<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/NCT03308253</url>
  </required_header>
  <id_info>
    <org_study_id>Antimicrobial Beads</org_study_id>
    <nct_id>NCT03308253</nct_id>
  </id_info>
  <brief_title>Study for Antibiotic Impregnated Calcium Sulfate Beads as Prophylaxis for Surgical Site Infection</brief_title>
  <official_title>Pilot Study for Antibiotic Impregnated Calcium Sulfate Beads as Prophylaxis for Surgical Site Infection in Vascular Surgery Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McMaster University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The CDC quotes a rate of wound infection of 2-5% for inpatient surgery. Patients undergoing a&#xD;
      vascular operation, however, are generally at an increased risk of wound infection with rates&#xD;
      often close to 5-10%. Groin incisions are an additional risk factor for surgical site&#xD;
      infections, with rates of wound infection being quoted from 10-15%, and even as high as 30%&#xD;
      in high risk patients. The use of implantable calcium sulfate beads mixed with antibiotics&#xD;
      may help to lower the rate of infection in these high risk patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The initial pilot will consist of 30 patients per arm and will provide estimates of effect&#xD;
      size, event rates, and recruitment rates. It will mirror the final study in terms of&#xD;
      methodology. This will occur at the Hamilton General Hospital (Hamilton, ON. Canada)&#xD;
&#xD;
      Patients will be randomized to either the exposure group or control group by the study&#xD;
      coordinator. Patients will be block randomized among surgeons (6), so that each surgeon has&#xD;
      an equal number of patients in the control and exposure arms. Randomization will occur once&#xD;
      an operative date has been booked for a patient. The arm they are assigned to will be how the&#xD;
      patient is treated, regardless of if they are cancelled and re-booked. Should patients be&#xD;
      done as an emergency procedure, prior to their index procedure (when the beads would be&#xD;
      implanted), they will be excluded from the study. As no intervention has occurred at this&#xD;
      point, there will be no informative loss to follow-up or censoring and therefore this will&#xD;
      not impact validity of the design. We are unable to provide beads for emergency procedures,&#xD;
      as the research pharmacy is not open.&#xD;
&#xD;
      The research coordinator will inform the research pharmacy to produce calcium sulfate beads&#xD;
      impregnated with Vancomycin (1g) and Tobramycin (240mg) for the exposure arm. The control arm&#xD;
      will receive standard care. The only difference between standard care and the treatment arm&#xD;
      is the use of the antibiotic calcium sulfate beads. Beads will be delivered in a sterile&#xD;
      manner to the OR. For each patient half of a standard 10cc kit will be delivered (5cc of&#xD;
      Stimulan Calcium Sulfate). As the beads are being applied only to a groin incision(s) this&#xD;
      will provide an adequate volume of beads. It will also prevent insertion of excess beads.&#xD;
&#xD;
      Surgeons will insert the beads loosely within the soft tissue of groin incisions, so as not&#xD;
      to distort the normal anatomy. This technique will be discussed with all surgeons prior to&#xD;
      pilot initiation as a group. This will aim to standardize the method among involved surgeons.&#xD;
      At the end of the study we will complete a focus group with surgeons to discuss their&#xD;
      experience using the beads to better inform the protocol for the final RCT. Patients are&#xD;
      randomized as a unit and therefore, if there are bilateral groin incisions, both will be&#xD;
      treated as per their randomization.&#xD;
&#xD;
      Patients will be blinded to which treatment they receive. The beads are believed to be&#xD;
      non-detectable to the patient. Only by means of wound dehiscence would a patient be expected&#xD;
      to determine their treatment group. For practical reasons the surgeon cannot be blinded to&#xD;
      treatment. Nurse assessors and study authors conducting review of patient records will be&#xD;
      blinded to patient treatment.&#xD;
&#xD;
      Patients will be recruited from all patients consented for an included procedure at HGH. A&#xD;
      study coordinator or a resident will obtain consent. The patient's primary physician will not&#xD;
      be involved in the consent process.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 16, 2018</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">June 2019</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Surgical Site Infection</measure>
    <time_frame>30 days</time_frame>
    <description>The primary outcome will be combined, superficial, deep or organ/space infection as defined by the CDC. The CDC definition for surgical site infection is one of the most widely used and is both the NSQUIP and NHSN definition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Wound Complication Rate</measure>
    <time_frame>30 day</time_frame>
    <description>Wound complications will be defined as: wound dehiscence, skin edge necrosis, hematoma, seroma, increased wound exudate, graft exposure. These will be measured with a standardized form, by the blinded nurse assessor, at each follow-up appointment. They will additionally be assessed by the author reviewing patient records at thirty days. If imaging is required for diagnosis of hematoma or seroma, the result will be collected from the imaging records, and treated as consistent with the conclusions of the formal imaging report.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Surgical Graft Infection Rate</measure>
    <time_frame>90 day</time_frame>
