<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/NCT03265834</url>
  </required_header>
  <id_info>
    <org_study_id>MB16/156</org_study_id>
    <nct_id>NCT03265834</nct_id>
  </id_info>
  <brief_title>CABI: Antibiotic Duration for Complicated Intra-ABdominal Infection</brief_title>
  <acronym>CABI</acronym>
  <official_title>The CABI Trial: An Unblinded Parallel Group Randomised Controlled Feasibility Trial of Long Course Antibiotic Therapy (28 Days) Compared to Short Course (≤10 Days) in the Prevention of Complicated Intra-ABdominal Infection Relapses in Adults Treated for Complicated Intra-ABdominal Infection</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Leeds</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Leeds Teaching Hospitals NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Leeds</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Complicated intra-ABdominal Infections (CABIs) are abdominal infections where there is an&#xD;
      abscess inside the abdomen, or a hole (perforation) in an abdominal organ such that infected&#xD;
      material e.g. faeces, leaks into the abdominal cavity. A recent review of CABIs after gut&#xD;
      surgery found that they can occur in several ways. They can occur in different parts of the&#xD;
      abdomen, can be different sizes, and may or may not be caused by a perforated bowel.&#xD;
      Management includes, where possible, surgical drainage of an abscess or treatment of the&#xD;
      damaged bowel. In addition, all patients are given antibiotic therapy. Despite the varied&#xD;
      ways that CABIs occur, we currently tend to treat all CABIs with antibiotics in a similar&#xD;
      way. CABIs are associated with significant morbidity and mortality. Despite a significant&#xD;
      amount of disease there is little clinical evidence with which to base treatment on. One&#xD;
      research study evaluated a short course of antibiotics (4 days) compared with a longer course&#xD;
      (up to 10 days) in combination with surgical removal of infection. There was little&#xD;
      difference in outcomes, but in both groups about 1 out of every 7 patients had a relapse. A&#xD;
      recent review of patients with CABI in Leeds, not in a research study and where surgical&#xD;
      removal infection is uncommon and antibiotic durations were short, showed that the risk of&#xD;
      relapse was even higher (about 1 in every 3 patients). The antibiotic management of CABIs in&#xD;
      the UK is variable and involves giving between 4 days to 28 days of antibiotics.&#xD;
&#xD;
      In summary, there is an unacceptably high relapse rate in patients treated for CABI, and&#xD;
      uncertainty about the best length of antibiotic therapy that should be used to prevent these&#xD;
      relapses. We therefore propose to investigate if long course antibiotic therapy (28 days) is&#xD;
      more effective than short course antibiotics (≤10 days) in preventing relapses of CABI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Complicated intra-abdominal infection (CABI) extends beyond the hollow viscus of origin into&#xD;
      the peritoneal space and is associated with either abscess formation or peritonitis [Solomkin&#xD;
      2010]. CABIs are heterogeneous in aetiology and include spontaneous infections arising from a&#xD;
      perforated viscus, including the stomach, biliary tree, colon, appendix and reproductive&#xD;
      organs. In addition there are post-operative complications such as peritonitis, abscess, and&#xD;
      failure of surgical anastomoses. CABIs are also heterogeneous in their characteristics. A&#xD;
      recent review of organ space Surgical Site Infections (SSI-Os) after colorectal surgery&#xD;
      demonstrated that infections were varied with regard their location, as well as size and&#xD;
      number and nature of collections, and presence of an ongoing source e.g. anastomotic&#xD;
      breakdown (Rothwell 2016). Despite the varied origin of these infections, there are similar&#xD;
      management strategies which centre on the source control, e.g. drainage of intra-abdominal&#xD;
      fluid collections, and administration of antibiotic therapy. CABIs are a common in-hospital&#xD;
      clinical challenge, in part due to the varied pathology they are caused by, and are&#xD;
      associated with significant morbidity and mortality (DeFrances 2005, Brun-Buisson 1995).&#xD;
      Despite this burden of disease, there is little clinical evidence with which to base&#xD;
      treatment on, even before taking account of their heterogeneous nature. One study of CABI&#xD;
      following source control procedures evaluated a short course of antibiotics (4 days) compared&#xD;
      to a course of up to 2 weeks after clinical and biochemical improvement (up to 10 days).&#xD;
      Whilst there was little difference in outcomes, both groups had a high relapse rate of&#xD;
      approximately 15%. In addition, it is common for source control procedures not to be&#xD;
      completed in routine clinical practice, being completed in only 17% of Leeds patients with&#xD;
      post-operative CABI (Rothwell 2016). In this Leeds data of post-operative CABIs, where source&#xD;
