<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/NCT03806803</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00087406</org_study_id>
    <nct_id>NCT03806803</nct_id>
  </id_info>
  <brief_title>Multicentre Blinded Comparison of Lyophilized Sterile Fecal Filtrate to Lyophilized Fecal Microbiota Transplant in Recurrent Clostridioides Difficile Infection</brief_title>
  <official_title>A Multicenter Double Blind Randomized Study Comparing the Efficacy of Lyophilized Sterile Fecal Filtrate to Lyophilized Fecal Microbiota Transplantation (FMT) in the Management of Recurrent Clostridioides Difficile Infection (CDI)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of British Columbia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>McGill University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Alberta</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Fecal microbiota transplantation (FMT) is a treatment that restores the balance of gut&#xD;
      bacteria and is the most effective treatment for patients who suffer from recurrent&#xD;
      Clostridioides difficile infection (CDI) brought on by antibiotic use. Although highly&#xD;
      effective, we do not understand how FMT actually works.&#xD;
&#xD;
      Freeze-dried or lyophilized fecal microbiota transplant (LFMT) has been shown to be&#xD;
      effective. Recently, filtered fecal slurry, free of any live bacteria, has also been shown to&#xD;
      cure 5 such patients. The advantage of the filtered fecal slurry is that it may be safer to&#xD;
      patients as it does not contain any live bacteria. We have conducted a pilot study comparing&#xD;
      LFMT to lyophilized sterile fecal filtrate (LSFF) in 9 patients, and found that the success&#xD;
      rate of treatment was 80% vs 75% in these 2 groups.&#xD;
&#xD;
      Therefore we need to perform a larger multicenter study to compare LFMT to LSFF to determine&#xD;
      the success rate of curing these patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This prospective double blind randomized study will enroll 248 patients with recurrent&#xD;
      Clostridium difficile infection (RCDI) in a 1:1 ratio to receive either LFMT or LSFF by&#xD;
      capsules.&#xD;
&#xD;
      Patients will receive 15 capsules at week 0 and be assessed at weeks 1, 4, 8 and 24. Blood,&#xD;
      stool and urine samples will be collected. If the first treatment fails, patients will be&#xD;
      given open label LFMT from the same donor. If treatment fails again, FMT will be offered in&#xD;
      the form and route at the treating physician's discretion.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 21, 2019</start_date>
  <completion_date type="Anticipated">June 2026</completion_date>
  <primary_completion_date type="Anticipated">December 2025</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>
    <intervention_model_description>double blind randomized</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>LFMT and LSFF appear identical. Randomization is performed by lab staff not involved in any aspect of treatment administration or care.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Resolution of RCDI</measure>
    <time_frame>8 weeks</time_frame>
    <description>Proportion of patients without RCDI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Resolution of RCDI</measure>
    <time_frame>24 weeks</time_frame>
    <description>Proportion of patients with sustained cure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>8 weeks</time_frame>
    <description>Mortality directly attributable to CDI or treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serious Adverse Events</measure>
    <time_frame>8 weeks</time_frame>
    <description>Infection directly attributable to treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor Adverse Events</measure>
    <time_frame>1 week</time_frame>
    <description>Nausea</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor Adverse Events</measure>
    <time_frame>1 week</time_frame>
    <description>Vomiting</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minor Adverse Events</measure>
    <time_frame>1 week</time_frame>
    <description>Abdominal discomfort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difficulty swallowing capsules</measure>
    <time_frame>1 week</time_frame>
    <description>Reported by patients as ranging between none, moderate or severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fever</measure>
    <time_frame>1 week</time_frame>
    <description>Temperature of &gt;37.8C</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">248</enrollment>
  <condition>Clostridia Difficile Colitis</condition>
  <condition>Clostridium Difficile Diarrhea</condition>
  <arm_group>
    <arm_group_label>LFMT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lyophilized fecal microbiota transplant capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LSFF</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Lyophilized sterile fecal filtrate capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Lyophilized fecal microbiota transplant</intervention_name>
    <description>15 capsules</description>
    <arm_group_label>LFMT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Lyophilized sterile fecal filtrate</intervention_name>
    <description>15 capsules</description>
    <arm_group_label>LSFF</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  at least 3 episodes of recurrent CDI with each episode defined as 3 or more unformed&#xD;
             stools in 24 hours associated with positive Clostridium difficile test, each occurring&#xD;
             within 3 months of each other.&#xD;
&#xD;
          -  CDI infection under symptomatic control with 3 or fewer unformed stools in 24 hours&#xD;
             for at least 2 consecutive days prior to treatment&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
          -  Females and males must agree to effective contraception for the duration of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe or fulminant colitis&#xD;
&#xD;
          -  Chronic diarrheal illnesses such as irritable bowel syndrome or inflammatory bowel&#xD;
             disease unless under control or in remission 3 months prior to enrollment.&#xD;
&#xD;
          -  Those taking or planning to take an investigational drug within 3 months of enrollment&#xD;
&#xD;
          -  Chemotherapy or radiation therapy&#xD;
&#xD;
          -  Oropharyngeal or significant esophageal dysphagia&#xD;
&#xD;
          -  Ileus or small bowel obstruction&#xD;
&#xD;
          -  Pregnant or planning to become pregnant within 3 months&#xD;
&#xD;
          -  Breastfeeding or planning to breastfeed during the trial&#xD;
&#xD;
          -  Active infection requiring antibiotics&#xD;
&#xD;
          -  Life expectancy &lt;6 months Those with history of total colectomy&#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>Dina Kao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Alberta</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Dina Kao, MD</last_name>
    <phone>780 492 8307</phone>
    <email>dkao@ualberta.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Alberta Hospital</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2X8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dina Kao, MD</last_name>
      <phone>780 492 8307</phone>
      <email>dkao@ualberta.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ted Steiner, MD</last_name>
      <phone>604-875-4111</phone>
      <phone_ext>68492</phone_ext>
      <email>tsteiner@mail.ubc.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of British Columbia</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <zip>V8R 1J8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Christine Lee, MD</last_name>
      <phone>250-519-1895</phone>
      <email>christine.lee@islandhealth.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Mcgill University Health Centre</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vivian Loo, MD</last_name>
      <phone>514-934-1934</phone>
      <phone_ext>42818</phone_ext>
      <email>vivan.loo@mcgill.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University Of Calgary</name>
      <address>
        <city>Calgary</city>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Thomas Louie, MD</last_name>
      <phone>403-944-2038</phone>
      <email>thomas.louie@albertahealthservices.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>June 2, 2023</last_update_submitted>
  <last_update_submitted_qc>June 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clostridium Infections</mesh_term>
    <mesh_term>Diarrhea</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03806803
org study id: Pro00087406
nct id: NCT03806803
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Fecal microbiota transplantation (FMT) is a treatment that restores the balance of gut
      bacteria and is the most effective treatment for patients who suffer from recurrent
      Clostridioides difficile infection (CDI) brought on by antibiotic use. Although highly
      effective, we do not understand how FMT actually works.

      Freeze-dried or lyophilized fecal microbiota transplant (LFMT) has been shown to be
      effective. Recently, filtered fecal slurry, free of any live bacteria, has also been shown to
      cure 5 such patients. The advantage of the filtered fecal slurry is that it may be safer to
      patients as it does not contain any live bacteria. We have conducted a pilot study comparing
      LFMT to lyophilized sterile fecal filtrate (LSFF) in 9 patients, and found that the success
      rate of treatment was 80% vs 75% in these 2 groups.

      Therefore we need to perform a larger multicenter study to compare LFMT to LSFF to determine
      the success rate of curing these patients.
This prospective double blind randomized study will enroll 248 patients with recurrent
      Clostridium difficile infection (RCDI) in a 1:1 ratio to receive either LFMT or LSFF by
      capsules.

      Patients will receive 15 capsules at week 0 and be assessed at weeks 1, 4, 8 and 24. Blood,
      stool and urine samples will be collected. If the first treatment fails, patients will be
      given open label LFMT from the same donor. If treatment fails again, FMT will be offered in
      the form and route at the treating physician's discretion.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: double blind randomized
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: LFMT and LSFF appear identical. Randomization is performed by lab staff not involved in any aspect of treatment administration or care.
measure: Resolution of RCDI
time frame: 8 weeks
description: Proportion of patients without RCDI
measure: Resolution of RCDI
time frame: 24 weeks
description: Proportion of patients with sustained cure
measure: Serious Adverse Events
time frame: 8 weeks
description: Mortality directly attributable to CDI or treatment
measure: Serious Adverse Events
time frame: 8 weeks
description: Infection directly attributable to treatment
measure: Minor Adverse Events
time frame: 1 week
description: Nausea
measure: Minor Adverse Events
time frame: 1 week
description: Vomiting
measure: Minor Adverse Events
time frame: 1 week
description: Abdominal discomfort
measure: Difficulty swallowing capsules
time frame: 1 week
description: Reported by patients as ranging between none, moderate or severe
measure: Fever
time frame: 1 week
description: Temperature of >37.8C
arm group label: LFMT
arm group type: Active Comparator
description: Lyophilized fecal microbiota transplant capsules
arm group label: LSFF
arm group type: Experimental
description: Lyophilized sterile fecal filtrate capsules
intervention type: Biological
intervention name: Lyophilized fecal microbiota transplant
description: 15 capsules
arm group label: LFMT
intervention type: Biological
intervention name: Lyophilized sterile fecal filtrate
description: 15 capsules
arm group label: LSFF
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dina Kao, MD
role: Principal Investigator
affiliation: University of Alberta
last name: Dina Kao, MD
phone: 780 492 8307
email: dkao@ualberta.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Sponsor
mesh term: Clostridium Infections
mesh term: Diarrhea
sharing ipd: No