xml: <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/NCT05964140</url>
    </required_header>
    <id_info>
      <org_study_id>DEV008</org_study_id>
      <nct_id>NCT05964140</nct_id>
    </id_info>
    <brief_title>The MANTRA Trial (MANdibular TRauma and Antibiotic Use)</brief_title>
    <acronym>MANTRA</acronym>
    <official_title>Should we Use Post-operative Antibiotics to Prevent Surgical Site Infections (SSIs) Following Surgery for Patients With Mandible Fractures? The MANTRA Trial - a Phase III, Non-inferiority, Non-blinded, Pragmatic Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>East Lancashire Hospitals NHS Trust</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>East Lancashire Hospitals NHS Trust</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>
        1. FULL TITLE OF THE PROJECT Should we use post-operative antibiotics following surgery for&#xD;
             patients with mandible fractures? The MANTRA trial (MANdibular TRauma and Antibiotic&#xD;
             use)&#xD;
  &#xD;
          2. SUMMARY OF RESEARCH (ABSTRACT) Research Question: Are post-operative antibiotics&#xD;
             required following surgery for patients with mandible fractures? Background: Mandible&#xD;
             fractures are the commonest facial fractures needing surgery and account for a&#xD;
             significant percentage of the acute workload in Oral &amp; Maxillofacial Surgery (OMFS)&#xD;
             units. The UK records over 6000 new cases per year. Patients having surgery for mandible&#xD;
             fractures have a theoretical risk of developing surgical site infection, due to the&#xD;
             proximity of the fracture lines to the oral cavity microbes and the presence of foreign&#xD;
             body (titanium fixation miniplates). For this reason, clinicians often prescribe&#xD;
             antibiotics after surgery, to reduce the risk of infection. Previous systematic reviews&#xD;
             and a multicentre cohort study performed by this team, revealed significant clinical&#xD;
             variation in post-operative antibiotic prescription amongst UK OMFS clinicians and the&#xD;
             presence of clinical equipoise. Antibiotic overuse can lead to antibiotic resistance and&#xD;
             other antibiotic-related side effects; judicious antibiotic use and stewardship is of&#xD;
             paramount importance.&#xD;
  &#xD;
        Aim: To determine whether post-operative antibiotics are required at all, following surgery&#xD;
        for mandible fractures, and, if so, what is the most clinically- and cost-effective regimen&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective To conduct a Randomized Controlled Trial (MANTRA) in order to establish the&#xD;
        non-inferiority (or not) of not giving post-operative antibiotics versus 2 other&#xD;
        post-operative antibiotic regimens. An internal pilot phase will optimise recruitment and&#xD;
        retention.&#xD;
  &#xD;
        Secondary Objectives&#xD;
  &#xD;
          -  Measure the cost-effectiveness of the proposed antibiotic pathways&#xD;
  &#xD;
          -  Assess patient and clinician acceptability to change clinical practice&#xD;
  &#xD;
          -  Process evaluation to inform dissemination and implementation Methods: The investigators&#xD;
             designed and propose the MANTRA RCT to compare 3 post-operative antibiotic approaches to&#xD;
             prevent Surgical Site Infections (SSIs) following surgery for mandible fractures. The&#xD;
             MANTRA trial is a large open label, multicentre study in NHS OMFS units. The 3 study&#xD;
             arms represent the most common clinical pathways in the UK based on previous work; the&#xD;
             control group is the approach prescribed by most UK OMFS clinicians. All patients will&#xD;
             receive 1 dose of IV antibiotics (co-amoxiclav 1.2g, if no penicillin allergy, which is&#xD;
             the most commonly used prophylactic antibiotic currently) on induction of anaesthesia,&#xD;
             prior to their surgery.&#xD;
  &#xD;
        The participants will be randomised to the following (1:1:1):&#xD;
  &#xD;
        Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav&#xD;
        1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral&#xD;
        co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control).&#xD;
  &#xD;
        Trial processes will be optimised by an internal pilot phase ensuring we recruit, randomise,&#xD;
        and retain participants with clear progression criteria. We will also conduct&#xD;
        cost-effectiveness analyses and process evaluation for dissemination and implementation&#xD;
  &#xD;
        Timeline:&#xD;
  &#xD;
        Start of grant: 1st July 2023 Start of RCT / pilot: 1st January 2024 End of pilot: 30th June&#xD;
        2024 End of recruitment: 31st December 2026 End of follow-up: 30th June 2027 Completion: 31st&#xD;
        December 2027&#xD;
  &#xD;
        Impact and dissemination:&#xD;
  &#xD;
          -  Practice changing outputs that standardise the use of antibiotics in mandible fractures&#xD;
             in the NHS and provide a framework for other surgical prophylaxis research&#xD;
  &#xD;
          -  A bespoke clinical dissemination plan via an engagement and training legacy&#xD;
  &#xD;
          -  Cost-effectiveness data to inform policy making&#xD;
  &#xD;
          -  A research legacy and change of culture in the specialty of OMFS&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">December 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2027</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Non-inferiority RCT</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Surgical Site Infection</measure>
      <time_frame>30 days</time_frame>
      <description>Incidence of Surgical Site Infection (CDC definition) following surgery for mandible fractures</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Return to theatre within 30 days</measure>
      <time_frame>30 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Length of hospital stay</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Death and cause of death</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Hospital readmission</measure>
