<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/NCT03005379</url>
  </required_header>
  <id_info>
    <org_study_id>2004</org_study_id>
    <nct_id>NCT03005379</nct_id>
  </id_info>
  <brief_title>Microbiota or Placebo After Antimicrobial Therapy for Recurrent C. Difficile at Home (MATCH)</brief_title>
  <acronym>MATCH</acronym>
  <official_title>CSP #2004 - Microbiota or Placebo After Antimicrobial Therapy for Recurrent C. Difficile at Home (MATCH)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</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>
      The purpose of this study is to determine whether Fecal Microbiota Therapy (FMT) is effective&#xD;
      vs. placebo in the prevention of C. difficile infection recurrence.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Clostridium difficile infection (CDI) is one of the most common nosocomial infections and is&#xD;
      increasingly seen in non-hospitalized patients. Although more than 90% of patients have&#xD;
      symptom resolution with a course of standard antimicrobial therapy, subsequent recurrence&#xD;
      rates range from 15-30% (after the first CDI episode) to 40-50% (after the second and&#xD;
      subsequent episodes). Fecal microbiota transplantation (FMT) has shown promise as an adjunct&#xD;
      to standard antimicrobial therapy, reducing recurrence among FMT recipients to 15%.&#xD;
&#xD;
      The primary study goal is to assess the efficacy of FMT for the prevention of subsequent&#xD;
      recurrent CDI, when administered after successful treatment of recurrent CDI with standard&#xD;
      antimicrobial therapy. Secondary goals are to evaluate, the efficacy of FMT in terms of CDI&#xD;
      severity, duration, the safety of FMT, and in the event of a positive study result, establish&#xD;
      a mechanism for providing FMT within the VA system.&#xD;
&#xD;
      This study will enroll 390 participants. Participants will be randomized (1:1 ratio) to FMT&#xD;
      or placebo, stratified by number of prior recurrent CDI episodes (1 versus &gt;1). They will be&#xD;
      assessed for symptoms of CDI, other study outcomes and any treatment-related adverse events&#xD;
      at 2, 14, 28, 42, and 56 days, and month 3, 4, 5 and 6 after administration of the study&#xD;
      treatment.&#xD;
&#xD;
      The primary outcome is recurrent CDI (definite or possible) or death within 56 days of&#xD;
      randomization.&#xD;
&#xD;
      Definite recurrence is defined as any of the following: The new onset of more than three&#xD;
      loose or watery stools in 24 hours for two consecutive days, not explained by another&#xD;
      diagnosis; Other clinical symptoms including ileus, toxic megacolon, or colectomy; PLUS&#xD;
      Laboratory confirmation of C. difficile from a stool specimen by EIA toxin test. Possible&#xD;
      recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory&#xD;
      confirmation of C. difficile (stool test not sent, negative EIA toxin test result, or&#xD;
      uninterpretable result).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study is terminated for futility per protocol-specified interim analysis and DMC&#xD;
    recommendation.&#xD;
  </why_stopped>
  <start_date type="Actual">November 15, 2018</start_date>
  <completion_date type="Actual">January 31, 2023</completion_date>
  <primary_completion_date type="Actual">August 30, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrent CDI (definite or probable) or death</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>The primary outcome is recurrent CDI (definite or probable) or death within 56 days of randomization.&#xD;
Definite recurrence is defined as any of the following:&#xD;
The new onset of more than three loose or watery stools in 24 hours for two consecutive days&#xD;
Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS&#xD;
Laboratory confirmation of C. difficile from a stool specimen.&#xD;
Probable recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrent CDI (definite or possible), or death</measure>
    <time_frame>Within 6 months of randomization</time_frame>
    <description>The incidence of recurrent CDI (definite or possible) or death within 6 months of randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life</measure>
    <time_frame>56 days from randomization</time_frame>
    <description>The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of CDI recurrences</measure>
    <time_frame>Within 6 months of randomization</time_frame>
    <description>The number of CDI recurrences within 6 months for a patient is the count of separate CDI recurrences from randomization to 6 months after randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diarrhea that is negative for C. difficile by EIA toxin test and PCR</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>This is similar to probable recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test and PCR, not episodes that are not tested or are uninterpretable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple related symptoms</measure>
    <time_frame>Within 6 months of randomization</time_frame>
