<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/NCT04401553</url>
  </required_header>
  <id_info>
    <org_study_id>STU-2020-0317</org_study_id>
    <nct_id>NCT04401553</nct_id>
  </id_info>
  <brief_title>Prophylactic Antibiotics for Surgical Site Infections and Beta-Lactam Allergy</brief_title>
  <official_title>First Tier Versus Second Tier Antibiotics for Surgical Site Infections Following Hysterectomy In the Patients With a Beta-Lactam Allergy: A Prospective, Randomized, Single-Blinded Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</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>
      Postoperative surgical site infection (SSI) is associated with unnecessary use of heath care&#xD;
      resources including prolonged hospitalization and increased hospital readmission.&#xD;
      Perioperative antibiotic prophylaxis is one of the most important strategies for prevention&#xD;
      of SSI. If there is a beta-lactam allergy, second tier antibiotics (vancomycin and&#xD;
      clindamycin) are recommended alternatives to first- and second-generation cephalosporins&#xD;
      because of fears of possible allergy.&#xD;
&#xD;
      This prospective, randomized, and single-blinded clinical trial is designed to examine&#xD;
      causality between second tier antibiotics use and surgical site infections in the subjects&#xD;
      with a documented unverified penicillin allergy. Unverified beta-lactam allergy could be&#xD;
      associated with antimicrobial treatment failure with second tires antibiotics during&#xD;
      postoperative period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this prospective, randomized, single-blinded clinical trial, eligible subjects will be&#xD;
      identified based on scheduled elective hysterectomy. Subjects with documented beta-lactam&#xD;
      allergy in their chart will be evaluated to differentiate true allergy and allergy-like&#xD;
      events. Subjects with history of allergy-like event to beta-lactam antibiotics will be&#xD;
      randomized to either receive first tier antibiotic or second tier antibiotics before&#xD;
      anesthesia induction.&#xD;
&#xD;
      Preoperative Screening of Allergy The potential subjects' history of allergy will be reviewed&#xD;
      according to described criteria of allergy like events. Subjects with documented anaphylaxis&#xD;
      to first tier and second tier antibiotics will be excluded. Only subjects with a history of&#xD;
      previous allergic-like event after beta-lactam antibiotic will be enrolled to the study.&#xD;
&#xD;
      An allergy self-screening questionnaires will be reviewed before the surgery to identify true&#xD;
      allergy or allergy-like event to beta-lactam (penicillin). Allergic-like events include&#xD;
      nausea, vomiting, feeling dizziness, dermatitis seen after beta-lactam antibiotic, or any&#xD;
      other description of hypersensitivity reactions other than anaphylactic shock, angioedema,&#xD;
      laryngeal spasm, and shock. Administration of the potential confounding drugs such as&#xD;
      antihistamines, systemic and topical corticosteroids and potential confounding diagnosis such&#xD;
      as autoimmune disease will be also reviewed together with allergy history of the subjects to&#xD;
      differentiate true hypersensitivity and allergy-like events to penicillin and other&#xD;
      beta-lactam antibiotics.&#xD;
&#xD;
      Postoperative Follow-up for SSI:&#xD;
&#xD;
      Subjects will be followed postoperatively for post-discharge SSIs or clostridium infection by&#xD;
      reviewing medical records and contacting via phone and survey. If the subject received care&#xD;
      outside the clinic, their provider will be contacted to obtain outside clinic record with&#xD;
      subject permission.&#xD;
&#xD;
      The post-discharge SSIs will be followed according to the SSI surveillance survey protocol&#xD;
      (Harrington et al. 2013). A combination of methods listed below will be used to detect&#xD;
      post-discharge SSI.&#xD;
&#xD;
        1. Identification of subject readmitted with SSI (medical record review)&#xD;
&#xD;
        2. Detection of SSI at outpatient clinic, other return visit to hospital or review by&#xD;
           healthcare staff (direct observation of the wound by health professional)&#xD;
&#xD;
        3. Telephone interviews or questionnaire (self-reported SSI)&#xD;
&#xD;
             -  Early post-operative follow-up (30-days) Subjects will be contacted via phone at 30&#xD;
                days (±3 days) post-operatively to determine if they have been told by a physician&#xD;
                they have a wound infection or if their post-operative antibiotics will extend due&#xD;
                to concern for wound infection.&#xD;
&#xD;
             -  Late post-operative follow-up (90-days) A redcap survey will be sent at&#xD;
                postoperative 90 days to review any possible wound infection.&#xD;
&#xD;
      Surgical Site infection (Wound) Classification Based on standard definitions from the US&#xD;
      Centers for Disease Control and Prevention for SSI, the wound infections will be classified&#xD;
      as&#xD;
&#xD;
        1. superficial incisional (infection occurred within 30 days after any operative procedure&#xD;
           and involved only skin and subcutaneous tissue of the incision),&#xD;
&#xD;
        2. deep incisional primary/secondary (infection occurred within 31-90 days after the&#xD;
           operative procedure and involved deep soft tissues of the incision), or organ/space&#xD;
           (infection occurred within 31-90 days after the operative procedure and involved any&#xD;
           part of the body deeper than the fascia/muscle layers that was opened or manipulated&#xD;
           during the operative procedure.&#xD;
&#xD;
      Criteria of the SSI decision for the female reproductive tract infection (excluding&#xD;
