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/NCT05981430</url>
    </required_header>
    <id_info>
      <org_study_id>UW 19-512</org_study_id>
      <nct_id>NCT05981430</nct_id>
    </id_info>
    <brief_title>Fecal Microbiota Transplantation for Decolonization of Carbapenem-resistant Enterobacteriaceae</brief_title>
    <acronym>FMT</acronym>
    <official_title>Fecal Microbiota Transplantation for Decolonization of Carbapenem-resistant Enterobacteriaceae: a Double Blind Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>The University of Hong Kong</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>The University of Hong Kong</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The emergence of multidrug-resistant organisms (MDROs) has become one of the major threats to&#xD;
        the healthcare system in Hong Kong in recent years. The situation is particularly worrisome&#xD;
        for carbapenem-resistant Enterobacteriaceae (CRE). Taking Queen Mary Hospital as an example,&#xD;
        the number of CRE cases has surged from 24 in year 2014 to 625 in year 2021. The case burden&#xD;
        in Hong Kong is therefore substantial when all 43 public hospitals and institutions in Hong&#xD;
        Kong are considered. With the widespread use of broad-spectrum antibiotics and active case&#xD;
        screening, the number of CRE cases is expected to further increase in an exponential manner.&#xD;
  &#xD;
        Given that colonization with MDROs is due to gut dysbiosis from antibiotic use, a normal&#xD;
        intestinal microbiota is apparently crucial in protecting hosts from colonization with MDROs&#xD;
        including CRE. Fecal microbiota transplantation (FMT), which involves the infusion of stool&#xD;
        from a healthy donor to the gastrointestinal (GI) tract of a recipient, has gained popularity&#xD;
        in recent years to restore colonic microbial diversity in various diseases associated with&#xD;
        gut dysbiosis, e.g. Clostridium difficile (CD) infection, ulcerative colitis and even&#xD;
        metabolic diseases. The investigators aim to conduct a double-blind randomized controlled&#xD;
        trial to evaluate the benefit of FMT via lower GI delivery (enema) on CRE clearance.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        CRE colonization is associated with a 16.5% risk of infection with a 10% mortality rate. CRE&#xD;
        also poses a tremendous strain on the healthcare cost as well as the medical/nursing&#xD;
        manpower. The hospital stay is lengthened by two-fold for CRE-infected cases compared with&#xD;
        non-infected cases. CRE carriers frequently have to stay in acute hospitals for extended&#xD;
        periods of time after settling their acute illnesses, both because of the logistic&#xD;
        infeasibility of them being transferred to rehabilitation units or nursing homes, which are&#xD;
        devoid of isolation rooms.&#xD;
  &#xD;
        Proactive measures have been implemented in hospitals worldwide to prevent the spread of&#xD;
        MDROs, especially to vulnerable individuals. Such measures usually include surveillance&#xD;
        culture, contact tracing, isolation of carriers and environmental disinfection. Nevertheless,&#xD;
        isolation facilities are not always readily available, particularly in resource-limited&#xD;
        regions. In addition, contact isolation may result in various adverse effects on the mental&#xD;
        well-being of isolated patients, such as depression, anxiety and anger. Time spent with&#xD;
        patients in isolation by healthcare workers is less, with a negative effect on patient safety&#xD;
        with an eight-fold increase in the risk of adverse events due to supportive care failure.&#xD;
  &#xD;
        There has been a growing interest in extending FMT for the decolonization of CRE. However,&#xD;
        most of the studies are limited to case reports or case series with small sample sizes&#xD;
        (ranging from 10 to 39 patients) as shown by a recent systematic review. The pooled rate of&#xD;
        CRE decolonization is promising at 62.1%. However, a randomized controlled trial (RCT)&#xD;
        remains the most optimal study design to investigate the true beneficial effect of FMT on CRE&#xD;
        decolonization. FMT via enema route has several advantages over upper GI delivery or&#xD;
        colonoscopy. First, the administration of fecal suspension via a feeding tube may not be&#xD;
        acceptable to some patients. Second, colonoscopy carries complications of gut perforation,&#xD;
        aspiration, and cardiopulmonary suppression from the use of sedatives, in particular among&#xD;
        frail and elder patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 20, 2023</start_date>
    <completion_date type="Anticipated">August 19, 2025</completion_date>
    <primary_completion_date type="Anticipated">August 19, 2025</primary_completion_date>
    <phase>N/A</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>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>CRE clearance rate</measure>
      <time_frame>1 month post-FMT</time_frame>
      <description>CRE clearance rate via enema</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>CRE clearance rate</measure>
      <time_frame>1 week, 2 week, 3 month, 6 month and 12 month post-FMT</time_frame>
      <description>CRE clearance rate post-FMT</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause mortality</measure>
      <time_frame>1 month, 3 month, 6 month and 12 month post-FMT</time_frame>
      <description>All-cause mortality post-FMT</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">80</enrollment>