    <description>An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Definite recurrent CDI</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>The incidence of definite recurrent CDI within 56 days of randomization. Definite recurrence is defined as any of the following:&#xD;
The new onset of more than three loose or watery stools in 24 hours for two consecutive days&#xD;
Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS&#xD;
Laboratory confirmation of C. difficile from a stool specimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Possible recurrent CDI</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>The incidence of probable recurrent CDI within 56 days of randomization. Possible recurrence is defined as the same clinical manifestations as definite recurrent CDI, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>The incidence of death within 56 days of randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diarrhea that is negative for C. difficile by EIA toxin testing but positive by PCR</measure>
    <time_frame>Within 56 days of randomization</time_frame>
    <description>This is similar to possible recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test, not episodes that are not tested or are uninterpretable.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse and Serious Adverse Events</measure>
    <time_frame>Within 6 months of randomization</time_frame>
    <description>Safety outcomes to be collected include:&#xD;
Serious adverse events, with a focus on SAEs involving hospitalization (new or prolonged), and all-cause mortality&#xD;
Adverse events which may be related to FMT treatment. This includes adverse events which Site Investigators consider related/possibly related to the study treatment and all adverse events which occur within 14 days of study treatment (since an aggregate analysis of events temporally linked to treatment could show a causal relationship when compared to placebo)&#xD;
Infectious transmissions which are plausibly linked to FMT treatment.&#xD;
Development of new conditions theoretically linked to alterations in gut microbiota.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">153</enrollment>
  <condition>Clostridium Difficile Infection</condition>
  <arm_group>
    <arm_group_label>1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fecal Microbiota Therapy (FMT)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fecal Microbiota Therapy (FMT)</intervention_name>
    <description>Oral capsule-delivered FMT</description>
    <arm_group_label>1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Oral capsule-delivered placebo</description>
    <arm_group_label>2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. One or more episodes recurrent CDI (defined as &gt; 3 loose/watery stools/24h for 2&#xD;
             consecutive days with CDI treatment, and not explained by another diagnosis PLUS&#xD;
             laboratory confirmation of C. difficile; or ileus, or toxic megacolon PLUS laboratory&#xD;
             confirmation of C. difficile, occurring within 90 days of a prior CDI episode with&#xD;
             similar symptoms and laboratory confirmation)&#xD;
&#xD;
          2. Resolution or improvement of symptoms from most recent CDI episode, defined as no&#xD;
             longer meeting the clinical definition for CDI for a 48 hour period during treatment,&#xD;
             including not meeting the definition again after an initial improvement&#xD;
&#xD;
          3. Within the enrollment window: 2 days after completion of antimicrobial therapy for CDI&#xD;
             (to allow for a washout period) to 14 days after completion of therapy or 30 days&#xD;
             after the onset of CDI whichever is later.&#xD;
&#xD;
          4. Age 18 years&#xD;
&#xD;
          5. Enrolled in a VHA facility&#xD;
&#xD;
          6. Able and willing to provide informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unlikely to swallow capsules&#xD;
&#xD;
          2. Pregnancy, planning to be pregnant, or breastfeeding&#xD;
&#xD;
          3. Receipt of cytotoxic chemotherapy, intravenous or subcutaneous immune globulin, or&#xD;
             confirmed neutropenia (absolute neutrophil count of &lt; 1,000 cells/ L) within the past&#xD;
             3 months&#xD;
&#xD;
          4. Inflammatory bowel disease or other chronic diarrheal disease/fecal incontinence&#xD;
             predating CDI&#xD;
&#xD;
          5. Ongoing antibiotic use other than those for the current episode of CDI&#xD;
&#xD;
          6. Prior FMT&#xD;
&#xD;
          7. Life expectancy of &lt; 8 weeks&#xD;
&#xD;
          8. Anaphylactic food allergy&#xD;
&#xD;
          9. Active enrollment in another research study on antibiotics, probiotics, or FMT without&#xD;
             investigators approval&#xD;
&#xD;
         10. Presence of an ileostomy or colostomy&#xD;
&#xD;
         11. HIV with CD4 count &lt; 200 cells/�L in prior 3 months&#xD;
&#xD;
         12. Decompensated cirrhosis&#xD;
&#xD;
         13. Bone marrow/peripheral blood stem cell transplant in the past year&#xD;
&#xD;