      endometritis or vaginal cuff infections) must meet at least one of the following criteria:&#xD;
&#xD;
        -  Criterion 1: Organisms are cultured from tissue or fluid from affected site.&#xD;
&#xD;
        -  Criterion 2: There is an abscess or other evidence of infection of affected site seen&#xD;
           during a surgical operation or histopathological examination.&#xD;
&#xD;
        -  Criterion 3: The subjects have two of the following signs or symptoms with no other&#xD;
           recognized cause: fever (&gt;38°C), nausea, vomiting, pain, tenderness, or dysuria, and at&#xD;
           least one of the following: (a) organisms cultured from blood (b) diagnosis by&#xD;
           physician.&#xD;
&#xD;
      The SSI criteria listed above will be applied to the self-reported SSI. Type of SSI will not&#xD;
      be recorded in self-reported SSI. Wound type will be decided according to documentation of&#xD;
      clinician who evaluates the wound. If a superficial SSI progresses into a deep SSI, it will&#xD;
      be reported as the deep SSI only. It may be possible for a subject to have an organ/space SSI&#xD;
      in addition to a SSI affecting the incision (superficial or deep) but if more than one SSI is&#xD;
      reported each must meet the case definition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">August 16, 2024</start_date>
  <completion_date type="Anticipated">August 2026</completion_date>
  <primary_completion_date type="Anticipated">August 2026</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 infections during early postoperative period</measure>
    <time_frame>Early post-operative period within a 30-day after hysterectomy</time_frame>
    <description>Incidence of surgical site infections after hysterectomy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Infectious hospital readmission</measure>
    <time_frame>the postoperative period within a 90-days after hysterectomy</time_frame>
    <description>Incidence of infectious hospital readmission</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">240</enrollment>
  <condition>Surgical Site Infection</condition>
  <condition>Beta-lactam Allergy</condition>
  <arm_group>
    <arm_group_label>First Tier Antibiotic</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>First tier antibiotics, cephalosporin, will be given before anesthesia induction in the subjects with a history of allergy-like event to beta-lactam</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Second Tier Antibiotic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Second tier antibiotics, vancomycin, will be given before anesthesia induction for infection prevention in the subjects with a history of allergy-like event to beta-lactam</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>cephalosporin</intervention_name>
    <description>First tier antibiotics, cephalosporin, will be given before anesthesia induction in the subjects with a history of allergy-like event to beta-lactam</description>
    <arm_group_label>First Tier Antibiotic</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Second tier antibiotic (Vancomycin)</intervention_name>
    <description>Second tier antibiotics, vancomycin, will be given before anesthesia induction for infection prevention in the subjects with a history of allergy-like event to beta-lactam (standard of care)</description>
    <arm_group_label>Second Tier Antibiotic</arm_group_label>
    <other_name>Vancomycin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subjects age 18 and older&#xD;
&#xD;
          2. Subjects undergoing open total abdominal hysterectomy&#xD;
&#xD;
          3. Subjects with documented beta-lactam allergy&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with documented anaphylaxis to Tier 1 or Tier 2 antibiotics&#xD;
&#xD;
          2. Surgical procedure within 30 days prior to hysterectomy&#xD;
&#xD;
          3. Robotic hysterectomy&#xD;
&#xD;
          4. Presence of multidrug resistant organism such as methicillin-resistant Staphylococcus&#xD;
             aureus (MRSA)&#xD;
&#xD;
          5. Immunocompromised subject&#xD;
&#xD;
          6. Cognitive deficits 7- Chronic Kidney Disease or patients on dialysis 8- Severe liver&#xD;
             disease&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark Haney, MD</last_name>
    <role>Study Director</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mark Haney, MD</last_name>
    <phone>214-648-6400</phone>
    <email>Mark.Haney@UTSouthwestern.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>James Berry, MD</last_name>
    <phone>214-645-0089</phone>
    <email>James.Berry@UTSouthwestern.edu</email>
  </overall_contact_backup>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>May 20, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>December 1, 2022</last_update_submitted>
  <last_update_submitted_qc>December 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Mark Haney</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <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>
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Vancomycin</mesh_term>
    <mesh_term>Cephalosporins</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/NCT04401553
org study id: STU-2020-0317
nct id: NCT04401553
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Postoperative surgical site infection (SSI) is associated with unnecessary use of heath care
      resources including prolonged hospitalization and increased hospital readmission.
      Perioperative antibiotic prophylaxis is one of the most important strategies for prevention
      of SSI. If there is a beta-lactam allergy, second tier antibiotics (vancomycin and
      clindamycin) are recommended alternatives to first- and second-generation cephalosporins
      because of fears of possible allergy.

