LyophilizeD fecal micrObiome traNsfer for primAry closTridioides difficilE infection (DONATE study): a multicenter randomized controlled trial
( DONATE )
Primary Clostridioides difficile infection (pCDI) carries high recurrence and mortality rates and is globally spread. pCDI is often a consequence of exposure to antibiotics, disrupting the healthy intestinal microbiota composition. Not surprisingly, in this antibiotic-associated infection, failure of the standard antibiotic treatment is high. Frozen fecal microbiota transplantation (FMT), the introduction of the microbial community from a healthy donor, has been shown to be safe and highly effective in cases of recurrent CDI, reaching >90% cumulative success rate. Importantly, FMT has shown potential for eradication of other multidrug resistant organisms (MDRO) carriage. The use of FMT for pCDI, has been tested in small studies, showing promising results. The use of frozen FMT is hampered by storage needs which limit accessibility and spread. We have developed a lyophilized FMT product (Lyo-FMT - a dry compound that does not need freezing) that retains viability, prolongs the shelf time of the product and improves patient acceptance. In a randomized controlled multicenter trial, we aim to assess the efficacy of Lyo-FMT for pCDI in comparison to standard antibiotic therapy. This easy-to-administer product will restore the microbial community, fight the infective agent and reduce the overall antibiotic-resistant gene burden. This, in turn, will lower the recurrence rate and decrease carriage of other MDRO, coupled with a reduction in antibiotic use. Data on microbial shifts during treatment will shed light on our understanding of the pathophysiology of the disease.
- Milena Pitashny, Rambam Health Care Campus, Israel (Coordinator)
- Nicola Segata, European Institute of Oncology, Italy (Partner)
- Dina Kao, University of Alberta, Canada (Partner)
- Bejamin Mullish, Imperial College London, United Kingdom (Partner)
- Gergely Nagy, University of Debrecen, Hungary (Partner)
- Juozas Kupcinskas, Lithuanian University of Health Sciences, Lithuania (Partner)
- Gianluca Ianiro, IRCCS Fondazione Policlinico Universitario A. Gemelli, Italy (Partner)
Primary Clostridioides difficile infection (pCDI) is a gastrointestinal infection that presents with diarrhea, fever and abdominal pain and is often resistant to antibiotic therapy. pCDI is often a consequence of previous exposure to antibiotics that disrupt the balance of healthy microbes that reside in our gut. Fecal microbiota transplantation (FMT), the introduction of a healthy microbial community from a healthy donor, has been shown to be safe and highly effective in patients who experience recurrence of CDI, but was not vigorously tested in primary infection. FMT can also fight other deleterious microbes that might reside in the gut. Since FMT contains live bacteria, it needs to be kept frozen until administration. We have developed a dry compound that does not need freezing (Lyo-FMT) and aim to assess its efficacy for pCDI. This easy-to-administer product will restore the healthy bacterial community, fight infection and reduce the use of antibiotics. If effective, this study will revolutionize the treatment of this worldwide distributed infection.