    <description>Graft infection is defined as; diagnosis by surgeon or surgical designate requiring re-operation or prolonged course of antibiotic therapy. An author blinded to patient treatment will review the records of the patient including patient charts, antibiotic prescriptions, home care and ID referrals and record the information in a standardized form for this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bacterial Resistance</measure>
    <time_frame>30 day</time_frame>
    <description>In the event of infection requiring laboratory samples, screening for resistant bacteria will be performed. Bacterial cultures will be performed in order to determine the presence of tobramycin or vancomycin resistant strains.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Surgical Site Infection</condition>
  <arm_group>
    <arm_group_label>Standard of Care</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients will receive the standard of care for vascular procedures as it is provided at Hamilton General Hospital</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antibiotic Impregnated Beads</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will have their wound packed with calcium sulfate beads prior to closing. The beads will be infused with the antibiotics vancomycin and tobramycin.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Stimulan Rapid Cure</intervention_name>
    <description>Calcium sulfate dissolvable beads</description>
    <arm_group_label>Antibiotic Impregnated Beads</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vancomycin</intervention_name>
    <description>0.5 g Vancomycin per patient</description>
    <arm_group_label>Antibiotic Impregnated Beads</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tobramycin</intervention_name>
    <description>120 mg tobramycin per patient</description>
    <arm_group_label>Antibiotic Impregnated Beads</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>Standard of care provided at Hamilton General Hospital consisting of dressings for the wound.</description>
    <arm_group_label>Standard of Care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women aged &gt; 18&#xD;
&#xD;
          -  Undergoing a revascularization procedure involving the femoral artery and requiring&#xD;
             either unilateral or bilateral groin incision&#xD;
&#xD;
          -  BMI &gt; 30&#xD;
&#xD;
          -  Presence of one of the following: current smoker, diabetes requiring pharmacologic&#xD;
             intervention, previous re-vascularization procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any patient with a current infection or requiring ongoing use of antibiotics&#xD;
&#xD;
          -  Any patient who otherwise has an indication requiring the use of antibiotic&#xD;
             impregnated material&#xD;
&#xD;
          -  Known allergy or sensitivity to tobramycin or vancomycin&#xD;
&#xD;
          -  Grade 4 or 5 chronic kidney disease&#xD;
&#xD;
          -  Moderate or severe hypercalcemia&#xD;
&#xD;
          -  Any woman currently pregnant or planning on becoming pregnant during the course of the&#xD;
             study&#xD;
&#xD;
          -  Any patient involved in another study that, in the investigators opinion, is believed&#xD;
             will interfere with the study&#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>Michael C Stacey, DS</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Steven Phillips, MSc</last_name>
    <phone>905-521-2100</phone>
    <phone_ext>44167</phone_ext>
    <email>phills3@mcmaster.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Hamilton General Hospital</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 2X2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Steven Phillips, MSc</last_name>
      <phone>905-521-2100</phone>
      <phone_ext>44167</phone_ext>
      <email>phills3@mcmaster.ca</email>
    </contact>
    <investigator>
      <last_name>Michael C Stacey</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Brandon McGuinness</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>October 3, 2017</study_first_submitted>
  <study_first_submitted_qc>October 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 12, 2017</study_first_posted>
  <last_update_submitted>July 17, 2018</last_update_submitted>
  <last_update_submitted_qc>July 17, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 19, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vascular Surgery</keyword>
  <keyword>Surgical Site Infection</keyword>
  <keyword>Prophylactic Antibiotics</keyword>
  <keyword>Implantable Beads</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Infections</mesh_term>
    <mesh_term>Communicable Diseases</mesh_term>
    <mesh_term>Surgical Wound Infection</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vancomycin</mesh_term>
    <mesh_term>Tobramycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Individual patient data will not be shared for this pilot study.</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/NCT03308253
org study id: Antimicrobial Beads
nct id: NCT03308253
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
The CDC quotes a rate of wound infection of 2-5% for inpatient surgery. Patients undergoing a
      vascular operation, however, are generally at an increased risk of wound infection with rates
      often close to 5-10%. Groin incisions are an additional risk factor for surgical site
      infections, with rates of wound infection being quoted from 10-15%, and even as high as 30%
      in high risk patients. The use of implantable calcium sulfate beads mixed with antibiotics
      may help to lower the rate of infection in these high risk patients.
The initial pilot will consist of 30 patients per arm and will provide estimates of effect
      size, event rates, and recruitment rates. It will mirror the final study in terms of
      methodology. This will occur at the Hamilton General Hospital (Hamilton, ON. Canada)

