Clostridioides difficile infection (CDI) is the most frequent cause of infectious
diarrhea in hospitalized patients and is responsible for 20-30 % of antibiotic-associated
diarrhea cases. Inflammatory bowel diseases (IBD) are associated with an higher
prevalence, recurrence and severity of CDI. The prevalence of recurrent CDI in patients
with IBD is 2.5 to 8 times higher than in the general population, with a cumulative
lifetime risk of 10 %. The higher risk to the development of CDI in patient with IBD is
directly related to the microbiome alterations that are associated with this chronic
disoder. Moreover, the use of antibiotics to cure CDI further worsens the gut microbiota,
triggering potentially a self-maintaining cycle and predisposes such patients to a higher
risk of recurrence. In these patients, CD superinfection is associated, with an increased
rate of hospitalization, length of stay, the need to modify the treatment to the
underlying disease, the increase rate of colectomy, there higher mortality rate, with a
net increase of health costs.
Nowadays, as emerged by several studies FMT has been established as a valid treatment
option against recurrent CDI (rCDI), and it is recommended by international guidelines.
Unfortunately, most FMT studies for rCDI have excluded patients with IBD. Recent evidence
suggests that FMT is effective in patients with ulcerative colitis (UC) and concomitant
rCDI, both in the treatment of the infection and in the improve of disease activity. To
date, most studies evaluated the efficacy of single infusion of FMT in these patients.
Preliminary data from our group suggest that a sequential approach (i.e., repeated fecal
infusions) may increase the efficacy of FMT in this population. Indeed, in 18 patients
with IBD, single infusion fecal resulted in eradication of rCDI in 60% of cases, whereas
this outcome was achieved in 89% of cases using a sequential approach. Similar data have
been demonstrated in a retrospective study by Fischer and colleagues. However, more
studies are advocated to confirm these results.
Therefore, our study aim to compare the efficacy of single FMT vs. sequential in the
eradication of rCDI in patients with UC.
The extended aims of our study are:
To compare the efficacy of single FMT versus sequential FMT in eradicating rCDI in
patients with UC at 8 weeks after the end of treatment.
To compare the efficacy of single FMT versus sequential FMT in the eradication of
rCDI in patients with UC in the short term (1-4 weeks after the end of treatment).
To evaluate the safety of the two treatments.
To evaluate any changes in the microbiota following treatment.
To assess disease activity of UC by clinical scores (partial Mayo score) at 8 weeks.
The investigators will carry out a randomized, controlled, open-label, single-clinical
trial of single FMT vs sequential FMT in patients with active UC with concomitant rCDI,
will be recruited among those referred to the gastroenterology unit of the Fondazione
Policlinico Universitario "A. Gemelli". Patients with all inclusion criteria and none of
the exclusion criteria (detailed in the specific section of this website) will be
considered for this study.
Before randomization, demographic data will be collected by the gastroenterology staff.
Moreover, patients will be requested to give stool samples to be collected in a sterile,
sealed container and stored at -80°C for metagenomic assessment of gut microbiome by the
microbiology staff.
After baseline assessments, patients will be randomly assigned to one of the following
treatment arms:
Single FMT (Si-FMT);
Sequential FMT (Se-FMT), consisting of 3 fecal infusions, each 3-6 days apart,
within 18 days after randomization.
Each patient will undergo FMT procedure through colonoscopy under sedation; Fecal
infusates will be delivered through the operative of the colonoscope, using 50-mL
syringes.
Patients in the Si-FMT and Se-FMT arms will receive frozen feces from a healthy non
related donor following the protocols suggested by the international guidelines. Patients
in the Se-FMT arm will receive frozen feces from the same donor.
The selection of stool donors will be performed by the gastroenterology staff following
protocols previously recommended by international guidelines and according the new
recommendation imposed by the reorganization of fecal microbiota transplant during the
COVID-19 pandemic.
The assignment of fecal infusates from healthy donors to patients will be done randomly,
without any specific recipient- donor match, as this is not recommended by international
guidelines All fecal infusates will be manufactured in the microbiology unit of our
hospital. Only frozen feces will be used. Preparation of frozen feces will follow
protocols from international guidelines.
Follow-up visits will be performed by physicians from the gastroenterology unit. All
patients will be followed up for 2 months after the end of treatments. Follow- up visits
will be scheduled at week 1, week 4, and week 8, after the end of treatments.
At each visit the following assessments will be performed: 1) collection of a stool
sample for C. difficile toxin evaluation; 2) collection of a stool sample for metagenomic
analysis of the gut microbiota; 3) clinical evaluation of disease activity; and 4)
recording of adverse events.
Study Outcomes are detailed in the specific section of this website.
The statistical analysis will be performed both on an intention-to-treat and per-
protocol basis. Differences among groups will be assessed with a two tailed Wilcoxon-rank
sum test for continuous data and with Fisher's exact probability test (using two-tailed
P-values) for categorical data. Differences in cure percentages will be determined with
Fisher's exact test (with two-tailed P values). Microbiome analysis will be performed
with shotgun sequencing techniques. For microbiome analysis statistical differences
between group means will be calculated using a two-tailed Wilcoxon-Rank Sum Test, through
the R statistical software package (R Core Team, Vienna, Austria).