         14. Unlikely to follow study protocol&#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>Dimitri M Drekonja, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Minneapolis VA Health Care System, Minneapolis, MN</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Aasma Shaukat, MD MPH</last_name>
    <role>Study Chair</role>
    <affiliation>Minneapolis VA Health Care System, Minneapolis, MN</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Minneapolis VA Health Care System, Minneapolis, MN</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55417-2309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Drekonja DM, Shaukat A, Zhang JH, Reinink AR, Nugent S, Dominitz JA, Davis-Karim A, Gerding DN, Kyriakides TC. Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment. Clin Trials. 2021 Oct;18(5):622-629. doi: 10.1177/17407745211021198. Epub 2021 Jun 22.</citation>
    <PMID>34154439</PMID>
  </results_reference>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 29, 2016</study_first_posted>
  <last_update_submitted>February 3, 2023</last_update_submitted>
  <last_update_submitted_qc>February 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FMT</keyword>
  <keyword>recurrent c. difficile</keyword>
  <keyword>infectious disease</keyword>
  <keyword>intestine</keyword>
  <keyword>clinical trial</keyword>
  <keyword>gastrointestinal</keyword>
  <keyword>prevention</keyword>
  <keyword>randomized</keyword>
  <keyword>diarrhea</keyword>
  <keyword>fecal microbiota therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Digital data underlying primary scientific publications from this study will be held as part of a data sharing resource maintained by the Cooperative Studies Program (CSP). Study data held for this purpose may include data, data content, format, and organization. The data may be available to the public and other VA and non-VA researchers under certain conditions and consistent with the informed consent and CSP policy which prioritize protecting subjects' privacy and confidentiality to the fullest extent possible.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
  </patient_data>
  <pending_results>
    <submitted>August 23, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03005379
org study id: 2004
nct id: NCT03005379
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study is to determine whether Fecal Microbiota Therapy (FMT) is effective
      vs. placebo in the prevention of C. difficile infection recurrence.
Clostridium difficile infection (CDI) is one of the most common nosocomial infections and is
      increasingly seen in non-hospitalized patients. Although more than 90% of patients have
      symptom resolution with a course of standard antimicrobial therapy, subsequent recurrence
      rates range from 15-30% (after the first CDI episode) to 40-50% (after the second and
      subsequent episodes). Fecal microbiota transplantation (FMT) has shown promise as an adjunct
      to standard antimicrobial therapy, reducing recurrence among FMT recipients to 15%.

      The primary study goal is to assess the efficacy of FMT for the prevention of subsequent
      recurrent CDI, when administered after successful treatment of recurrent CDI with standard
      antimicrobial therapy. Secondary goals are to evaluate, the efficacy of FMT in terms of CDI
      severity, duration, the safety of FMT, and in the event of a positive study result, establish
      a mechanism for providing FMT within the VA system.

      This study will enroll 390 participants. Participants will be randomized (1:1 ratio) to FMT
      or placebo, stratified by number of prior recurrent CDI episodes (1 versus >1). They will be
      assessed for symptoms of CDI, other study outcomes and any treatment-related adverse events
      at 2, 14, 28, 42, and 56 days, and month 3, 4, 5 and 6 after administration of the study
      treatment.

      The primary outcome is recurrent CDI (definite or possible) or death within 56 days of
      randomization.

      Definite recurrence is defined as any of the following: The new onset of more than three
      loose or watery stools in 24 hours for two consecutive days, not explained by another
      diagnosis; Other clinical symptoms including ileus, toxic megacolon, or colectomy; PLUS
      Laboratory confirmation of C. difficile from a stool specimen by EIA toxin test. Possible
      recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory
      confirmation of C. difficile (stool test not sent, negative EIA toxin test result, or
      uninterpretable result).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Triple (Participant, Care Provider, Investigator)
measure: Recurrent CDI (definite or probable) or death
time frame: Within 56 days of randomization
description: The primary outcome is recurrent CDI (definite or probable) or death within 56 days of randomization.
Definite recurrence is defined as any of the following:
The new onset of more than three loose or watery stools in 24 hours for two consecutive days
Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS
Laboratory confirmation of C. difficile from a stool specimen.