      <time_frame>30 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Malunion: fracture non-healing</measure>
      <time_frame>180 days</time_frame>
      <description>Fibrous union, fracture mobility, absence of callus formation</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Malocclusion: teeth not meeting as they should</measure>
      <time_frame>180 days</time_frame>
      <description>When the fracture reduction failed to restore the dental occlusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Metalwork removal</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
      <description>When the fixation titanium miniplates need to be removed at any point and for any reason</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall antibiotic exposure</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Antibiotic related adverse events/serious adverse events</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cost</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>HRQoL (EQ-5D-5L)</measure>
      <time_frame>14 days, 30 days, 180 days</time_frame>
      <description>Health Related Quality of Life</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">2907</enrollment>
    <condition>Mandible Fracture</condition>
    <condition>Post-operative Antibiotics</condition>
    <arm_group>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group A: One induction IV dose</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group B</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Group B: One induction IV dose and 2 further postoperative IV doses</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group C</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Group C: One IV dose of antibiotics on induction and 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Different post-operative antibiotic regimens following surgical treatment of mandible fractures</intervention_name>
      <description>The 3 study arms represent the most common antibiotic regimens used in current clinical practice following surgery for mandible fractures. The control group is the most common approach.&#xD;
  All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g), if no penicillin allergy, on induction of anaesthesia, prior to their surgery.&#xD;
  The participants will be randomised to the following (1:1:1):&#xD;
  Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav 1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control).</description>
      <arm_group_label>Group A</arm_group_label>
      <arm_group_label>Group B</arm_group_label>
      <arm_group_label>Group C</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          All adult patients aged 18 years or over with mandible fractures requiring surgery. Most of&#xD;
          these patients will be identified from the A&amp;E department via the on-call OMFS team or seen&#xD;
          in dedicated OMFS trauma clinics. A small proportion of our study population will be seen&#xD;
          in an OMFS clinic following referral from GP/GDP.&#xD;
  &#xD;
          Inclusion Criteria:&#xD;
  &#xD;
            -  Ability to provide written informed consent&#xD;
  &#xD;
            -  Age≥18 years&#xD;
  &#xD;
            -  Hospital episode of mandible fracture(s)&#xD;
  &#xD;
            -  Planned treatment is surgery - (ORIF with titanium miniplates)&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Isolated mandibular condylar fractures&#xD;
  &#xD;
            -  Existing fracture site infection&#xD;
  &#xD;
            -  Immunocompromised (transplant patients, haematological malignancies, HIV/AIDS) - a&#xD;
               clear definition will be provided in the protocol&#xD;
  &#xD;
            -  Pathological fracture (e.g., malignancy, osteoradionecrosis, cysts, Medication-Related&#xD;
               Osteonecrosis of the Jaws [MRONJ])&#xD;
  &#xD;
            -  Fractures open to skin&#xD;
  &#xD;
            -  Inability to provide written informed consent&#xD;
  &#xD;
            -  Other injuries or infections mandating ongoing post-operative antibiotics (e.g.,&#xD;
               panfacial fractures with mandible fracture component)&#xD;
  &#xD;
            -  Patients allergic to first and second-line antibiotic prophylaxis (as outlined above)&#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>Panayiotis Kyzas, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Consultant OMFS H&amp;N Surgeon ELHT</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Panayiotis Kyzas</last_name>
      <phone>+447505402640</phone>
      <email>Panayiotis.Kyzas@elht.nhs.uk</email>
    </overall_contact>
    <location>
      <facility>
        <name>East Lancashire Hospitals NHS Trust</name>
        <address>
          <city>Oldham</city>
          <state>Greater Manchester</state>
          <zip>OL28HS</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Panayiotis Kyzas</last_name>
        <phone>07505402640</phone>
        <email>Panayiotis.Kyzas@elht.nhs.uk</email>
      </contact>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>July 19, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 19, 2023</last_update_submitted>
    <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Mandible fractures</keyword>
    <keyword>Antibiotics</keyword>
    <keyword>Open Reduction and Internal Fixation</keyword>
    <keyword>Co-amoxiclav</keyword>
    <keyword>Antibiotic Resistance</keyword>
    <keyword>Surgical Site Infection</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mandibular Fractures</mesh_term>
      <mesh_term>Fractures, Bone</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Anti-Bacterial Agents</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05964140
  org study id: DEV008
  nct id: NCT05964140
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  1. FULL TITLE OF THE PROJECT Should we use post-operative antibiotics following surgery for
             patients with mandible fractures? The MANTRA trial (MANdibular TRauma and Antibiotic
             use)
  