      This prospective, randomized, and single-blinded clinical trial is designed to examine
      causality between second tier antibiotics use and surgical site infections in the subjects
      with a documented unverified penicillin allergy. Unverified beta-lactam allergy could be
      associated with antimicrobial treatment failure with second tires antibiotics during
      postoperative period.
In this prospective, randomized, single-blinded clinical trial, eligible subjects will be
      identified based on scheduled elective hysterectomy. Subjects with documented beta-lactam
      allergy in their chart will be evaluated to differentiate true allergy and allergy-like
      events. Subjects with history of allergy-like event to beta-lactam antibiotics will be
      randomized to either receive first tier antibiotic or second tier antibiotics before
      anesthesia induction.

      Preoperative Screening of Allergy The potential subjects' history of allergy will be reviewed
      according to described criteria of allergy like events. Subjects with documented anaphylaxis
      to first tier and second tier antibiotics will be excluded. Only subjects with a history of
      previous allergic-like event after beta-lactam antibiotic will be enrolled to the study.

      An allergy self-screening questionnaires will be reviewed before the surgery to identify true
      allergy or allergy-like event to beta-lactam (penicillin). Allergic-like events include
      nausea, vomiting, feeling dizziness, dermatitis seen after beta-lactam antibiotic, or any
      other description of hypersensitivity reactions other than anaphylactic shock, angioedema,
      laryngeal spasm, and shock. Administration of the potential confounding drugs such as
      antihistamines, systemic and topical corticosteroids and potential confounding diagnosis such
      as autoimmune disease will be also reviewed together with allergy history of the subjects to
      differentiate true hypersensitivity and allergy-like events to penicillin and other
      beta-lactam antibiotics.

      Postoperative Follow-up for SSI:

      Subjects will be followed postoperatively for post-discharge SSIs or clostridium infection by
      reviewing medical records and contacting via phone and survey. If the subject received care
      outside the clinic, their provider will be contacted to obtain outside clinic record with
      subject permission.

      The post-discharge SSIs will be followed according to the SSI surveillance survey protocol
      (Harrington et al. 2013). A combination of methods listed below will be used to detect
      post-discharge SSI.