      control rates are low relapse rates were 40% (Rothwell 2016). For CABI infections, standard&#xD;
      UK management is variable and involves between 4 and 42 days' antibiotics. This indicates an&#xD;
      unacceptably high relapse rate in patients treated for CABI where source control is and is&#xD;
      not undertaken. We therefore propose to investigate if long course antibiotic therapy (28&#xD;
      days) is clinically more effective than short course antibiotics (4 days) in preventing&#xD;
      relapses of CABI. This study will include patients who have and have not undergone source&#xD;
      control procedures which will be completed as per standard practice.&#xD;
&#xD;
      Complicated intra-abdominal infections require source control when possible, e.g. a surgical&#xD;
      procedure to remove an infection, and antibiotic therapy to obtain cure. Source control is&#xD;
      not always possible. CABIs are associated with mortality and prolongation of hospitalisation.&#xD;
      After apparently effective treatment, potentially including source control procedures and&#xD;
      antibiotics, infections can relapse. There are a number of reasons for relapse; one is that&#xD;
      antibiotic treatment may not have been given for long enough to eradicate the bacteria from,&#xD;
      what should be, a sterile intra-abdominal cavity. Antibiotics are given until a patient is&#xD;
      better, but not until all bacteria are eradicated, allowing them to regrow and re-start an&#xD;
      infection. Standard antibiotic duration is variable: some doctors provide long courses and&#xD;
      others short. We therefore want to compare durations, to see if longer courses of antibiotics&#xD;
      are able to help prevent these relapses, or if shorter courses are as effective but have&#xD;
      fewer side effects. We have not identified closely related strategies which may optimise the&#xD;
      management of CABIs.&#xD;
&#xD;
      The research hypothesis is therefore: In patients with CABI, regardless of source control&#xD;
      intervention, there will be a lower relapse rate when treated with 28 days of antibiotics&#xD;
      compared to ≤10 days of antibiotics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">September 1, 2018</completion_date>
  <primary_completion_date type="Actual">September 1, 2018</primary_completion_date>
  <phase>Phase 2</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants willing to be randomised, the willingness of clinicians to allow participants to be recruited &amp; follow up rates.</measure>
    <time_frame>90 days</time_frame>
    <description>Screening logs, recruitment rates and follow up rates will be recorded to determine the feasibility of performing a larger study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who have their antibiotic therapy changed as a consequence of allocation to a certain treatment arm.</measure>
    <time_frame>Either ≤ 10 days or 28 days depending on allocation.</time_frame>
    <description>Antibiotic therapy received including any changes to treatment will be recorded.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The number of participants who relapse after treatment of complicated intra-abdominal infection.</measure>
    <time_frame>90 days</time_frame>
    <description>Frequency of complicated intra-abdominal infection (CABI) relapse with 90 days. A relapse can only occur after surgical and antibiotic therapy to manage the primary CABI has been considered successful. This will normally be demonstrated by antibiotics being stopped and no further source control procedures planned. The diagnosis of a definite CABI relapse defined as 'a combination of radiological AND clinical features consistent with CABI including a fluid collection, a temperature of ≥38 degrees and a neutrophilia (neutrophil count &gt; 7.5 x 10*9/L) or Intra-operative confirmation of an abscess'. The diagnosis of a probable CABI relapse will be defined as ' in the absence of radiological imaging, but where no other source of infection was identified, and the patient was managed for a relapsed CABI'</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of all infections after treatment of complicated intra-abdominal infection</measure>
    <time_frame>90 days</time_frame>
    <description>The diagnosis of hospital acquired infections will be based on either a clinical diagnosis based on physician assessment or on definitions outlined by the 'Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute-care hospitals' https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/542039/ECDC_PHE_HAI_AU_PPS_2016_single_codebook.pdf</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total antibiotic consumption</measure>
    <time_frame>90 days</time_frame>
    <description>Days of antibiotic therapy within 90 days of antibiotic therapy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay within 90 days of diagnosis</measure>
    <time_frame>90 days</time_frame>
    <description>The length of hospital stay after diagnosis of complicated intra-abdominal infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality rate after treatment of complicated intra-abdominal infection.</measure>
    <time_frame>90 days</time_frame>
    <description>Assessed by the 90 day mortality after diagnosis of a complicated intra-abdominal infection.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of participants with complications from antibiotic therapy including Clostridium difficile infection (CDI) diarrhoea and catheter related blood stream infection (CRBSI)</measure>
    <time_frame>90 days</time_frame>
    <description>Measured by the rate of adverse events, CDI and CRBSI within 90 days of diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of source control procedures required for the management of CABI</measure>
    <time_frame>90 days</time_frame>
    <description>Measured by the number source control procedures required for the management of CABI within 90 days of CABI diagnosis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life after treatment of complicated intra-abdominal infection</measure>
    <time_frame>Baseline, at 30 days, at 90 days and (if occurs) at time of relapse</time_frame>
    <description>Assessed by a quality of life questionnaire (EQ-5D)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Feasibility of using scoring systems in complicated intra-abdominal infections</measure>
    <time_frame>90 days</time_frame>
    <description>Measured by the ability to gather the data required to complete severity scores</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Complicated Intraabdominal Infections</condition>
  <arm_group>
    <arm_group_label>Long course antibiotic therapy (28 days)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Antibiotic therapy for a duration of 28 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Short course antibiotic therapy (≤10 days)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Antibiotic therapy for a duration of ≤10 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>&lt; 10 days of antibiotics</intervention_name>
    <description>Antibiotic duration</description>
    <arm_group_label>Short course antibiotic therapy (≤10 days)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>28 days of antibiotics</intervention_name>
    <description>Antibiotic duration</description>
    <arm_group_label>Long course antibiotic therapy (28 days)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults &gt;18 years&#xD;
&#xD;
          -  The diagnosis of a definite CABI&#xD;
&#xD;
          -  Capable of giving informed consent&#xD;
&#xD;
          -  No practical or clinical barriers to consuming 28 days of antibiotic therapy, which&#xD;
             may include consumption of antibiotics at home&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  a CABI diagnosed within the previous year&#xD;
&#xD;
          -  a CABI diagnosed &gt;6 days prior to screening&#xD;
&#xD;
          -  uncomplicated cholecystitis/cholangitis/gall bladder empyema (no perforation or&#xD;
             extra-biliary abscess&#xD;
&#xD;
          -  a skin and soft tissue infection/abscess not communicating with the peritoneal space&#xD;
&#xD;
          -  primary complicated or uncomplicated appendicitis managed surgically&#xD;
&#xD;
          -  intra-abdominal infection associated with pancreatitis, pelvic inflammatory disease,&#xD;
             primary (spontaneous) bacterial peritonitis (SBP), continuous ambulatory peritoneal&#xD;
             dialysis peritonitis (CAPD peritonitis) and Clostridium difficile infection.&#xD;
             concurrent infection requiring more than 10 days of therapy&#xD;
&#xD;
          -  Infection with a highly resistant bacterium such that antibiotic treatment is&#xD;
             considered to be a significantly sub-optimal by the treating microbiologist e.g.&#xD;
             multi-resistant carbapenemase producing Entrobacteriacea&#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>Andrew Kirby, MBChB</last_name>
    <role>Principal Investigator</role>
    <affiliation>Leeds Teaching Hospitals NHS Trust</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Leeds Teaching Hospitals NHS Trust</name>
      <address>
        <city>Leeds</city>
        <state>Yorkshire</state>
        <zip>LS1 3EX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010 Jan 15;50(2):133-64. doi: 10.1086/649554. Erratum In: Clin Infect Dis. 2010 Jun 15;50(12):1695. Dosage error in article text.</citation>
    <PMID>20034345</PMID>
  </reference>
  <reference>
    <citation>Rothwell A, Burke D, Burnside G, Kirby A. Characteristics of Organ Space Surgical Site Infection after colorectal surgery. In preparation.</citation>
  </reference>
  <reference>
    <citation>DeFrances CJ, Cullen KA, Kozak LJ. National Hospital Discharge Survey: 2005 annual summary with detailed diagnosis and procedure data. Vital Health Stat 13. 2007 Dec;(165):1-209.</citation>
    <PMID>18350768</PMID>
  </reference>
  <reference>
    <citation>Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Regnier B. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995 Sep 27;274(12):968-74.</citation>
    <PMID>7674528</PMID>
  </reference>
  <reference>
    <citation>von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct 20;370(9596):1453-7. doi: 10.1016/S0140-6736(07)61602-X.</citation>
