COLONIZE: Transplantation of intestinal microbiota in primary Clostridoides difficile infections

Objectives

We are investigating whether the supply of intestinal microbiota (i.e. fecal bacteria and –matter) is more effective than antibiotics in the prevention and treatment of first-time Clostridoides 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

Clostridoides difficile infections can occur due to disturbed intestinal microbial organisms after antibiotic treatment for another infection. Clostridoides difficileinfections 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 Clostridoides difficile infections has increased over the last decades.

Standard treatment for Clostridoides difficile infections are antibiotics, but around one in four patients experience persistent symptoms, or rapid relapse of the infection. Transmission of healthy intestinal microbiota 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 intestinal microbiota is an option.

Our hypothesis is that the supply of intestinal microbiota instead, or as adjuvant, to antibiotics is better than antibiotics alone in the treatment of first-time Clostridoides difficile infections and in prevention of recurrent Clostridoides difficile infections. We investigate this in two different trials. The pilot of the first trial was completed at the beginning of 2018 and the other will be launched soon.

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.

Trials

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 study is registered in clinicaltrials.gov

2 - Microbiota transplantation to prevent relapse of Clostridoides difficile infection.
Scientific Title: RCT of Microbiota Therapy to Prevent Recurrence of Clostridoides difficile Infection after Antibiotic Treatment

Cooperation

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

• Oslo University Hospital, Rikshospitalet

• Oslo University Hospital, Ullevål

• University Hospital og North-Norway, Harstad

• University Hospital og North-Norway, Tromsø

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

• Telemark Hospital, Skien

• Sørlandet Sykehus Health Trust, Kristiansand

• Haukeland University Hospital, Bergen

• Østfold Hospital, Kalnes

• Ålesund Hospital, Ålesund
• 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 trials 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 is expected to end in 2024.

References

Vincent C, Stephens DA, Loo VG, Edens TJ, Behr MA, Dewar K, et al. Reductions in intestinal Clostridiales precede the development of nosocomial Clostridium difficile infection. Microbiome. 2013;1(1):18.

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

Dubberke ER, Olsen MA. Burden of Clostridium difficile on the healthcare system. Clin Infect Dis. 2012;55.

Khanna S, Pardi DS. The growing incidence and severity of Clostridium difficile infection in inpatient and outpatient settings. Expert Rev Gastroenterol Hepatol. 2010;4.

Barbut F, Richard A, Hamadi K, Chomette V, Burghoffer B, Petit JC. Epidemiology of recurrences or reinfections of Clostridium difficile-associated diarrhea. J Clin Microbiol. 2000;38(6):2386-8.

Kassam Z, Lee CH, Yuan Y, Hunt RH. Fecal microbiota transplantation for Clostridium difficile infection: systematic review and meta-analysis. Am J Gastroenterol. 2013;108(4):500-8.

Senior K. Faecal transplantation for recurrent C difficile diarrhoea. Lancet Infect Dis. 2013;13.