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Fecal Transplantation for Primary Clostridium Difficile Infection (COLONIZE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03796650
Recruitment Status : Recruiting
First Posted : January 8, 2019
Last Update Posted : July 18, 2019
Frontier Science & Technology Research Foundation, Inc.
South-Eastern Norway Regional Health Authority
University Hospital of North Norway
Haukeland University Hospital
Levanger Hospital
Information provided by (Responsible Party):
Kjetil Garborg, Oslo University Hospital

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Clostridium Difficile Infection Other: Fecal microbiota transplantation Drug: Vancomycin Phase 3

Detailed Description:

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 188 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.
Masking: None (Open Label)
Masking Description: An open-label, partly assessor blinded trial.
Primary Purpose: Treatment
Official Title: COmparative Effectiveness of intestinaL microbiOta Versus vaNcomycin for Primary c. Difficile Infection - randomiZEd Trials
Actual Study Start Date : July 17, 2019
Estimated Primary Completion Date : January 31, 2024
Estimated Study Completion Date : January 31, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bowel Movement

Arm Intervention/treatment
Experimental: Fecal microbiota transplantation
Fecal microbiota from healthy, screened stool donors at the University Hospital of North Norway. Patients will receive one FMT enema immediately after enrolment.
Other: Fecal microbiota transplantation
50 g donor feces suspended in saline with added glycerol, administered by a enema kit.
Other Names:
  • FMT
  • IMT
  • Bacteriotherapy

Active Comparator: Antibiotic treatment
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.
Drug: Vancomycin
Peroral vancomycin 125 mg q.i.d. for ten days.

Primary Outcome Measures :
  1. Patients with durable cure [ Time Frame: 60 days ]
    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.

Secondary Outcome Measures :
  1. Patients with durable cure with additional treatment. [ Time Frame: 60 days ]
    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).

  2. Treatment adverse events [ Time Frame: 60 and 365 days ]
    Proportion of patients with adverse events.

  3. Patients with long-time cure [ Time Frame: 365 days ]
    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.

  4. Health-economic evaluation [ Time Frame: 365 days ]
    Health-economic analysis of the two compared treatment modalities

Other Outcome Measures:
  1. Fecal composition and treatment outcome [ Time Frame: 60 days ]

    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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients, ≥18 years with primary C. difficile infection, defined by the following three criteria:

    1. Diarrhea as defined by the WHO (≥3 loose stools per day), and
    2. Positive stool test for toxin producing C. difficile, and
    3. No evidence of previous C. difficile infection during 365 days before enrolment.
  • Written informed consent

Exclusion Criteria:

  • No known presence of other stool pathogens known to cause diarrhea.
  • No ongoing or scheduled (e.g. surgery prophylaxis) antibiotic treatment for other infections that cannot be stopped for 12 hours after treatment allocation.
  • No inflammatory bowel disease or microscopic colitis.
  • >3 months life expectancy.
  • No serious immunodeficiency, defined as one of the following two criteria: (A) Ongoing or recent chemotherapy and current or expected neutropenia with neutrophil count of <500/µL. (B) Active severe immunocompromising disease.
  • Ability to comply with protocol requirements.
  • No need of intensive care or American Society of Anesthesiologists (ASA) Physical Status classification IV or V.
  • No known irritable bowel syndrome, diarrheal type.
  • No pregnancy or nursing.
  • No known or suspected toxic megacolon or ileus.
  • No total or subtotal colectomy, ileostomy or colostomy.
  • No known hypersensitivity or other contraindications to vancomycin.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03796650

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Contact: Kjetil Garborg, MD, PhD +4741578975
Contact: Frederik Emil Juul, MD +4797512966

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Vestre Viken HF, Bærum Hospital Not yet recruiting
Sandvika, Gjettum, Norway, 1346
Contact: Øystein Rose, MD         
Haukeland universitetssykehus Not yet recruiting
Bergen, Norway
Contact: Trygve Hausken, MD, PhD         
Sykehuset Østfold Kalnes Not yet recruiting
Grålum, Norway
Contact: Jon Birger Haug, MD, PhD         
UNN Harstad Not yet recruiting
Harstad, Norway
Contact: Peter H. Johnsen, MD         
Sørlandet Hospital HF Not yet recruiting
Kristiansand, Norway
Contact: Håvard Wiig, MD         
Sub-Investigator: Rita Helleren, MD         
Sykehuset Levanger Not yet recruiting
Levanger, Norway
Contact: Eivind Ness-Jensen, MD, PhD         
Lovisenberg sykehus Not yet recruiting
Oslo, Norway
Contact: Jørgen Valeur, MD         
Oslo University Hospital Rikshospitalet Recruiting
Oslo, Norway
Contact: Frederik Emil Juul, MD   
Contact: Siv Elisabeth Isaksen         
Principal Investigator: Kjetil Garborg, MD, PhD         
Oslo University Hospital Ullevål Recruiting
Oslo, Norway
Contact: Kristian Tonby, MD, PhD         
Sub-Investigator: Frederik Emil Juul, MD         
Telemark Hospital HF Not yet recruiting
Skien, Norway
Contact: Hilde Skudal, MD         
UNN Tromsø Not yet recruiting
Tromsø, Norway
Contact: Rasmus Goll, MD         
Sykehuset i Vestfold Not yet recruiting
Tønsberg, Norway
Contact: Birgitte Seip, MD         
Ålesund Sjukehus Not yet recruiting
Ålesund, Norway
Contact: Dag Arne Lihaug Hoff, MD         
Sponsors and Collaborators
Oslo University Hospital
Frontier Science & Technology Research Foundation, Inc.
South-Eastern Norway Regional Health Authority
University Hospital of North Norway
Haukeland University Hospital
Levanger Hospital
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Study Chair: Michael Bretthauer, MD, PhD Oslo Universitetssykehus HF, Rikshospitalet

Additional Information:
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Responsible Party: Kjetil Garborg, Joint Principal Investigator, Oslo University Hospital Identifier: NCT03796650     History of Changes
Other Study ID Numbers: COLONIZE
First Posted: January 8, 2019    Key Record Dates
Last Update Posted: July 18, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan 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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Kjetil Garborg, Oslo University Hospital:
Clostridium difficile
Intestinal microbiota therapy
Fecal microbiota transplantation

Additional relevant MeSH terms:
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Communicable Diseases
Clostridium Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Anti-Bacterial Agents
Anti-Infective Agents