COLONIZE: Transplantation of intestinal microbiota in primary Clostridioides difficile infections

Objectives

The trial investigates whether the administration of intestinal microbiota from healthy donors (i.e. fecal bacteria and –matter) is equal or more effective than antibiotics in the prevention and treatment of first-time Clostridioides difficile (formerly Clostridium difficile) infections. The goal is to give patients better treatment in terms of both faster recovery and fewer recurrences of the disease.

Background

Clostridioides difficile infections can occur due to dusturbances in the microbial composition in the intestine following antibiotic treatment for another infection. Clostridioides difficile infections varies in severity, from mild diarrhea and abdominal pain, to severe colitis that may be fatal. As the infection typically emerge in persons exposed to antibiotic treatment, it occurs frequently in hospitals and often prolongs hospitalization. The incidence of Clostridioides difficile infections has increased over the last decades.

Standard treatment for Clostridioides difficile infections are antibiotics, but 15-25% of  patients experience persistent symptoms, or rapid relapse of the infection. Transmission of healthy intestinal microbiota (fecal microbiota transplantation) is shown to be more effective than antibiotics as treatment for recurrent Clostridoides difficile infections but, as of today, the patients have to suffer through multiple infections and antibiotic treatments before fecal microbiota transplantation is an option.

Our hypothesis is that the fecal microbiota transplantation treatment instead of, or as adjuvant, to antibiotics is better than antibiotics alone in the treatment of first-time Clostridioides difficile infections and in prevention of disese recurrences.

We hope to show that treatment with intestinal microbiota in first-time Clostridoides difficile infection can help reduce the use of antibiotics and costs associated with hospitalizations due to Clostridoides difficile infections.

Phases

Phase 1 - Microbiota transplantation as treatment in first-time Clostridoides difficile infection. Scientific Title: COLONIZE - COmparative effectiveness of intestinaL microbiOta versus vaNcomycin for primary c. difficile Infection - randomiZEd Trials

The trial started enrolment in 2019 and was completed in 2024. the trial is registered at clinicaltrials.gov

Phase 2 - Safety and cost-effectiveness analysis of fecal microbiota transplantation in primary Clostridoides difficile infections.
 

Cooperation

The Clinical Effectiveness research group in collaboration with hospitals in Norway and scientific expertice in the United States are conducting the trial.

• Oslo University Hospital, Rikshospitalet

• Oslo University Hospital, Ullevål

• University Hospital og North-Norway, Harstad

• University Hospital og North-Norway, Tromsø

• Vestre Viken Bærum Hospital, Bærum
• Vestfold Hospital, Tønsberg

• Telemark Hospital, Skien

• Sørlandet Sykehus Health Trust, Kristiansand

• Haukeland University Hospital, Bergen

• Østfold Hospital, Kalnes

• Ålesund Hospital, Ålesund
• Nordmøre og Romsdal Hospital, Hjelset
• Levanger Hospital, Levanger

• Lovisenberg Diaconale Hospital, Oslo

• Akershus University Hospital

• Nordland Hospital, Bodø

• Diakonhjemmet Hospital, Oslo

• Fürst Medical Lab, Oslo

• Innlandet Hospital Trust, Lillehammer

• Stavanger University Hospital, Stavanger

Timeline

A pilot to the COLONIZE trial was completed in 2018 and the results published in The New England Journal of Medicine. The publication caught media's attention, including the New York Times.

The main trial started summer 2019 and completed patient enrolment in 2024.

References

Mullish, B.H. et al. The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines Journal of Hospital Infection, 2024, Volume 148, 189 - 219.

Baunwall SMD et al. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis. EClinicalMedicine. 2020 Nov 23:29-30:100642. doi: 10.1016/j.eclinm.2020.100642. eCollection 2020 Dec.

Leffler DA, Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015;373(3):287-8.