Probable recurrence is defined as the same clinical manifestations as above, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).
measure: Recurrent CDI (definite or possible), or death
time frame: Within 6 months of randomization
description: The incidence of recurrent CDI (definite or possible) or death within 6 months of randomization.
measure: Quality of Life
time frame: 56 days from randomization
description: The investigators will use a brief assessment of both overall and gastrointestinal health status, using a previously validated instrument.
measure: Number of CDI recurrences
time frame: Within 6 months of randomization
description: The number of CDI recurrences within 6 months for a patient is the count of separate CDI recurrences from randomization to 6 months after randomization.
measure: Diarrhea that is negative for C. difficile by EIA toxin test and PCR
time frame: Within 56 days of randomization
description: This is similar to probable recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test and PCR, not episodes that are not tested or are uninterpretable.
measure: Multiple related symptoms
time frame: Within 6 months of randomization
description: An assessment for non-diarrheal manifestations of CDI such as abdominal pain, urgency, and fecal incontinence will be performed.
measure: Definite recurrent CDI
time frame: Within 56 days of randomization
description: The incidence of definite recurrent CDI within 56 days of randomization. Definite recurrence is defined as any of the following:
The new onset of more than three loose or watery stools in 24 hours for two consecutive days
Other clinical symptoms including ileus, toxic mega colon, or colectomy PLUS
Laboratory confirmation of C. difficile from a stool specimen.
measure: Possible recurrent CDI
time frame: Within 56 days of randomization
description: The incidence of probable recurrent CDI within 56 days of randomization. Possible recurrence is defined as the same clinical manifestations as definite recurrent CDI, but WITHOUT laboratory confirmation of C. difficile (stool test not sent, negative result, or uninterpretable result).
measure: Death
time frame: Within 56 days of randomization
description: The incidence of death within 56 days of randomization.
measure: Diarrhea that is negative for C. difficile by EIA toxin testing but positive by PCR
time frame: Within 56 days of randomization
description: This is similar to possible recurrent CDI, but includes only episodes of diarrhea that test negative for C. difficile by EIA toxin test, not episodes that are not tested or are uninterpretable.
measure: Adverse and Serious Adverse Events
time frame: Within 6 months of randomization
description: Safety outcomes to be collected include:
Serious adverse events, with a focus on SAEs involving hospitalization (new or prolonged), and all-cause mortality
Adverse events which may be related to FMT treatment. This includes adverse events which Site Investigators consider related/possibly related to the study treatment and all adverse events which occur within 14 days of study treatment (since an aggregate analysis of events temporally linked to treatment could show a causal relationship when compared to placebo)
Infectious transmissions which are plausibly linked to FMT treatment.
Development of new conditions theoretically linked to alterations in gut microbiota.
arm group label: 1
arm group type: Active Comparator
description: Fecal Microbiota Therapy (FMT)
arm group label: 2
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: Fecal Microbiota Therapy (FMT)
description: Oral capsule-delivered FMT
arm group label: 1
intervention type: Drug
intervention name: Placebo
description: Oral capsule-delivered placebo
arm group label: 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dimitri M Drekonja, MD
role: Study Chair
affiliation: Minneapolis VA Health Care System, Minneapolis, MN
last name: Aasma Shaukat, MD MPH
role: Study Chair
affiliation: Minneapolis VA Health Care System, Minneapolis, MN
facility: 
country: United States
citation: Drekonja DM, Shaukat A, Zhang JH, Reinink AR, Nugent S, Dominitz JA, Davis-Karim A, Gerding DN, Kyriakides TC. Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment. Clin Trials. 2021 Oct;18(5):622-629. doi: 10.1177/17407745211021198. Epub 2021 Jun 22.
PMID: 34154439
responsible party type: Sponsor
mesh term: Clostridium Infections
sharing ipd: Yes
ipd description: Digital data underlying primary scientific publications from this study will be held as part of a data sharing resource maintained by the Cooperative Studies Program (CSP). Study data held for this purpose may include data, data content, format, and organization. The data may be available to the public and other VA and non-VA researchers under certain conditions and consistent with the informed consent and CSP policy which prioritize protecting subjects' privacy and confidentiality to the fullest extent possible.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
submitted: August 23, 2023