Clinical trial NCT03479710: Fecal Microbiota Transplantation for CRE/VRE
Official title: Fecal Microbiota Transplantation for Eradication of Intestinal Colonization of Carbapenem-resistant Enterobacteriaceae and Vancomycin-resistant Enterococcus: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Antimicrobial Resistance
Colonization
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2018-03-27
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multidrug-resistant organisms (MDRO) present an increasingly serious public health threat to the global community.The prevalence of various MDRO, including carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant Enterococcus (VRE), has been increasing worldwide, and some have become endemic in certain countries. Data from the Hospital Authority showed that the number of carbapenemase- producing Enterobacteriaceae (CPE) cases increased from 36 in 2012 to 134 in 2015. A large outbreak of VRE involving \>200 patients was recently reported in a tertiary hospital in Hong Kong.

The primary site of colonization and persistence of most MDRO is in the gastrointestinal tract. Carriage can persist for months, with up to 40% of individuals still having colonization one year after hospital discharge. Outbreaks of MDRO have been reported in hospitals and long-term care facilities. Around 10% of patients colonized with MDRO would develop clinical infections by the same organism. Infections caused by these MDRO carry significant morbidity and high mortality of up to 50%, however, there is no proven therapy for eradication of intestinal colonization of MDRO.

There is accumulating evidence showing that the gut microbiota plays an important role in the control of intestinal colonization and infection by pathogenic bacteria. Administration of obligate anaerobic commensal bacteria to mice has been shown to markedly reduce VRE colonization. Preliminary evidence, mainly from anecdotal reports, have shown that fecal microbiota transplantation (FMT) in human carriers of MDRO were safe and potentially effective in eliminating intestinal colonization by various MDRO, including CRE and VRE, even in immunocompromised patients. Therefore, investigators hypothesize that FMT will be safe and potentially effective in eradicating intestinal colonization of CRE and VRE.

This is a prospective pilot study to evaluate whether FMT is safe and effective to eradicate intestinal colonization of CRE and VRE.


Eligibility criteria: Inclusion Criteria:

For cases:

1. Age ≥18 years old
2. Two or more stool or rectal swab positive for CRE or VRE at least one week apart.

   \[CRE is defined as presence of any Enterobacteriaceae with resistance to any of the carbapenems. VRE is defined as presence of Enterococcus species resistant to vancomycin.\]
3. Not receiving antimicrobial therapy for at least 48 hours prior to infusion of FMT

For controls:

1. Age ≥18 years old
2. Two or more stool or rectal swab positive for CRE or VRE at least one week apart.
3. Not receiving antimicrobial therapy for at least 48 hours prior to infusion of FMT
4. Refuse to consent for FMT infusion but consent for other study procedures listed in the protocol.

Exclusion Criteria:

1. Active infection with CRE or VRE requiring antimicrobial therapy
2. Pregnancy
3. Active gastrointestinal tract infection or inflammatory disorders
4. Recent intra-abdominal surgery
5. Short gut syndrome
6. Use of medications which alter gastrointestinal motility at the time of inclusion
7. Post-allogeneic hematopoietic stem cell transplant patients with history of gastrointestinal tract graft versus host disease
8. Presence of intra-abdominal device which would increase risk of peritonitis
9. ANC \<500/mm3
10. HIV infection with CD4 \<200 cells/mm3
11. On chemotherapy

Primary outcomes:
measure: Intestinal colonization of CRE/VRE
timeFrame: 2 weeks to 12 months
Secondary outcomes:
measure: Adverse events
timeFrame: 12 months post FMT
measure: Intestinal microbiota
timeFrame: Before and 12 months after FMT
Other outcomes:
Locations:
city: Sha Tin
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: CUHK
name: Grace Lui
role: PRINCIPAL_INVESTIGATOR
References: