<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/NCT03796650</url>
  </required_header>
  <id_info>
    <org_study_id>COLONIZE</org_study_id>
    <nct_id>NCT03796650</nct_id>
  </id_info>
  <brief_title>Fecal Transplantation for Primary Clostridium Difficile Infection</brief_title>
  <acronym>COLONIZE</acronym>
  <official_title>COmparative Effectiveness of intestinaL microbiOta Versus vaNcomycin for Primary c. Difficile Infection - randomiZEd Trials</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oslo University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>South-Eastern Norway Regional Health Authority</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital of North Norway</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Haukeland University Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helse Nord-Trøndelag HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vestre Viken Hospital Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Hospital of Vestfold</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sykehuset Telemark</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Alesund Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital, Akershus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lovisenberg Diakonale Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sorlandet Hospital HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ostfold Hospital Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Diakonhjemmet Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nordlandssykehuset HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sykehuset Innlandet HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Helse Stavanger HF</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Oslo University Hospital</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this randomized controlled trial the investigators want to compare the effect of one-time&#xD;
      rectal instillation of fecal microbiota transplantation, compared to a ten-day antibiotic&#xD;
      course for the treatment of primary Clostridium difficile infection (CDI). The investigators&#xD;
      hypothetsize that the instillation of feces from a healthy donor will be non-inferior to&#xD;
      vancomycin in inducing a durable cure.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Up to one third of patients with clostridium difficile infection treated with antibiotics&#xD;
      experience recurrent or relapsing symptoms within a few weeks. Even with subsequent&#xD;
      antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota&#xD;
      transplantation (FMT) has been shown to be significantly more effective in curing recurrent&#xD;
      CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment&#xD;
      option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation&#xD;
      of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen&#xD;
      transmittance and the process of finding a donor and screen for communicable disease.&#xD;
&#xD;
      The effect of FMT for recurrent CDI, however, suggests that this therapy may be more&#xD;
      effective than antibiotics in inducing a durable cure also for primary CDI. If the&#xD;
      therapeutic effect of FMT proves to be equal (non-inferior) or more effective than&#xD;
      antibiotics, FMT may be the preferable treatment option due to favourable ecological impact&#xD;
      compared to antibiotics. In an era with increasing concerns about overuse of antibiotics and&#xD;
      emergence of antibiotic resistant bacteria, it is important to investigate therapeutic&#xD;
      alternatives that may reduce the need for antibiotics.&#xD;
&#xD;
      This trial is a phase III multicentre, randomized controlled, open-label non-inferiority&#xD;
      parallel group trial with two arms (FMT and antibiotics), and is a continuation of the phase&#xD;
      II trial IMT for Primary Clostridium Difficile Infection (NCT02301000). In the current trial,&#xD;
      patients with Clostridium difficile infection and no previous CDI within 12 months prior to&#xD;
      inclusion will be randomized 1:1 to FMT or 10 days of guideline-recommended antibiotic&#xD;
      therapy (vancomycin 125 mg four times a day).&#xD;
&#xD;
      Patients are recruited in Norwegian hospitals.&#xD;
&#xD;
      The investigators plan to use frozen microbiota, because supply is easier to organize,&#xD;
      compared to fresh fecal samples. Patients in the FMT treatment group will receive one rectal&#xD;
      dose of FMT, originating from screened, healthy donors. Patients who are not cured by the&#xD;
      first dose is offered a protocol defined additional FMT treatment. In the case of clinical&#xD;
      deterioration, appropriate measures will be undertaken according to current guidelines.&#xD;
&#xD;
      Patient treatment outcomes are evaluated after 14, 60 and 365 days from inclusion and&#xD;
      treatment initiation.&#xD;
&#xD;
      An interim analysis is planned after inclusion of the first 94 patients (corresponding to 50%&#xD;
      of the planned number of patients).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 17, 2019</start_date>
  <completion_date type="Anticipated">January 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 31, 2024</primary_completion_date>
  <phase>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>
    <intervention_model_description>Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>An open-label, partly assessor blinded trial.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Patients with durable cure</measure>
    <time_frame>60 days</time_frame>
    <description>Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with the assigned treatment alone.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Patients with durable cure with additional treatment.</measure>
    <time_frame>60 days</time_frame>
    <description>Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with or without the need of additional treatment (FMT, metronidazole or vancomycin).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment adverse events</measure>
    <time_frame>60 and 365 days</time_frame>
    <description>Proportion of patients with adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients with long-time cure</measure>
    <time_frame>365 days</time_frame>
    <description>Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, and without recurrent C. difficile infection within 365 days after treatment start.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health-economic evaluation</measure>
    <time_frame>365 days</time_frame>
    <description>Health-economic analysis of the two compared treatment modalities</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Fecal composition and treatment outcome</measure>
    <time_frame>60 days</time_frame>
    <description>Correlation in fecal composition changes before versus after treatment, and treatment outcome (such as bacterial diversity and fecal short chain fatty acids).&#xD;
Subgroup analyses will be performed for sex, age, co-morbidities, and FMT donor.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">188</enrollment>
  <condition>Clostridium Difficile Infection</condition>
  <arm_group>
    <arm_group_label>Fecal microbiota transplantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Fecal microbiota from healthy, screened stool donors at the University Hospital of North Norway. Patients will receive one FMT enema immediately after enrolment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antibiotic treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients randomized to the control group will receive a ten-day course of oral vancomycin four times a day. This is according to international guidelines for primary C. difficile treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Fecal microbiota transplantation</intervention_name>
    <description>50 g donor feces suspended in saline with added glycerol, administered by a enema kit.</description>
    <arm_group_label>Fecal microbiota transplantation</arm_group_label>
    <other_name>FMT</other_name>
    <other_name>IMT</other_name>
    <other_name>Bacteriotherapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vancomycin</intervention_name>
    <description>Peroral vancomycin 125 mg q.i.d. for ten days.</description>
    <arm_group_label>Antibiotic treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients, ≥18 years with primary C. difficile infection, defined by the following&#xD;
             three criteria:&#xD;
&#xD;
               1. Diarrhea as defined by the WHO (≥3 loose stools per day), and&#xD;
&#xD;
               2. Positive stool test for toxin producing C. difficile, and&#xD;
&#xD;
               3. No evidence of previous C. difficile infection during 365 days before enrolment.&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known presence of other stool pathogens known to cause diarrhea.&#xD;
&#xD;
          -  Ongoing antibiotic treatment for other infections that cannot be stopped before study&#xD;
             treatment administration.&#xD;
&#xD;
          -  Inflammatory bowel disease or microscopic colitis.&#xD;
&#xD;
          -  &lt; 3 months life expectancy.&#xD;
&#xD;
          -  Serious immunodeficiency, defined as one of the following:&#xD;
&#xD;
               -  Ongoing or recent chemotherapy and current or expected neutropenia with&#xD;
                  neutrophil count of &lt; 500/μL.&#xD;
&#xD;
               -  Active severe immunocompromising disease.&#xD;
&#xD;
          -  Inability to comply with protocol requirements.&#xD;
&#xD;
          -  Need of intensive care.&#xD;
&#xD;
          -  Known irritable bowel syndrome, diarrheal type.&#xD;
&#xD;
          -  Pregnancy or nursing.&#xD;
&#xD;
          -  Known or suspected toxic megacolon or ileus.&#xD;
&#xD;
          -  Total or subtotal colectomy, ileostomy or colonostomy.&#xD;
&#xD;
          -  Contraindications for rectal catheter insertion&#xD;
&#xD;
          -  Known hypersensitivity or other contraindications to vancomycin&#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>Michael Bretthauer, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Oslo Universitetssykehus HF, Rikshospitalet</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Kjetil Garborg, MD, PhD</last_name>
    <phone>+4741578975</phone>
    <email>k.k.garborg@medisin.uio.no</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Frederik Emil Juul, MD</last_name>
    <phone>+4797512966</phone>
    <email>f.e.juul@medisin.uio.no</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Vestre Viken HF, Bærum Hospital</name>
      <address>
        <city>Sandvika</city>
        <state>Gjettum</state>
        <zip>1346</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Øystein Rose, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Haukeland universitetssykehus</name>
      <address>
        <city>Bergen</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Trygve Hausken, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nordlandssykehuset</name>
      <address>
        <city>Bodø</city>
        <zip>8092</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eirik H Ofstad, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sykehuset Østfold Kalnes</name>
      <address>
        <city>Grålum</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jon Birger Haug, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UNN Harstad</name>
      <address>
        <city>Harstad</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter H. Johnsen, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sørlandet Hospital HF</name>
      <address>
        <city>Kristiansand</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Håvard Wiig, MD</last_name>
    </contact>
    <investigator>
      <last_name>Rita Helleren, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sykehuset Levanger</name>
      <address>
        <city>Levanger</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eivind Ness-Jensen, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sykehuset Innlandet HF</name>
      <address>
        <city>Lillehammer</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ragnhild Eiken, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Akershus University Hospital</name>
      <address>
        <city>Lørenskog</city>
        <zip>1478</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jan Erik Berdal, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Diakonhjemmet Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0319</zip>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Raziye B. Cetinkaya, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Lovisenberg sykehus</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jørgen Valeur, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital Rikshospitalet</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frederik Emil Juul, MD</last_name>
      <email>f.e.juul@medisin.uio.no</email>
    </contact>
    <contact_backup>
      <last_name>Siv Elisabeth Isaksen</last_name>
    </contact_backup>
    <investigator>
      <last_name>Kjetil Garborg, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital Ullevål</name>
      <address>
        <city>Oslo</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristian Tonby, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>Frederik Emil Juul, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Telemark Hospital HF</name>
      <address>
        <city>Skien</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Pavel Gudkov, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Stavanger University Hospital</name>
      <address>
        <city>Stavanger</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Trond J Cooper, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UNN Tromsø</name>
      <address>
        <city>Tromsø</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rasmus Goll, MD, PhD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Sykehuset i Vestfold</name>
      <address>
        <city>Tønsberg</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Awet Abraham, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Ålesund Sjukehus</name>
      <address>
        <city>Ålesund</city>
        <country>Norway</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dag Arne Lihaug Hoff, MD, PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Norway</country>
  </location_countries>
  <link>
    <url>https://www.med.uio.no/helsam/english/research/groups/clinical-effectiveness/index.html</url>
    <description>Investigating research group' home page</description>
  </link>
  <reference>
    <citation>McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.</citation>
    <PMID>29562266</PMID>
  </reference>
  <reference>
    <citation>Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.</citation>
    <PMID>29860912</PMID>
  </reference>
  <reference>
    <citation>Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015 Apr 16;372(16):1539-48. doi: 10.1056/NEJMra1403772. No abstract available.</citation>
    <PMID>25875259</PMID>
  </reference>
  <reference>
    <citation>van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2145. doi: 10.1056/NEJMc1303919. No abstract available.</citation>
    <PMID>23718168</PMID>
  </reference>
  <reference>
    <citation>Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013 Apr;108(4):500-8. doi: 10.1038/ajg.2013.59. Epub 2013 Mar 19.</citation>
    <PMID>23511459</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <last_update_submitted>April 22, 2022</last_update_submitted>
  <last_update_submitted_qc>April 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oslo University Hospital</investigator_affiliation>
    <investigator_full_name>Kjetil Garborg</investigator_full_name>
    <investigator_title>Joint Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Clostridium difficile</keyword>
  <keyword>Intestinal microbiota therapy</keyword>
  <keyword>Fecal microbiota transplantation</keyword>
  <keyword>Investigator-initiated</keyword>
  <keyword>Antibiotics</keyword>
  <keyword>Diarrhea</keyword>
  <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>Clostridium Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vancomycin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>The trial adheres to data sharing policies of the ICMJE. Data sharing is considered for each request by the principal investigators. Data sharing is not granted if they overlap with planned analyses. Data sharing requires all approvals by relevant authorities. Costs for data sharing will not be covered by the study group.</ipd_description>
  </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/NCT03796650
org study id: COLONIZE
nct id: NCT03796650
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has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
In this randomized controlled trial the investigators want to compare the effect of one-time
      rectal instillation of fecal microbiota transplantation, compared to a ten-day antibiotic
      course for the treatment of primary Clostridium difficile infection (CDI). The investigators
      hypothetsize that the instillation of feces from a healthy donor will be non-inferior to
      vancomycin in inducing a durable cure.