    <PMID>18064739</PMID>
  </reference>
  <reference>
    <citation>Sterne JA, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, Wood AM, Carpenter JR. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009 Jun 29;338:b2393. doi: 10.1136/bmj.b2393.</citation>
    <PMID>19564179</PMID>
  </reference>
  <reference>
    <citation>Sawyer RG, Claridge JA, Nathens AB, Rotstein OD, Duane TM, Evans HL, Cook CH, O'Neill PJ, Mazuski JE, Askari R, Wilson MA, Napolitano LM, Namias N, Miller PR, Dellinger EP, Watson CM, Coimbra R, Dent DL, Lowry SF, Cocanour CS, West MA, Banton KL, Cheadle WG, Lipsett PA, Guidry CA, Popovsky K; STOP-IT Trial Investigators. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015 May 21;372(21):1996-2005. doi: 10.1056/NEJMoa1411162. Erratum In: N Engl J Med. 2018 Jan 25;:null.</citation>
    <PMID>25992746</PMID>
  </reference>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>August 23, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>June 2, 2021</last_update_submitted>
  <last_update_submitted_qc>June 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 3, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Leeds</investigator_affiliation>
    <investigator_full_name>Andrew Kirby</investigator_full_name>
    <investigator_title>Associate clinical 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>Intraabdominal Infections</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>Antibiotics, Antitubercular</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 18, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03265834/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/34/NCT03265834/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03265834
org study id: MB16/156
nct id: NCT03265834
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Complicated intra-ABdominal Infections (CABIs) are abdominal infections where there is an
      abscess inside the abdomen, or a hole (perforation) in an abdominal organ such that infected
      material e.g. faeces, leaks into the abdominal cavity. A recent review of CABIs after gut
      surgery found that they can occur in several ways. They can occur in different parts of the
      abdomen, can be different sizes, and may or may not be caused by a perforated bowel.
      Management includes, where possible, surgical drainage of an abscess or treatment of the
      damaged bowel. In addition, all patients are given antibiotic therapy. Despite the varied
      ways that CABIs occur, we currently tend to treat all CABIs with antibiotics in a similar
      way. CABIs are associated with significant morbidity and mortality. Despite a significant
      amount of disease there is little clinical evidence with which to base treatment on. One
      research study evaluated a short course of antibiotics (4 days) compared with a longer course
      (up to 10 days) in combination with surgical removal of infection. There was little
      difference in outcomes, but in both groups about 1 out of every 7 patients had a relapse. A
      recent review of patients with CABI in Leeds, not in a research study and where surgical
      removal infection is uncommon and antibiotic durations were short, showed that the risk of
      relapse was even higher (about 1 in every 3 patients). The antibiotic management of CABIs in
      the UK is variable and involves giving between 4 days to 28 days of antibiotics.

      In summary, there is an unacceptably high relapse rate in patients treated for CABI, and
      uncertainty about the best length of antibiotic therapy that should be used to prevent these
      relapses. We therefore propose to investigate if long course antibiotic therapy (28 days) is
      more effective than short course antibiotics (≤10 days) in preventing relapses of CABI.
Complicated intra-abdominal infection (CABI) extends beyond the hollow viscus of origin into
      the peritoneal space and is associated with either abscess formation or peritonitis [Solomkin
      2010]. CABIs are heterogeneous in aetiology and include spontaneous infections arising from a
      perforated viscus, including the stomach, biliary tree, colon, appendix and reproductive
      organs. In addition there are post-operative complications such as peritonitis, abscess, and
      failure of surgical anastomoses. CABIs are also heterogeneous in their characteristics. A
      recent review of organ space Surgical Site Infections (SSI-Os) after colorectal surgery
      demonstrated that infections were varied with regard their location, as well as size and
      number and nature of collections, and presence of an ongoing source e.g. anastomotic
      breakdown (Rothwell 2016). Despite the varied origin of these infections, there are similar
      management strategies which centre on the source control, e.g. drainage of intra-abdominal
      fluid collections, and administration of antibiotic therapy. CABIs are a common in-hospital
      clinical challenge, in part due to the varied pathology they are caused by, and are
      associated with significant morbidity and mortality (DeFrances 2005, Brun-Buisson 1995).
