Mater Res B Appl Biomater. 2006 Jan;76(1):8-14. doi: 10.1002/jbm.b.30414.</citation>
    <PMID>16265660</PMID>
  </reference>
  <reference>
    <citation>Veiranto M, Tormala P, Suokas E. In vitro mechanical and drug release properties of bioabsorbable ciprofloxacin containing and neat self-reinforced P(L/DL)LA 70/30 fixation screws. J Mater Sci Mater Med. 2002 Dec;13(12):1259-63. doi: 10.1023/a:1021187331458.</citation>
    <PMID>15348674</PMID>
  </reference>
  <verification_date>February 2014</verification_date>
  <study_first_submitted>November 13, 2012</study_first_submitted>
  <study_first_submitted_qc>November 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <last_update_submitted>February 14, 2014</last_update_submitted>
  <last_update_submitted_qc>February 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bioabsorbable implant</keyword>
  <keyword>bone screw</keyword>
  <keyword>local antibiotic prophylaxis</keyword>
  <keyword>syndesmosis injury</keyword>
  <keyword>ankle fracture</keyword>
  <keyword>ciprofloxacin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fractures, Bone</mesh_term>
    <mesh_term>Ankle Fractures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ciprofloxacin</mesh_term>
  </intervention_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/NCT01729195
org study id: A204-CI-1
secondary id: Protocol 15526
nct id: NCT01729195
lead sponsor: 
collaborator: 
has dmc: No
This single-center randomized trial evaluates the efficacy and safety of a new bone screw
      (antibiotic releasing bioabsorbable screw) in fixation of syndesmosis in patients with Weber
      C-type ankle fractures. The comparison is made to subjects treated by conventional metal
      screw fixation of the syndesmosis. The primary objective is to show that the antibiotic
      releasing bioabsorbable screw is at least as good as the routinely used metal screw in
      prevention of syndesmosis widening in patients with Weber C-type ankle fractures. The
      secondary objective is to show that the clinical outcome of the ankle fracture treatment is
      equal between patients treated by the antibiotic releasing bioabsorbable screw and the
      conventional metal screw.
This is a randomized parallel-group single centre study. All the patients enrolled will have
      an acute, closed Weber C-type ankle fracture. The ankle syndesmosis will be fixed using the
      new medical device (antibiotic containing bioabsorbable screw) or the routinely used device
      (metal screw). The investigational antibiotic containing bioabsorbable screw for ankle
      syndesmosis repair (the thread diameter 4.5 mm) will be made of bioabsorbable
      poly(lactide-co-glycolide) (PLGA) 80:20 and ciprofloxacin, which is a bactericidal
      antibiotic. The main purpose of the screw is to prevent syndesmosis widening after Weber
      C-type of ankle fracture. The secondary function of the screw is to reduce the risk for
      colonization of the implant with bacteria and subsequently prevent biomaterial-related
      infection. In the control group, a stainless steel screw will be used. All patients will
      receive the standard of care for concomitant fractures and other injuries of the ankle.

      The key variables in the assessment will be radiostereometric (RSA) measurements of the
      syndesmosis width, CT imaging of the ankle mortise and standard radiographic evaluation of
      the syndesmosis width and ankle mortise. Clinical outcome of the ankle fracture treatment
      will be measured using standardized outcome questionnaires (RAND-36, AAOS Foot and Ankle
      Outcome Instrument, Olerud and Molander score, VAS pain scale). The follow-up of the patients
      will be 52 weeks. The metal screw will be removed 8 weeks after fracture surgery. The
      expected mechanical integrity of the bioabsorbable screw is 6 - 8 weeks, while the complete
      absorption time of the bioabsorbable screw in human body is expected to be approximately two
      years
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Radiostereometric analysis of the width of the syndesmosis
time frame: up to 12 weeks
description: Tantalum markers implanted during surgery into the fibula and tibia. Radiostereometric imaging allows to measure the three-dimensional displacement of the fibula in relation of the tibia.
measure: Computed tomography in evaluation of the restoration of the normal anatomy
time frame: Before surgery and repated at 0 and 12 weeks
description: CT imaging allows to evaluate the success in fracture reduction and the maintenance of the restored anatomy during the follow-up
measure: Conventional radiographic evaluation
time frame: Before surgery and at 0, 6, 12 and 52 weeks
description: The method is applied to assess fracture reduction and retention, progress of fracture union, possible implant-related osteolysis and posttraumatic arthritis
measure: Systemic exposure to the released antibiotic
time frame: 6 weeks
description: A venous sample for measurement of the serum concentration of ciprofloxacin using the HPLC-FLD method.
measure: Functional recovery after ankle surgery
time frame: Before surgery and at 12 and 52 weeks
description: Clinical examination of the ankle (range of motion, measurement of the circumferences of the calf) and standardized questionnaires (AAOS Foot and Ankle Outcome Instrument, Olerud-Molander Ankle Score, VAS-pain evaluation)
arm group label: Single-arm
arm group type: Experimental
description: The syndesmosis injury of the patients will be fixed with a ciprofloxacin containing bioabsorbable PLGA bone screw or a stainless steel metal screw
intervention type: Procedure
intervention name: A ciprofloxacin containing bioabsorbable PLGA bone screw
description: The syndesmosis injury will be fixed the antibiotic releasing bioabsorbable bone screw or a standard metal screw. After surgery, the ankle will be immobilized in a cast for 6 weeks. The metal screw will be surgically removed at 8 weeks. The bioabsorbable screw will be left in place.
arm group label: Single-arm
other name: Manufactured in Tampere University of Technology/Bioretec Ltd
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Hannu T Aro, MD, PhD
role: Principal Investigator
affiliation: Turku University Hospital
facility: 
country: Finland
url: http://www.orthopaedics.utu.fi
description: Related Info
citation: Makinen TJ, Veiranto M, Knuuti J, Jalava J, Tormala P, Aro HT. Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus. Bone. 2005 Feb;36(2):292-9. doi: 10.1016/j.bone.2004.11.009.
PMID: 15780955
citation: Makinen TJ, Mattila KT, Maattanen H, Aro HT. Comparison of digital and conventional radiostereometric image analysis in an ankle phantom model. Scand J Surg. 2005;94(3):233-8. doi: 10.1177/145749690509400311.
PMID: 16259174
citation: Niemela SM, Ikaheimo I, Koskela M, Veiranto M, Suokas E, Tormala P, Waris T, Ashammakhi N, Syrjala H. Ciprofloxacin-releasing bioabsorbable polymer is superior to titanium in preventing Staphylococcus epidermidis attachment and biofilm formation in vitro. J Biomed Mater Res B Appl Biomater. 2006 Jan;76(1):8-14. doi: 10.1002/jbm.b.30414.
PMID: 16265660
citation: Veiranto M, Tormala P, Suokas E. In vitro mechanical and drug release properties of bioabsorbable ciprofloxacin containing and neat self-reinforced P(L/DL)LA 70/30 fixation screws. J Mater Sci Mater Med. 2002 Dec;13(12):1259-63. doi: 10.1023/a:1021187331458.
PMID: 15348674
responsible party type: Sponsor
mesh term: Fractures, Bone
mesh term: Ankle Fractures
mesh term: Ciprofloxacin