    <condition>Carbapenem-Resistant Enterobacteriaceae Infection</condition>
    <condition>Fecal Microbiota Transplantation</condition>
    <arm_group>
      <arm_group_label>Fecal microbiota transplant</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>This group's subject will receive an infusion of 125mL fecal suspension via enema.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham fecal microbiota transplant</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>This group's subject will receive 125mL placebo enema comprised of normal saline with 15% glycerol and brown food colouring 204 (Americolorcorp) as a sham procedure.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Fecal microbiota transplant</intervention_name>
      <description>Active comparator will receive infusion of 125mL fecal suspension via enema</description>
      <arm_group_label>Fecal microbiota transplant</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Sham fecal microbiota transplant</intervention_name>
      <description>Placebo comparator will receive 125mL placebo enema comprised of normal saline with 15% glycerol and brown food coloring 204 (Americolorcorp).</description>
      <arm_group_label>Sham fecal microbiota transplant</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  All adult patients aged 18 or above admitted to the medical ward of Queen Mary&#xD;
               Hospital, the teaching hospital of the University of Hong Kong&#xD;
  &#xD;
            -  Rectal swabs or stool specimens showing the presence of CRE&#xD;
  &#xD;
            -  Positive CRE specimen within one week of commencement&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  Severe immunodeficiency (e.g. advanced human immunodeficiency virus infection (CD4&#xD;
               lymphocyte count ≤200/mm3), myelosuppressive chemotherapy)&#xD;
  &#xD;
            -  Significant neutropenia (absolute neutrophil count ≤1.0 x 109/L)&#xD;
  &#xD;
            -  Recent antibiotic use within 30 days prior to consent&#xD;
  &#xD;
            -  Contraindications for retention enema (intestinal obstruction, ileus and gut&#xD;
               perforation).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ka Shing Cheung</last_name>
      <role>Principal Investigator</role>
      <affiliation>The University of Hong Kong</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ka Shing Cheung</last_name>
      <phone>22554769</phone>
      <email>cks634@hku.hk</email>
    </overall_contact>
    <reference>
      <citation>Backman C, Taylor G, Sales A, Marck PB. An integrative review of infection prevention and control programs for multidrug-resistant organisms in acute care hospitals: a socio-ecological perspective. Am J Infect Control. 2011 Jun;39(5):368-378. doi: 10.1016/j.ajic.2010.07.017. Epub 2011 Mar 23.</citation>
      <PMID>21429622</PMID>
    </reference>
    <reference>
      <citation>Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma N, Iqbal TH. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017 Sep;46(5):479-493. doi: 10.1111/apt.14201. Epub 2017 Jul 14.</citation>
      <PMID>28707337</PMID>
    </reference>
    <reference>
      <citation>Macareno-Castro J, Solano-Salazar A, Dong LT, Mohiuddin M, Espinoza JL. Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review. J Infect. 2022 Jun;84(6):749-759. doi: 10.1016/j.jinf.2022.04.028. Epub 2022 Apr 21.</citation>
      <PMID>35461908</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>July 31, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 9, 2023</last_update_submitted>
    <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
      <investigator_full_name>Cheung Ka Shing</investigator_full_name>
      <investigator_title>Clinical assistant professor. https://medic.hku.hk/en/Staff/University-Academic-Staff/Dr-CHEUNG-Ka-Shing-Michael/Dr-CHEUNG-Ka-Shing-Michael-Profile</investigator_title>
    </responsible_party>
    <keyword>FMT</keyword>
    <keyword>CRE</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Enterobacteriaceae Infections</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT05981430
  org study id: UW 19-512
  nct id: NCT05981430
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  The emergence of multidrug-resistant organisms (MDROs) has become one of the major threats to
        the healthcare system in Hong Kong in recent years. The situation is particularly worrisome
        for carbapenem-resistant Enterobacteriaceae (CRE). Taking Queen Mary Hospital as an example,
        the number of CRE cases has surged from 24 in year 2014 to 625 in year 2021. The case burden
        in Hong Kong is therefore substantial when all 43 public hospitals and institutions in Hong
        Kong are considered. With the widespread use of broad-spectrum antibiotics and active case
        screening, the number of CRE cases is expected to further increase in an exponential manner.
  
        Given that colonization with MDROs is due to gut dysbiosis from antibiotic use, a normal
        intestinal microbiota is apparently crucial in protecting hosts from colonization with MDROs
        including CRE. Fecal microbiota transplantation (FMT), which involves the infusion of stool
        from a healthy donor to the gastrointestinal (GI) tract of a recipient, has gained popularity
        in recent years to restore colonic microbial diversity in various diseases associated with
        gut dysbiosis, e.g. Clostridium difficile (CD) infection, ulcerative colitis and even
        metabolic diseases. The investigators aim to conduct a double-blind randomized controlled
        trial to evaluate the benefit of FMT via lower GI delivery (enema) on CRE clearance.