Up to one third of patients with clostridium difficile infection treated with antibiotics
      experience recurrent or relapsing symptoms within a few weeks. Even with subsequent
      antibiotic treatment, multiple recurrences/relapses are frequent. Fecal microbiota
      transplantation (FMT) has been shown to be significantly more effective in curing recurrent
      CDI than repeated antibiotic treatment. In current guidelines, FMT is proposed as a treatment
      option after multiple recurrences/relapses of CDI. The rationale to reserve transplantation
      of donor feces for recurrent and difficult cases of CDI is a possible risk of pathogen
      transmittance and the process of finding a donor and screen for communicable disease.

      The effect of FMT for recurrent CDI, however, suggests that this therapy may be more
      effective than antibiotics in inducing a durable cure also for primary CDI. If the
      therapeutic effect of FMT proves to be equal (non-inferior) or more effective than
      antibiotics, FMT may be the preferable treatment option due to favourable ecological impact
      compared to antibiotics. In an era with increasing concerns about overuse of antibiotics and
      emergence of antibiotic resistant bacteria, it is important to investigate therapeutic
      alternatives that may reduce the need for antibiotics.

      This trial is a phase III multicentre, randomized controlled, open-label non-inferiority
      parallel group trial with two arms (FMT and antibiotics), and is a continuation of the phase
      II trial IMT for Primary Clostridium Difficile Infection (NCT02301000). In the current trial,
      patients with Clostridium difficile infection and no previous CDI within 12 months prior to
      inclusion will be randomized 1:1 to FMT or 10 days of guideline-recommended antibiotic
      therapy (vancomycin 125 mg four times a day).

      Patients are recruited in Norwegian hospitals.

      The investigators plan to use frozen microbiota, because supply is easier to organize,
      compared to fresh fecal samples. Patients in the FMT treatment group will receive one rectal
      dose of FMT, originating from screened, healthy donors. Patients who are not cured by the
      first dose is offered a protocol defined additional FMT treatment. In the case of clinical
      deterioration, appropriate measures will be undertaken according to current guidelines.

      Patient treatment outcomes are evaluated after 14, 60 and 365 days from inclusion and
      treatment initiation.

      An interim analysis is planned after inclusion of the first 94 patients (corresponding to 50%
      of the planned number of patients).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.
primary purpose: Treatment
masking: None (Open Label)
masking description: An open-label, partly assessor blinded trial.
measure: Patients with durable cure
time frame: 60 days
description: Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with the assigned treatment alone.
measure: Patients with durable cure with additional treatment.
time frame: 60 days
description: Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, with or without the need of additional treatment (FMT, metronidazole or vancomycin).
measure: Treatment adverse events
time frame: 60 and 365 days
description: Proportion of patients with adverse events.
measure: Patients with long-time cure
time frame: 365 days
description: Proportion of patients with primary clinical cure at day 14 after treatment start and no recurrent C. difficile infection during 60 days after treatment start, and without recurrent C. difficile infection within 365 days after treatment start.
measure: Health-economic evaluation
time frame: 365 days
description: Health-economic analysis of the two compared treatment modalities
measure: Fecal composition and treatment outcome
time frame: 60 days
description: Correlation in fecal composition changes before versus after treatment, and treatment outcome (such as bacterial diversity and fecal short chain fatty acids).
