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/NCT06001333</url>
    </required_header>
    <id_info>
      <org_study_id>2023-06-007</org_study_id>
      <nct_id>NCT06001333</nct_id>
    </id_info>
    <brief_title>Efficacy and Safety of FMT for the Decolonization of MDROs in the Intestinal Tract</brief_title>
    <official_title>Efficacy and Safety of Fecal Microbiota Transplantation for the Decolonization of Multidrug-Resistant Organisms in the Intestinal Tract: An Unblinded Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chuncheon Sacred Heart Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Severance Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>National Institute of Health, Korea</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Chuncheon Sacred Heart Hospital</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>
        The goal of this unblinded randomized controlled trial is to evaluate the efficacy and safety&#xD;
        of fecal microbiota transplantation for the decolonization of carbapenemase-producing&#xD;
        carbapenem-resistant Enterobacteriaceae (CP-CRE) or vancomycin-resistant Enterococci (VRE) in&#xD;
        the intestinal tract. The study is planned to be conducted to test the superiority hypothesis&#xD;
        that the decolonization success rate in the FMT group is higher compared to the non-FMT&#xD;
        group. Outcome analysis will be conducted through intention-to-treat analysis, modified&#xD;
        intention-to-treat analysis, and per-protocol analysis.&#xD;
  &#xD;
        The main questions it aims to answer are:&#xD;
  &#xD;
          -  primary endpoint: Rate of Decolonization of Multidrug-Resistant Organisms (CP-CRE or&#xD;
             VRE) at 1 Month After Fecal Microbiota Transplantation (FMT).&#xD;
  &#xD;
          -  secondary endpoint: Rates of Multidrug-Resistant Organism decolonization at 3 months, 6&#xD;
             months, and 1 year after FMT / Post-FMT Multidrug-Resistant Organism Recolonization Rate&#xD;
             and Infection Rate.&#xD;
  &#xD;
        Patients colonized with multidrug-resistant organisms in the gastrointestinal tract are&#xD;
        divided into two groups through obtaining written consent from the patients and random&#xD;
        allocation: the Fecal Microbiota Transplantation group (FMT group), which receives FMT, and&#xD;
        the control group (non-FMT group), which is observed without FMT. The decolonization status&#xD;
        of multidrug-resistant organisms will be monitored every 3-7 days after FMT until three&#xD;
        consecutive negative results.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The study is planned to be conducted at Chuncheon Sacred Heart Hospital and Severance&#xD;
        Hospital, using randomization with equal allocation to allocate patients into FMT (Fecal&#xD;
        Microbiota Transplantation) and non-FMT groups. The study parameters are set with an alpha&#xD;
        error of 0.05 and beta error of 0.2. Considering the findings from previous research, a delta&#xD;
        value (effect size) was determined for sample size calculation. Based on this calculated&#xD;
        sample size, for CP-CRE, 80 patients will be recruited in the FMT group compared to 68&#xD;
        patients in the non-FMT group. For VRE, 48 patients will be recruited in the FMT group&#xD;
        compared to 44 patients in the non-FMT group.&#xD;
  &#xD;
        Patients who have provided written consent for participation in the study will be required to&#xD;
        maintain fasting starting from the evening before the procedure, after discontinuing&#xD;
        broad-spectrum antibiotics for a minimum of 3-7 days. Subsequently, a bowel preparation will&#xD;
        be carried out twice - the evening before and the morning of the procedure. Once the bowel&#xD;
        preparation is complete, 1 hour before the procedure, patients will receive loperamide to&#xD;
        reduce bowel movements and then proceed to the endoscopy suite.&#xD;
  &#xD;
        Fecal microbiota transplantation (FMT) will be carried out with the acquired frozen donor&#xD;
        stool, which will be thawed for 2 hours at room temperature following purchase and delivery&#xD;
        from a stool bank, under the consent and supervision of the patient or guardian. Frozen stool&#xD;
        from carefully screened donors who have passed the rigorous screening of both Stage 1&#xD;
        clinical assessment and Stage 2 laboratory tests (including evaluation for antibiotic&#xD;
        resistance organisms) will be supplied from a stool bank of Microbiotix inc.&#xD;
  &#xD;
        The FMT procedure will be conducted in collaboration with the research team in the Division&#xD;
        of Gastroenterology. During the procedure, no tissue biopsy or excessive endoscope insertion&#xD;
        will be performed. The FMT involves the simple infusion of thawed donor stool into the&#xD;
        terminal ileum under colonoscopy, which takes approximately 5-10 minutes. The procedure&#xD;
        carries minimal risk of bleeding, perforation, or aspiration. In most cases, it will be&#xD;
        performed under sedation with a colonoscopy. If smooth insertion of the colonoscope or proper&#xD;
        visualization of the colon is hindered, or if colonic preparation is not successful,&#xD;
        Esophagogastroduodenoscopy (EGD) will be performed with sedation, and thawed donor stool will&#xD;
        be infused into the third portion of the duodenum. This procedure also poses minimal risk of&#xD;
        regurgitation or aspiration due to its anatomical and physiological characteristics. After&#xD;
        the procedure, the lower extremities will be elevated by about 30 degrees to prevent the&#xD;
        transplanted stool from exiting. A one-day fasting period will be maintained after the&#xD;
        procedure to facilitate successful engraftment of the transplanted stool, followed by the&#xD;
        gradual resumption of a regular diet. Following FMT, repeated rectal swab cultures will be&#xD;
        conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-7 day&#xD;
        intervals.&#xD;
  &#xD;
        In cases where encapsulated fecal material is used for FMT, it will be ingested along with&#xD;
        high-acid cranberry or orange juice. The capsules are specially designed to dissolve in&#xD;
        low-acidic environments, allowing them to reach the terminal ileum for safe administration&#xD;
        without the need for bowel preparation. On the first day, 15 capsules will be consumed,&#xD;
        followed by another 15 capsules on the second day, for a total of 30 capsules. Subsequently,&#xD;
        repeated rectal swab tests will be conducted to confirm three consecutive negative results&#xD;
        for CP-CRE or VRE at 3-day intervals.&#xD;
  &#xD;
        According to patient random allocation, fecal samples and clinical metadata will be&#xD;
        periodically collected (prior to FMT, 1 month, 3 months, 6 months, and 12 months after FMT)&#xD;
        from both recipients and donors. These collected samples will undergo full-length 16S rRNA&#xD;
        sequencing and shotgun metagenomic sequencing to comprehensively analyze the gut microbiome.&#xD;
        Through this analysis, the aim is to elucidate the intestinal microorganisms associated with&#xD;
        decolonization outcome and their mechanisms.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 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>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of Decolonization of Multidrug-Resistant Organisms at 1 Month After Fecal Microbiota Transplantation (FMT)</measure>
      <time_frame>at 1 Month After Fecal Microbiota Transplantation (FMT)</time_frame>
      <description>The decolonization rate at 1 month after FMT refers to the proportion of achieving three consecutive negative results within 1 month after the FMT procedure.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>rates of Multidrug-Resistant Organism decolonization at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)</measure>
      <time_frame>at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)</time_frame>
      <description>The decolonization rate at 1 month, 3 months, and 1 year after FMT refers to the proportion of achieving three consecutive negative results within 3 months, 6 months, and 12 months after the FMT procedure.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Post-FMT Multidrug-Resistant Organism Recolonization Rate and Infection Rate within 1 year after FMT</measure>
      <time_frame>within 12 months after FMT</time_frame>
      <description>The rates of re-colonization of decolonized multidrug-resistant organisms (CP-CRE or VRE) and clinical infection rates of MDROs within 1 year after FMT procedure.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">240</enrollment>
    <condition>Carbapenem-Resistant Enterobacteriaceae</condition>
    <condition>Vancomycin (Glycopeptide) Resistant Enterococcus (VRE)</condition>
    <arm_group>
      <arm_group_label>FMT group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>fecal microbiota transplantation using frozen or capsulized stool</description>
    </arm_group>
    <arm_group>
      <arm_group_label>non-FMT group</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Simple observation without intervention</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>fecal microbiota transplantation</intervention_name>
      <description>Fecal microbiota transplantation will be conducted on patients using donor stool (frozen or capsulized stool) from a stool bank.</description>
      <arm_group_label>FMT group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Individuals aged 20 and older.&#xD;
  &#xD;
            2. Those with confirmed carbapenemase-producing Enterobacteriaceae (CPE) from a rectal&#xD;
               swab culture within the past week (class A, B, or D CPE).&#xD;
  &#xD;
            3. Those with confirmed vancomycin-resistant Enterococci (E. fecalis or E. faecium) from&#xD;
               a rectal swab culture within the past week.&#xD;
  &#xD;
            4. Individuals who have agreed to undergo Fecal Microbiota Transplantation (FMT)&#xD;
               procedures and to provide pre- and post-procedure stool samples.&#xD;
  &#xD;
            5. Individuals who have discontinued antibiotics for a period of 3 to 7 days prior to FMT&#xD;
               procedure.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Patients with ongoing or anticipated acute treatment, including antibiotic therapy.&#xD;
  &#xD;
            2. Individuals with severe immunodeficiency.&#xD;
  &#xD;
            3. Cases where there is a risk due to upper gastrointestinal endoscopy or colonoscopy.&#xD;
  &#xD;
            4. Pregnant individuals, those who could become pregnant, and breastfeeding women.&#xD;
  &#xD;
            5. Cases where participation in the study is determined by the researcher not to be&#xD;
               beneficial.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>20 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Seung Soon Lee, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chuncheon Sacred Heart Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Seung Soon Lee, MD, PhD</last_name>
      <phone>+82-10-3379-9347</phone>
      <email>hushh93@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Jun Yong Choi, MD, PhD</last_name>
      <phone>+82-10-4073-9253</phone>
      <email>seran@yuhs.ac</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Chuncheon Sacred Heart Hospital</name>
        <address>
          <city>Chuncheon</city>
          <state>Gangwon-do</state>
          <zip>24253</zip>
          <country>Korea, Republic of</country>
        </address>
      </facility>
      <contact>
        <last_name>Seung Soon Lee, MD, PhD</last_name>
        <phone>+82-10-3379-9347</phone>
        <email>hushh93@gmail.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Severance Hospital</name>
        <address>
          <city>Seoul</city>
          <zip>03722</zip>
          <country>Korea, Republic of</country>
        </address>
      </facility>
      <contact>
        <last_name>Jun Yong Choi, MD, PhD</last_name>
        <phone>82-10-4073-9253</phone>
        <email>seran@yuhs.ac</email>
      </contact>
    </location>
    <location_countries>
      <country>Korea, Republic of</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 22, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Chuncheon Sacred Heart Hospital</investigator_affiliation>
      <investigator_full_name>Seung Soon Lee</investigator_full_name>
      <investigator_title>Associate Professor</investigator_title>
    </responsible_party>
    <keyword>Carbapenem-Resistant Enterobacteriaceae</keyword>
    <keyword>Vancomycin-Resistant Enterococci</keyword>
    <keyword>Fecal Microbiota Transplantation</keyword>
    <keyword>Gastrointestinal Microbiome</keyword>
    <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/NCT06001333
  org study id: 2023-06-007
  nct id: NCT06001333
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  The goal of this unblinded randomized controlled trial is to evaluate the efficacy and safety
        of fecal microbiota transplantation for the decolonization of carbapenemase-producing
        carbapenem-resistant Enterobacteriaceae (CP-CRE) or vancomycin-resistant Enterococci (VRE) in
        the intestinal tract. The study is planned to be conducted to test the superiority hypothesis
        that the decolonization success rate in the FMT group is higher compared to the non-FMT
        group. Outcome analysis will be conducted through intention-to-treat analysis, modified
        intention-to-treat analysis, and per-protocol analysis.
  
        The main questions it aims to answer are:
  
          -  primary endpoint: Rate of Decolonization of Multidrug-Resistant Organisms (CP-CRE or
             VRE) at 1 Month After Fecal Microbiota Transplantation (FMT).
  
          -  secondary endpoint: Rates of Multidrug-Resistant Organism decolonization at 3 months, 6
             months, and 1 year after FMT / Post-FMT Multidrug-Resistant Organism Recolonization Rate
             and Infection Rate.
  
        Patients colonized with multidrug-resistant organisms in the gastrointestinal tract are
        divided into two groups through obtaining written consent from the patients and random
        allocation: the Fecal Microbiota Transplantation group (FMT group), which receives FMT, and
        the control group (non-FMT group), which is observed without FMT. The decolonization status
        of multidrug-resistant organisms will be monitored every 3-7 days after FMT until three
        consecutive negative results.
  The study is planned to be conducted at Chuncheon Sacred Heart Hospital and Severance
        Hospital, using randomization with equal allocation to allocate patients into FMT (Fecal
        Microbiota Transplantation) and non-FMT groups. The study parameters are set with an alpha
        error of 0.05 and beta error of 0.2. Considering the findings from previous research, a delta
        value (effect size) was determined for sample size calculation. Based on this calculated
        sample size, for CP-CRE, 80 patients will be recruited in the FMT group compared to 68
        patients in the non-FMT group. For VRE, 48 patients will be recruited in the FMT group
        compared to 44 patients in the non-FMT group.
  
        Patients who have provided written consent for participation in the study will be required to
        maintain fasting starting from the evening before the procedure, after discontinuing
        broad-spectrum antibiotics for a minimum of 3-7 days. Subsequently, a bowel preparation will
        be carried out twice - the evening before and the morning of the procedure. Once the bowel
        preparation is complete, 1 hour before the procedure, patients will receive loperamide to
        reduce bowel movements and then proceed to the endoscopy suite.
  