      Despite this burden of disease, there is little clinical evidence with which to base
      treatment on, even before taking account of their heterogeneous nature. One study of CABI
      following source control procedures evaluated a short course of antibiotics (4 days) compared
      to a course of up to 2 weeks after clinical and biochemical improvement (up to 10 days).
      Whilst there was little difference in outcomes, both groups had a high relapse rate of
      approximately 15%. In addition, it is common for source control procedures not to be
      completed in routine clinical practice, being completed in only 17% of Leeds patients with
      post-operative CABI (Rothwell 2016). In this Leeds data of post-operative CABIs, where source
      control rates are low relapse rates were 40% (Rothwell 2016). For CABI infections, standard
      UK management is variable and involves between 4 and 42 days' antibiotics. This indicates an
      unacceptably high relapse rate in patients treated for CABI where source control is and is
      not undertaken. We therefore propose to investigate if long course antibiotic therapy (28
      days) is clinically more effective than short course antibiotics (4 days) in preventing
      relapses of CABI. This study will include patients who have and have not undergone source
      control procedures which will be completed as per standard practice.

      Complicated intra-abdominal infections require source control when possible, e.g. a surgical
      procedure to remove an infection, and antibiotic therapy to obtain cure. Source control is
      not always possible. CABIs are associated with mortality and prolongation of hospitalisation.
      After apparently effective treatment, potentially including source control procedures and
      antibiotics, infections can relapse. There are a number of reasons for relapse; one is that
      antibiotic treatment may not have been given for long enough to eradicate the bacteria from,
      what should be, a sterile intra-abdominal cavity. Antibiotics are given until a patient is
      better, but not until all bacteria are eradicated, allowing them to regrow and re-start an
      infection. Standard antibiotic duration is variable: some doctors provide long courses and
      others short. We therefore want to compare durations, to see if longer courses of antibiotics
      are able to help prevent these relapses, or if shorter courses are as effective but have
      fewer side effects. We have not identified closely related strategies which may optimise the
      management of CABIs.

      The research hypothesis is therefore: In patients with CABI, regardless of source control
      intervention, there will be a lower relapse rate when treated with 28 days of antibiotics
      compared to ≤10 days of antibiotics.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants willing to be randomised, the willingness of clinicians to allow participants to be recruited & follow up rates.
time frame: 90 days
description: Screening logs, recruitment rates and follow up rates will be recorded to determine the feasibility of performing a larger study.
measure: Number of participants who have their antibiotic therapy changed as a consequence of allocation to a certain treatment arm.
time frame: Either ≤ 10 days or 28 days depending on allocation.
description: Antibiotic therapy received including any changes to treatment will be recorded.
measure: The number of participants who relapse after treatment of complicated intra-abdominal infection.
time frame: 90 days
description: Frequency of complicated intra-abdominal infection (CABI) relapse with 90 days. A relapse can only occur after surgical and antibiotic therapy to manage the primary CABI has been considered successful. This will normally be demonstrated by antibiotics being stopped and no further source control procedures planned. The diagnosis of a definite CABI relapse defined as 'a combination of radiological AND clinical features consistent with CABI including a fluid collection, a temperature of ≥38 degrees and a neutrophilia (neutrophil count > 7.5 x 10*9/L) or Intra-operative confirmation of an abscess'. The diagnosis of a probable CABI relapse will be defined as ' in the absence of radiological imaging, but where no other source of infection was identified, and the patient was managed for a relapsed CABI'
measure: Number of all infections after treatment of complicated intra-abdominal infection
time frame: 90 days
description: The diagnosis of hospital acquired infections will be based on either a clinical diagnosis based on physician assessment or on definitions outlined by the 'Point prevalence survey of healthcare-associated infections and antimicrobial use in European acute-care hospitals' https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/542039/ECDC_PHE_HAI_AU_PPS_2016_single_codebook.pdf
measure: Total antibiotic consumption
time frame: 90 days
description: Days of antibiotic therapy within 90 days of antibiotic therapy
measure: Length of hospital stay within 90 days of diagnosis
time frame: 90 days
description: The length of hospital stay after diagnosis of complicated intra-abdominal infection
measure: Mortality rate after treatment of complicated intra-abdominal infection.