  CRE colonization is associated with a 16.5% risk of infection with a 10% mortality rate. CRE
        also poses a tremendous strain on the healthcare cost as well as the medical/nursing
        manpower. The hospital stay is lengthened by two-fold for CRE-infected cases compared with
        non-infected cases. CRE carriers frequently have to stay in acute hospitals for extended
        periods of time after settling their acute illnesses, both because of the logistic
        infeasibility of them being transferred to rehabilitation units or nursing homes, which are
        devoid of isolation rooms.
  
        Proactive measures have been implemented in hospitals worldwide to prevent the spread of
        MDROs, especially to vulnerable individuals. Such measures usually include surveillance
        culture, contact tracing, isolation of carriers and environmental disinfection. Nevertheless,
        isolation facilities are not always readily available, particularly in resource-limited
        regions. In addition, contact isolation may result in various adverse effects on the mental
        well-being of isolated patients, such as depression, anxiety and anger. Time spent with
        patients in isolation by healthcare workers is less, with a negative effect on patient safety
        with an eight-fold increase in the risk of adverse events due to supportive care failure.
  
        There has been a growing interest in extending FMT for the decolonization of CRE. However,
        most of the studies are limited to case reports or case series with small sample sizes
        (ranging from 10 to 39 patients) as shown by a recent systematic review. The pooled rate of
        CRE decolonization is promising at 62.1%. However, a randomized controlled trial (RCT)
        remains the most optimal study design to investigate the true beneficial effect of FMT on CRE
        decolonization. FMT via enema route has several advantages over upper GI delivery or
        colonoscopy. First, the administration of fecal suspension via a feeding tube may not be
        acceptable to some patients. Second, colonoscopy carries complications of gut perforation,
        aspiration, and cardiopulmonary suppression from the use of sedatives, in particular among
        frail and elder patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Care Provider, Investigator)
  measure: CRE clearance rate
  time frame: 1 month post-FMT
  description: CRE clearance rate via enema
  measure: CRE clearance rate
  time frame: 1 week, 2 week, 3 month, 6 month and 12 month post-FMT
  description: CRE clearance rate post-FMT
  measure: All-cause mortality
  time frame: 1 month, 3 month, 6 month and 12 month post-FMT
  description: All-cause mortality post-FMT
  arm group label: Fecal microbiota transplant
  arm group type: Active Comparator
  description: This group's subject will receive an infusion of 125mL fecal suspension via enema.
  arm group label: Sham fecal microbiota transplant
  arm group type: Placebo Comparator
  description: This group's subject will receive 125mL placebo enema comprised of normal saline with 15% glycerol and brown food colouring 204 (Americolorcorp) as a sham procedure.
  intervention type: Biological
  intervention name: Fecal microbiota transplant
  description: Active comparator will receive infusion of 125mL fecal suspension via enema
  arm group label: Fecal microbiota transplant
  intervention type: Biological
  intervention name: Sham fecal microbiota transplant
  description: Placebo comparator will receive 125mL placebo enema comprised of normal saline with 15% glycerol and brown food coloring 204 (Americolorcorp).
  arm group label: Sham fecal microbiota transplant
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: Ka Shing Cheung
  role: Principal Investigator
  affiliation: The University of Hong Kong
  last name: Ka Shing Cheung
  phone: 22554769
  email: cks634@hku.hk
  citation: Backman C, Taylor G, Sales A, Marck PB. An integrative review of infection prevention and control programs for multidrug-resistant organisms in acute care hospitals: a socio-ecological perspective. Am J Infect Control. 2011 Jun;39(5):368-378. doi: 10.1016/j.ajic.2010.07.017. Epub 2011 Mar 23.
  PMID: 21429622
  citation: Quraishi MN, Widlak M, Bhala N, Moore D, Price M, Sharma N, Iqbal TH. Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection. Aliment Pharmacol Ther. 2017 Sep;46(5):479-493. doi: 10.1111/apt.14201. Epub 2017 Jul 14.
  PMID: 28707337
  citation: Macareno-Castro J, Solano-Salazar A, Dong LT, Mohiuddin M, Espinoza JL. Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review. J Infect. 2022 Jun;84(6):749-759. doi: 10.1016/j.jinf.2022.04.028. Epub 2022 Apr 21.
  PMID: 35461908
  responsible party type: Principal Investigator
  investigator affiliation: The University of Hong Kong
  investigator full name: Cheung Ka Shing
  investigator title: Clinical assistant professor. https://medic.hku.hk/en/Staff/University-Academic-Staff/Dr-CHEUNG-Ka-Shing-Michael/Dr-CHEUNG-Ka-Shing-Michael-Profile
  mesh term: Enterobacteriaceae Infections
  sharing ipd: No