Clinical trial NCT02570477: FMT for Moderate to Severe CDI: A Randomised Study With Concurrent Stool Microbiota Assessment
Official title: Fecal Microbiota Transplantation (FMT) for Moderate to Severe Clostridium Difficile Infection (CDI): A Randomised Study With Concurrent Stool Microbiota Assessment (FMT-CDI-RCT Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Clostridium Difficile Infection
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2015-10-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness, associated with significant morbidity and mortality and has a high burden on health-care system. The incidence of CDI has increased to epidemic proportion worldwide over the past decade. Community-acquired CDI, elderly and hospitalized patients receiving antibiotics are the main group at risk for developing CDI.

Currently, the first-line treatment for C. difficile-associated diarrhea includes cessation of the antibiotic implicated in the development of CDI, treatment with metronidazole or vancomycin and recently Fidaxomicin which is yet to be available in Hong Kong. However, disease recurrence is an increasing problem and 20% to 60% of patients experience at least one recurrence within a few weeks of completion of antibiotic treatment. Moreover, an increasing number of patients who require life-saving emergency colectomy experience persistent CDI after surgery. Until recently, an effective treatment against recurrent CDI is not available. Generally, repeated and extended courses of vancomycin are prescribed.

Fecal microbiota transplantation (FMT) defined as infusion of feces from healthy donors to affected subjects has attracted great interest in recent years and is now recommended as the most effective therapy for CDI not responding to standard therapies. Systematic reviews of prospective trials, case series and one randomized controlled trial have shown an overall cure rate of close to 100%. More than 50% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur.

This proposal aims to investigate the efficacy of FMT as first line therapy in patients with severe CDI and to assess changes in the fecal microbiota after FMT using pyrosequencing techniques.

Detailed description: Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness, associated with significant morbidity and mortality and has a high burden on health-care system. The incidence of CDI has increased to epidemic proportion worldwide over the past decade. Community-acquired CDI, elderly and hospitalized patients receiving antibiotics are the main group at risk for developing CDI 1.

Currently, the first-line treatment for C. difficile-associated diarrhea includes cessation of the antibiotic implicated in the development of CDI, treatment with metronidazole or vancomycin and recently Fidaxomicin which is yet to be available in Hong Kong2. However, disease recurrence is an increasing problem and 20% to 60% of patients experience at least one recurrence within a few weeks of completion of antibiotic treatment. Moreover, an increasing number of patients who require life-saving emergency colectomy experience persistent CDI after surgery. Until recently, an effective treatment against recurrent CDI is not available. Generally, repeated and extended courses of vancomycin are prescribed3.

Fecal microbiota transplantation (FMT) defined as infusion of feces from healthy donors to affected subjects has attracted great interest in recent years and is now recommended as the most effective therapy for CDI not responding to standard therapies 4. Systematic reviews of prospective trials, case series and one randomized controlled trial have shown an overall cure rate of close to 100% 5, 6. More than 50% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur 7.

While FMT has been proven to be effective in refractory CDI, the role of FMT as first-line therapy in a subset of patients with severe CDI, or high risk features for severe CDI has not been studied. These are generally patients in whom the risk of colectomy and mortality is exceedingly high. In addition, the mechanism of FMT in CDI is not completely clear, and limited data are available on the effects of FMT on the microbiota post FMT. It has been suggested that CDI results in deficiencies in fecal flora composition, particularly of Bacteroides and Firmicutes, and these deficiencies in the microbiota facilitate colonization with C. difficile. Microarray analysis in small number of subjects has shown a major shift in the patients' microbiota after donor-feces infusion toward that of the donors8. The experimental tools required for in depth analysis of the intestinal microbiota are now becoming available. This study aims to investigate the efficacy of FMT as first line therapy in patients with moderate to severe CDI and to assess changes in the fecal microbiota after FMT using pyrosequencing techniques.

Eligibility criteria: Inclusion Criteria:

1. C. difficile infection defined as diarrhea (≥3 soft, loose or watery stools per day for at least 2 consecutive days or ≥8 soft or loose stools in 48 hours) and a positive stool test for C. difficile toxin; and
2. Age ≥ 18; and
3. Written informed consent obtained

Exclusion Criteria:

1. The presence of human immunodeficiency virus (HIV) infection with a CD4 count of less than 240
2. Pregnancy
3. GI Bleeding
4. Acute coronary syndrome

Primary outcomes:
measure: Number of participants cured without relapse within 10 weeks after the initiation of therapy
timeFrame: 10 weeks
Secondary outcomes:
measure: 30-day mortality rate
timeFrame: 30 days
measure: 30-day colectomy rates
timeFrame: 30 days
measure: Number of day of hospital stay
timeFrame: up to 30 days
measure: Changes in the stool microbiota after FMT measured using pyrosequencing
timeFrame: 30 days
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
Study officials:
affiliation: Chinese University of Hong Kong
name: Siew Chien Ng
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zuo T, Wong SH, Lam K, Lui R, Cheung K, Tang W, Ching JYL, Chan PKS, Chan MCW, Wu JCY, Chan FKL, Yu J, Sung JJY, Ng SC. Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome. Gut. 2018 Apr;67(4):634-643. doi: 10.1136/gutjnl-2017-313952. Epub 2017 May 24.