time frame: 90 days
description: Assessed by the 90 day mortality after diagnosis of a complicated intra-abdominal infection.
measure: The number of participants with complications from antibiotic therapy including Clostridium difficile infection (CDI) diarrhoea and catheter related blood stream infection (CRBSI)
time frame: 90 days
description: Measured by the rate of adverse events, CDI and CRBSI within 90 days of diagnosis.
measure: The number of source control procedures required for the management of CABI
time frame: 90 days
description: Measured by the number source control procedures required for the management of CABI within 90 days of CABI diagnosis.
measure: Quality of life after treatment of complicated intra-abdominal infection
time frame: Baseline, at 30 days, at 90 days and (if occurs) at time of relapse
description: Assessed by a quality of life questionnaire (EQ-5D)
measure: Feasibility of using scoring systems in complicated intra-abdominal infections
time frame: 90 days
description: Measured by the ability to gather the data required to complete severity scores
arm group label: Long course antibiotic therapy (28 days)
arm group type: Experimental
description: Antibiotic therapy for a duration of 28 days
arm group label: Short course antibiotic therapy (≤10 days)
arm group type: Active Comparator
description: Antibiotic therapy for a duration of ≤10 days
intervention type: Other
intervention name: < 10 days of antibiotics
description: Antibiotic duration
arm group label: Short course antibiotic therapy (≤10 days)
intervention type: Other
intervention name: 28 days of antibiotics
description: Antibiotic duration
arm group label: Long course antibiotic therapy (28 days)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Kirby, MBChB
role: Principal Investigator
affiliation: Leeds Teaching Hospitals NHS Trust
facility: 
country: United Kingdom
citation: Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, O'Neill PJ, Chow AW, Dellinger EP, Eachempati SR, Gorbach S, Hilfiker M, May AK, Nathens AB, Sawyer RG, Bartlett JG. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010 Jan 15;50(2):133-64. doi: 10.1086/649554. Erratum In: Clin Infect Dis. 2010 Jun 15;50(12):1695. Dosage error in article text.
PMID: 20034345
citation: Rothwell A, Burke D, Burnside G, Kirby A. Characteristics of Organ Space Surgical Site Infection after colorectal surgery. In preparation.
citation: DeFrances CJ, Cullen KA, Kozak LJ. National Hospital Discharge Survey: 2005 annual summary with detailed diagnosis and procedure data. Vital Health Stat 13. 2007 Dec;(165):1-209.
PMID: 18350768
citation: Brun-Buisson C, Doyon F, Carlet J, Dellamonica P, Gouin F, Lepoutre A, Mercier JC, Offenstadt G, Regnier B. Incidence, risk factors, and outcome of severe sepsis and septic shock in adults. A multicenter prospective study in intensive care units. French ICU Group for Severe Sepsis. JAMA. 1995 Sep 27;274(12):968-74.
PMID: 7674528
citation: von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007 Oct 20;370(9596):1453-7. doi: 10.1016/S0140-6736(07)61602-X.
PMID: 18064739
citation: Sterne JA, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, Wood AM, Carpenter JR. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009 Jun 29;338:b2393. doi: 10.1136/bmj.b2393.
PMID: 19564179
citation: Sawyer RG, Claridge JA, Nathens AB, Rotstein OD, Duane TM, Evans HL, Cook CH, O'Neill PJ, Mazuski JE, Askari R, Wilson MA, Napolitano LM, Namias N, Miller PR, Dellinger EP, Watson CM, Coimbra R, Dent DL, Lowry SF, Cocanour CS, West MA, Banton KL, Cheadle WG, Lipsett PA, Guidry CA, Popovsky K; STOP-IT Trial Investigators. Trial of short-course antimicrobial therapy for intraabdominal infection. N Engl J Med. 2015 May 21;372(21):1996-2005. doi: 10.1056/NEJMoa1411162. Erratum In: N Engl J Med. 2018 Jan 25;:null.
PMID: 25992746
responsible party type: Principal Investigator
investigator affiliation: University of Leeds
investigator full name: Andrew Kirby
investigator title: Associate clinical professor
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Intraabdominal Infections
mesh term: Anti-Bacterial Agents
mesh term: Antibiotics, Antitubercular
sharing ipd: No
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