        Fecal microbiota transplantation (FMT) will be carried out with the acquired frozen donor
        stool, which will be thawed for 2 hours at room temperature following purchase and delivery
        from a stool bank, under the consent and supervision of the patient or guardian. Frozen stool
        from carefully screened donors who have passed the rigorous screening of both Stage 1
        clinical assessment and Stage 2 laboratory tests (including evaluation for antibiotic
        resistance organisms) will be supplied from a stool bank of Microbiotix inc.
  
        The FMT procedure will be conducted in collaboration with the research team in the Division
        of Gastroenterology. During the procedure, no tissue biopsy or excessive endoscope insertion
        will be performed. The FMT involves the simple infusion of thawed donor stool into the
        terminal ileum under colonoscopy, which takes approximately 5-10 minutes. The procedure
        carries minimal risk of bleeding, perforation, or aspiration. In most cases, it will be
        performed under sedation with a colonoscopy. If smooth insertion of the colonoscope or proper
        visualization of the colon is hindered, or if colonic preparation is not successful,
        Esophagogastroduodenoscopy (EGD) will be performed with sedation, and thawed donor stool will
        be infused into the third portion of the duodenum. This procedure also poses minimal risk of
        regurgitation or aspiration due to its anatomical and physiological characteristics. After
        the procedure, the lower extremities will be elevated by about 30 degrees to prevent the
        transplanted stool from exiting. A one-day fasting period will be maintained after the
        procedure to facilitate successful engraftment of the transplanted stool, followed by the
        gradual resumption of a regular diet. Following FMT, repeated rectal swab cultures will be
        conducted to confirm three consecutive negative results for CP-CRE or VRE at 3-7 day
        intervals.
  
        In cases where encapsulated fecal material is used for FMT, it will be ingested along with
        high-acid cranberry or orange juice. The capsules are specially designed to dissolve in
        low-acidic environments, allowing them to reach the terminal ileum for safe administration
        without the need for bowel preparation. On the first day, 15 capsules will be consumed,
        followed by another 15 capsules on the second day, for a total of 30 capsules. Subsequently,
        repeated rectal swab tests will be conducted to confirm three consecutive negative results
        for CP-CRE or VRE at 3-day intervals.
  
        According to patient random allocation, fecal samples and clinical metadata will be
        periodically collected (prior to FMT, 1 month, 3 months, 6 months, and 12 months after FMT)
        from both recipients and donors. These collected samples will undergo full-length 16S rRNA
        sequencing and shotgun metagenomic sequencing to comprehensively analyze the gut microbiome.
        Through this analysis, the aim is to elucidate the intestinal microorganisms associated with
        decolonization outcome and their mechanisms.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Rate of Decolonization of Multidrug-Resistant Organisms at 1 Month After Fecal Microbiota Transplantation (FMT)
  time frame: at 1 Month After Fecal Microbiota Transplantation (FMT)
  description: The decolonization rate at 1 month after FMT refers to the proportion of achieving three consecutive negative results within 1 month after the FMT procedure.
  measure: rates of Multidrug-Resistant Organism decolonization at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)
  time frame: at 3 months, 6 months, and 1 year after Fecal Microbiota Transplantation (FMT)
  description: The decolonization rate at 1 month, 3 months, and 1 year after FMT refers to the proportion of achieving three consecutive negative results within 3 months, 6 months, and 12 months after the FMT procedure.
  measure: Post-FMT Multidrug-Resistant Organism Recolonization Rate and Infection Rate within 1 year after FMT
  time frame: within 12 months after FMT
  description: The rates of re-colonization of decolonized multidrug-resistant organisms (CP-CRE or VRE) and clinical infection rates of MDROs within 1 year after FMT procedure.
  arm group label: FMT group
  arm group type: Experimental
  description: fecal microbiota transplantation using frozen or capsulized stool
  arm group label: non-FMT group
  arm group type: No Intervention
  description: Simple observation without intervention
  intervention type: Procedure
  intervention name: fecal microbiota transplantation
  description: Fecal microbiota transplantation will be conducted on patients using donor stool (frozen or capsulized stool) from a stool bank.
  arm group label: FMT group
  criteria: 
  gender: All
  minimum age: 20 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Seung Soon Lee, MD, PhD
  role: Principal Investigator
  affiliation: Chuncheon Sacred Heart Hospital
  last name: Seung Soon Lee, MD, PhD
  phone: +82-10-3379-9347
  email: hushh93@gmail.com
  last name: Jun Yong Choi, MD, PhD
  phone: +82-10-4073-9253
  email: seran@yuhs.ac
  facility: 
  contact: 
  facility: 
  contact: 
  country: Korea, Republic of
  responsible party type: Principal Investigator
  investigator affiliation: Chuncheon Sacred Heart Hospital
  investigator full name: Seung Soon Lee
  investigator title: Associate Professor
  sharing ipd: No