Fecal Transplantation for Primary Clostridium Difficile Infection

NCT03796650 | Terminated Phase 3 DMC

• 1 other identifier: COLONIZE
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 18

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.

Conditions

Clostridium Difficile Infection

Keywords

Clostridium difficile; Intestinal microbiota therapy; Fecal microbiota transplantation; Investigator-initiated; Antibiotics; Diarrhea

Outcome Measures

Primary Outcomes (1)

• Patients with durable cure

  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.

  60 days

Secondary Outcomes (4)

• Patients with durable cure with additional treatment.

  60 days

• Treatment adverse events

  60 and 365 days

• Patients with long-time cure

  365 days

• Health-economic evaluation

  365 days

Other Outcomes (1)

• Fecal composition and treatment outcome

  60 days

Study Arms (2)

Fecal microbiota transplantation

EXPERIMENTAL

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

Antibiotic treatment

ACTIVE COMPARATOR

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

Interventions

Fecal microbiota transplantation OTHER

50 g donor feces suspended in saline with added glycerol, administered by a enema kit.

Also known as: FMT, IMT, Bacteriotherapy

Fecal microbiota transplantation

Vancomycin DRUG

Peroral vancomycin 125 mg q.i.d. for ten days.

Antibiotic treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, ≥18 years with primary C. difficile infection, defined by the following three criteria:
• Diarrhea as defined by the WHO (≥3 loose stools per day), and
• Positive stool test for toxin producing C. difficile, and
• No evidence of previous C. difficile infection during 365 days before enrolment.
• Written informed consent

You may not qualify if:

• Known presence of other stool pathogens known to cause diarrhea.
• Ongoing antibiotic treatment for other infections that cannot be stopped before study treatment administration.
• Inflammatory bowel disease or microscopic colitis.
• \< 3 months life expectancy.
• Serious immunodeficiency, defined as one of the following:
• Ongoing or recent chemotherapy and current or expected neutropenia with neutrophil count of \< 500/μL.
• Active severe immunocompromising disease.
• Inability to comply with protocol requirements.
• Need of intensive care.
• Known irritable bowel syndrome, diarrheal type.
• Pregnancy or nursing.
• Known or suspected toxic megacolon or ileus.
• Total or subtotal colectomy, ileostomy or colonostomy.
• Contraindications for rectal catheter insertion
• Known hypersensitivity or other contraindications to vancomycin

Sponsors & Collaborators

• Oslo University Hospital: lead
• South-Eastern Norway Regional Health Authority: collaborator
• University Hospital of North Norway: collaborator
• Haukeland University Hospital: collaborator
• Helse Nord-Trøndelag HF: collaborator
• Vestre Viken Hospital Trust: collaborator
• The Hospital of Vestfold: collaborator
• Sykehuset Telemark: collaborator
• Alesund Hospital: collaborator
• University Hospital, Akershus: collaborator
• Lovisenberg Diakonale Hospital: collaborator
• Sorlandet Hospital HF: collaborator
• Ostfold Hospital Trust: collaborator
• Diakonhjemmet Hospital: collaborator
• Nordlandssykehuset HF: collaborator
• Sykehuset Innlandet HF: collaborator
• Helse Stavanger HF: collaborator

Study Sites (18)

Vestre Viken HF, Bærum Hospital

Sandvika, Gjettum, 1346, Norway

Location

Diakonhjemmet Hospital

Oslo, Oslo County, 0319, Norway

Location

Ålesund Sjukehus

Ålesund, Norway

Location

Haukeland universitetssykehus

Bergen, Norway

Location

Nordlandssykehuset

Bodø, 8092, Norway

Location

Sykehuset Østfold Kalnes

Grålum, Norway

Location

UNN Harstad

Harstad, Norway

Location

Sørlandet Hospital HF

Kristiansand, Norway

Location

Sykehuset Levanger

Levanger, Norway

Location

Sykehuset Innlandet HF

Lillehammer, Norway

Location

Akershus University Hospital

Lørenskog, 1478, Norway

Location

Lovisenberg sykehus

Oslo, Norway

Location

Oslo University Hospital Rikshospitalet

Oslo, Norway

Location

Oslo University Hospital Ullevål

Oslo, Norway

Location

Telemark Hospital HF

Skien, Norway

Location

Stavanger University Hospital

Stavanger, Norway

Location

UNN Tromsø

Tromsø, Norway

Location

Sykehuset i Vestfold

Tønsberg, Norway

Location

Related Publications (6)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Juul FE, Bretthauer M, Johnsen PH, Samy F, Tonby K, Berdal JE, Hoff DAL, Ofstad EH, Abraham A, Seip B, Wiig H, Rognstad OB, Glad IF, Valeur J, Nissen-Lie AE, Ness-Jensen E, Lund KMA, Skjevling LK, Hanevik K, Skudal H, Melsom EJ, Boyar R, Cooper TJ, Ranheim TE, Riise EM, Adami HO, Kalager M, Loberg M, Garborg KK. Fecal Microbiota Transplantation Versus Vancomycin for Primary Clostridioides difficile Infection : A Randomized Controlled Trial. Ann Intern Med. 2025 Jul;178(7):940-947. doi: 10.7326/ANNALS-24-03285. Epub 2025 Jun 17.

  PMID: 40523286 DERIVED

Related Links

• Investigating research group' home page

MeSH Terms

Conditions

Clostridium Infections; Diarrhea

Interventions

Fecal Microbiota Transplantation; Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Michael Bretthauer, MD, PhD

  Oslo Universitetssykehus HF, Rikshospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: An open-label, partly assessor blinded trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Joint Principal Investigator

Model Details: Randomized clinical trial with two parallel treatment arms with a 1:1 allocation.

Study Record Dates

• First Submitted: January 4, 2019
• First Posted: January 8, 2019
• Study Start: July 17, 2019
• Primary Completion: April 2, 2024
• Study Completion: April 2, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Locations

NO (18)