Subgroup analyses will be performed for sex, age, co-morbidities, and FMT donor.
arm group label: Fecal microbiota transplantation
arm group type: Experimental
description: Fecal microbiota from healthy, screened stool donors at the University Hospital of North Norway. Patients will receive one FMT enema immediately after enrolment.
arm group label: Antibiotic treatment
arm group type: Active Comparator
description: Patients randomized to the control group will receive a ten-day course of oral vancomycin four times a day. This is according to international guidelines for primary C. difficile treatment.
intervention type: Other
intervention name: Fecal microbiota transplantation
description: 50 g donor feces suspended in saline with added glycerol, administered by a enema kit.
arm group label: Fecal microbiota transplantation
other name: FMT
other name: IMT
other name: Bacteriotherapy
intervention type: Drug
intervention name: Vancomycin
description: Peroral vancomycin 125 mg q.i.d. for ten days.
arm group label: Antibiotic treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Bretthauer, MD, PhD
role: Study Chair
affiliation: Oslo Universitetssykehus HF, Rikshospitalet
last name: Kjetil Garborg, MD, PhD
phone: +4741578975
email: k.k.garborg@medisin.uio.no
last name: Frederik Emil Juul, MD
phone: +4797512966
email: f.e.juul@medisin.uio.no
facility: 
status: Recruiting
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status: Not yet recruiting
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country: Norway
url: https://www.med.uio.no/helsam/english/research/groups/clinical-effectiveness/index.html
description: Investigating research group' home page
citation: McDonald LC, Gerding DN, Johnson S, Bakken JS, Carroll KC, Coffin SE, Dubberke ER, Garey KW, Gould CV, Kelly C, Loo V, Shaklee Sammons J, Sandora TJ, Wilcox MH. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018 Mar 19;66(7):987-994. doi: 10.1093/cid/ciy149.
PMID: 29562266
citation: Juul FE, Garborg K, Bretthauer M, Skudal H, Oines MN, Wiig H, Rose O, Seip B, Lamont JT, Midtvedt T, Valeur J, Kalager M, Holme O, Helsingen L, Loberg M, Adami HO. Fecal Microbiota Transplantation for Primary Clostridium difficile Infection. N Engl J Med. 2018 Jun 28;378(26):2535-2536. doi: 10.1056/NEJMc1803103. Epub 2018 Jun 2. No abstract available.
PMID: 29860912
citation: Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015 Apr 16;372(16):1539-48. doi: 10.1056/NEJMra1403772. No abstract available.
PMID: 25875259
citation: van Nood E, Dijkgraaf MG, Keller JJ. Duodenal infusion of feces for recurrent Clostridium difficile. N Engl J Med. 2013 May 30;368(22):2145. doi: 10.1056/NEJMc1303919. No abstract available.
PMID: 23718168
citation: Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013 Apr;108(4):500-8. doi: 10.1038/ajg.2013.59. Epub 2013 Mar 19.
PMID: 23511459
responsible party type: Principal Investigator
investigator affiliation: Oslo University Hospital
investigator full name: Kjetil Garborg
investigator title: Joint Principal Investigator
mesh term: Infections
mesh term: Communicable Diseases
mesh term: Clostridium Infections
mesh term: Vancomycin
sharing ipd: Undecided
ipd description: The trial adheres to data sharing policies of the ICMJE. Data sharing is considered for each request by the principal investigators. Data sharing is not granted if they overlap with planned analyses. Data sharing requires all approvals by relevant authorities. Costs for data sharing will not be covered by the study group.