        1. Identification of subject readmitted with SSI (medical record review)

        2. Detection of SSI at outpatient clinic, other return visit to hospital or review by
           healthcare staff (direct observation of the wound by health professional)

        3. Telephone interviews or questionnaire (self-reported SSI)

             -  Early post-operative follow-up (30-days) Subjects will be contacted via phone at 30
                days (±3 days) post-operatively to determine if they have been told by a physician
                they have a wound infection or if their post-operative antibiotics will extend due
                to concern for wound infection.

             -  Late post-operative follow-up (90-days) A redcap survey will be sent at
                postoperative 90 days to review any possible wound infection.

      Surgical Site infection (Wound) Classification Based on standard definitions from the US
      Centers for Disease Control and Prevention for SSI, the wound infections will be classified
      as

        1. superficial incisional (infection occurred within 30 days after any operative procedure
           and involved only skin and subcutaneous tissue of the incision),

        2. deep incisional primary/secondary (infection occurred within 31-90 days after the
           operative procedure and involved deep soft tissues of the incision), or organ/space
           (infection occurred within 31-90 days after the operative procedure and involved any
           part of the body deeper than the fascia/muscle layers that was opened or manipulated
           during the operative procedure.

      Criteria of the SSI decision for the female reproductive tract infection (excluding
      endometritis or vaginal cuff infections) must meet at least one of the following criteria:

        -  Criterion 1: Organisms are cultured from tissue or fluid from affected site.

        -  Criterion 2: There is an abscess or other evidence of infection of affected site seen
           during a surgical operation or histopathological examination.

        -  Criterion 3: The subjects have two of the following signs or symptoms with no other
           recognized cause: fever (>38°C), nausea, vomiting, pain, tenderness, or dysuria, and at
           least one of the following: (a) organisms cultured from blood (b) diagnosis by
           physician.

      The SSI criteria listed above will be applied to the self-reported SSI. Type of SSI will not
      be recorded in self-reported SSI. Wound type will be decided according to documentation of
      clinician who evaluates the wound. If a superficial SSI progresses into a deep SSI, it will
      be reported as the deep SSI only. It may be possible for a subject to have an organ/space SSI
      in addition to a SSI affecting the incision (superficial or deep) but if more than one SSI is
      reported each must meet the case definition.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Surgical site infections during early postoperative period
time frame: Early post-operative period within a 30-day after hysterectomy
description: Incidence of surgical site infections after hysterectomy
measure: Infectious hospital readmission
time frame: the postoperative period within a 90-days after hysterectomy
description: Incidence of infectious hospital readmission
arm group label: First Tier Antibiotic
arm group type: Experimental
description: First tier antibiotics, cephalosporin, will be given before anesthesia induction in the subjects with a history of allergy-like event to beta-lactam
arm group label: Second Tier Antibiotic
arm group type: Active Comparator
description: Second tier antibiotics, vancomycin, will be given before anesthesia induction for infection prevention in the subjects with a history of allergy-like event to beta-lactam
intervention type: Drug
intervention name: cephalosporin
description: First tier antibiotics, cephalosporin, will be given before anesthesia induction in the subjects with a history of allergy-like event to beta-lactam
arm group label: First Tier Antibiotic
intervention type: Drug
intervention name: Second tier antibiotic (Vancomycin)
description: Second tier antibiotics, vancomycin, will be given before anesthesia induction for infection prevention in the subjects with a history of allergy-like event to beta-lactam (standard of care)
arm group label: Second Tier Antibiotic
other name: Vancomycin
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Mark Haney, MD
role: Study Director
affiliation: UT Southwestern Medical Center
last name: Mark Haney, MD
phone: 214-648-6400
email: Mark.Haney@UTSouthwestern.edu
last name: James Berry, MD
phone: 214-645-0089
email: James.Berry@UTSouthwestern.edu
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Mark Haney
investigator title: Assistant Professor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Surgical Wound Infection
mesh term: Hypersensitivity
mesh term: Anti-Bacterial Agents
mesh term: Vancomycin
mesh term: Cephalosporins