      Patients will be randomized to either the exposure group or control group by the study
      coordinator. Patients will be block randomized among surgeons (6), so that each surgeon has
      an equal number of patients in the control and exposure arms. Randomization will occur once
      an operative date has been booked for a patient. The arm they are assigned to will be how the
      patient is treated, regardless of if they are cancelled and re-booked. Should patients be
      done as an emergency procedure, prior to their index procedure (when the beads would be
      implanted), they will be excluded from the study. As no intervention has occurred at this
      point, there will be no informative loss to follow-up or censoring and therefore this will
      not impact validity of the design. We are unable to provide beads for emergency procedures,
      as the research pharmacy is not open.

      The research coordinator will inform the research pharmacy to produce calcium sulfate beads
      impregnated with Vancomycin (1g) and Tobramycin (240mg) for the exposure arm. The control arm
      will receive standard care. The only difference between standard care and the treatment arm
      is the use of the antibiotic calcium sulfate beads. Beads will be delivered in a sterile
      manner to the OR. For each patient half of a standard 10cc kit will be delivered (5cc of
      Stimulan Calcium Sulfate). As the beads are being applied only to a groin incision(s) this
      will provide an adequate volume of beads. It will also prevent insertion of excess beads.

      Surgeons will insert the beads loosely within the soft tissue of groin incisions, so as not
      to distort the normal anatomy. This technique will be discussed with all surgeons prior to
      pilot initiation as a group. This will aim to standardize the method among involved surgeons.
      At the end of the study we will complete a focus group with surgeons to discuss their
      experience using the beads to better inform the protocol for the final RCT. Patients are
      randomized as a unit and therefore, if there are bilateral groin incisions, both will be
      treated as per their randomization.

      Patients will be blinded to which treatment they receive. The beads are believed to be
      non-detectable to the patient. Only by means of wound dehiscence would a patient be expected
      to determine their treatment group. For practical reasons the surgeon cannot be blinded to
      treatment. Nurse assessors and study authors conducting review of patient records will be
      blinded to patient treatment.

      Patients will be recruited from all patients consented for an included procedure at HGH. A
      study coordinator or a resident will obtain consent. The patient's primary physician will not
      be involved in the consent process.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Surgical Site Infection
time frame: 30 days
description: The primary outcome will be combined, superficial, deep or organ/space infection as defined by the CDC. The CDC definition for surgical site infection is one of the most widely used and is both the NSQUIP and NHSN definition.
measure: Wound Complication Rate
time frame: 30 day
description: Wound complications will be defined as: wound dehiscence, skin edge necrosis, hematoma, seroma, increased wound exudate, graft exposure. These will be measured with a standardized form, by the blinded nurse assessor, at each follow-up appointment. They will additionally be assessed by the author reviewing patient records at thirty days. If imaging is required for diagnosis of hematoma or seroma, the result will be collected from the imaging records, and treated as consistent with the conclusions of the formal imaging report.
measure: Surgical Graft Infection Rate
time frame: 90 day
description: Graft infection is defined as; diagnosis by surgeon or surgical designate requiring re-operation or prolonged course of antibiotic therapy. An author blinded to patient treatment will review the records of the patient including patient charts, antibiotic prescriptions, home care and ID referrals and record the information in a standardized form for this endpoint.
measure: Bacterial Resistance
time frame: 30 day
description: In the event of infection requiring laboratory samples, screening for resistant bacteria will be performed. Bacterial cultures will be performed in order to determine the presence of tobramycin or vancomycin resistant strains.
arm group label: Standard of Care
arm group type: Other
description: Patients will receive the standard of care for vascular procedures as it is provided at Hamilton General Hospital
arm group label: Antibiotic Impregnated Beads
arm group type: Experimental
description: Patients will have their wound packed with calcium sulfate beads prior to closing. The beads will be infused with the antibiotics vancomycin and tobramycin.
intervention type: Device
intervention name: Stimulan Rapid Cure
description: Calcium sulfate dissolvable beads
arm group label: Antibiotic Impregnated Beads
intervention type: Drug
intervention name: Vancomycin
description: 0.5 g Vancomycin per patient
arm group label: Antibiotic Impregnated Beads
intervention type: Drug
intervention name: Tobramycin
description: 120 mg tobramycin per patient
arm group label: Antibiotic Impregnated Beads
intervention type: Other
intervention name: Standard of Care
description: Standard of care provided at Hamilton General Hospital consisting of dressings for the wound.
arm group label: Standard of Care
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael C Stacey, DS
role: Principal Investigator
affiliation: McMaster University
last name: Steven Phillips, MSc
phone: 905-521-2100
phone ext: 44167
email: phills3@mcmaster.ca
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Canada
responsible party type: Sponsor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection
mesh term: Vancomycin
mesh term: Tobramycin
sharing ipd: No
ipd description: Individual patient data will not be shared for this pilot study.