          2. SUMMARY OF RESEARCH (ABSTRACT) Research Question: Are post-operative antibiotics
             required following surgery for patients with mandible fractures? Background: Mandible
             fractures are the commonest facial fractures needing surgery and account for a
             significant percentage of the acute workload in Oral & Maxillofacial Surgery (OMFS)
             units. The UK records over 6000 new cases per year. Patients having surgery for mandible
             fractures have a theoretical risk of developing surgical site infection, due to the
             proximity of the fracture lines to the oral cavity microbes and the presence of foreign
             body (titanium fixation miniplates). For this reason, clinicians often prescribe
             antibiotics after surgery, to reduce the risk of infection. Previous systematic reviews
             and a multicentre cohort study performed by this team, revealed significant clinical
             variation in post-operative antibiotic prescription amongst UK OMFS clinicians and the
             presence of clinical equipoise. Antibiotic overuse can lead to antibiotic resistance and
             other antibiotic-related side effects; judicious antibiotic use and stewardship is of
             paramount importance.
  
        Aim: To determine whether post-operative antibiotics are required at all, following surgery
        for mandible fractures, and, if so, what is the most clinically- and cost-effective regimen
  
        Objectives:
  
        Primary Objective To conduct a Randomized Controlled Trial (MANTRA) in order to establish the
        non-inferiority (or not) of not giving post-operative antibiotics versus 2 other
        post-operative antibiotic regimens. An internal pilot phase will optimise recruitment and
        retention.
  
        Secondary Objectives
  
          -  Measure the cost-effectiveness of the proposed antibiotic pathways
  
          -  Assess patient and clinician acceptability to change clinical practice
  
          -  Process evaluation to inform dissemination and implementation Methods: The investigators
             designed and propose the MANTRA RCT to compare 3 post-operative antibiotic approaches to
             prevent Surgical Site Infections (SSIs) following surgery for mandible fractures. The
             MANTRA trial is a large open label, multicentre study in NHS OMFS units. The 3 study
             arms represent the most common clinical pathways in the UK based on previous work; the
             control group is the approach prescribed by most UK OMFS clinicians. All patients will
             receive 1 dose of IV antibiotics (co-amoxiclav 1.2g, if no penicillin allergy, which is
             the most commonly used prophylactic antibiotic currently) on induction of anaesthesia,
             prior to their surgery.
  
        The participants will be randomised to the following (1:1:1):
  
        Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav
        1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral
        co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control).
  
        Trial processes will be optimised by an internal pilot phase ensuring we recruit, randomise,
        and retain participants with clear progression criteria. We will also conduct
        cost-effectiveness analyses and process evaluation for dissemination and implementation
  
        Timeline:
  
        Start of grant: 1st July 2023 Start of RCT / pilot: 1st January 2024 End of pilot: 30th June
        2024 End of recruitment: 31st December 2026 End of follow-up: 30th June 2027 Completion: 31st
        December 2027
  
        Impact and dissemination:
  
          -  Practice changing outputs that standardise the use of antibiotics in mandible fractures
             in the NHS and provide a framework for other surgical prophylaxis research
  
          -  A bespoke clinical dissemination plan via an engagement and training legacy
  
          -  Cost-effectiveness data to inform policy making
  
          -  A research legacy and change of culture in the specialty of OMFS
  allocation: Randomized
  intervention model: Single Group Assignment
  intervention model description: Non-inferiority RCT
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Surgical Site Infection
  time frame: 30 days
  description: Incidence of Surgical Site Infection (CDC definition) following surgery for mandible fractures
  measure: Return to theatre within 30 days
  time frame: 30 days
  measure: Length of hospital stay
  time frame: 14 days, 30 days, 180 days
  measure: Death and cause of death
  time frame: 14 days, 30 days, 180 days
  measure: Hospital readmission
  time frame: 30 days
  measure: Malunion: fracture non-healing
  time frame: 180 days
  description: Fibrous union, fracture mobility, absence of callus formation
  measure: Malocclusion: teeth not meeting as they should
  time frame: 180 days
  description: When the fracture reduction failed to restore the dental occlusion
  measure: Metalwork removal
  time frame: 14 days, 30 days, 180 days
  description: When the fixation titanium miniplates need to be removed at any point and for any reason
  measure: Overall antibiotic exposure
  time frame: 14 days, 30 days, 180 days
  measure: Antibiotic related adverse events/serious adverse events
  time frame: 14 days, 30 days, 180 days
  measure: Cost
  time frame: 14 days, 30 days, 180 days
  measure: HRQoL (EQ-5D-5L)
  time frame: 14 days, 30 days, 180 days
  description: Health Related Quality of Life
  arm group label: Group A
  arm group type: Experimental
  description: Group A: One induction IV dose
  arm group label: Group B
  arm group type: Experimental
  description: Group B: One induction IV dose and 2 further postoperative IV doses
  arm group label: Group C
  arm group type: Active Comparator
  description: Group C: One IV dose of antibiotics on induction and 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy
  intervention type: Drug
  intervention name: Different post-operative antibiotic regimens following surgical treatment of mandible fractures
  description: The 3 study arms represent the most common antibiotic regimens used in current clinical practice following surgery for mandible fractures. The control group is the most common approach.
  All patients will receive 1 dose of IV antibiotics (co-amoxiclav 1.2g), if no penicillin allergy, on induction of anaesthesia, prior to their surgery.
  The participants will be randomised to the following (1:1:1):
  Group A: No further antibiotics Group B: 2 further postoperative IV doses of co-amoxiclav 1.2g Group C: 2 further postoperative IV doses (as above), followed by a 5-day course of oral co-amoxiclav 625mg every 8 hours if no penicillin allergy (Control).
  arm group label: Group A
  arm group label: Group B
  arm group label: Group C
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Panayiotis Kyzas, PhD
  role: Principal Investigator
  affiliation: Consultant OMFS H&N Surgeon ELHT
  last name: Panayiotis Kyzas
  phone: +447505402640
  email: Panayiotis.Kyzas@elht.nhs.uk
  facility: 
  contact: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Mandibular Fractures
  mesh term: Fractures, Bone
  mesh term: Anti-Bacterial Agents