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FMT for Moderate to Severe CDI: A Randomised Study With Concurrent Stool Microbiota Assessment

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Chinese University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
Siew Chien NG, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT02570477
First received: October 5, 2015
Last updated: October 6, 2015
Last verified: October 2015
  Purpose

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.


Condition Intervention
Clostridium Difficile Infection
Procedure: Fecal Microbiota Transplantation
Drug: Vancomycin

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Number of participants cured without relapse within 10 weeks after the initiation of therapy [ Time Frame: 10 weeks ]

Secondary Outcome Measures:
  • 30-day mortality rate [ Time Frame: 30 days ]
  • 30-day colectomy rates [ Time Frame: 30 days ]
  • Number of day of hospital stay [ Time Frame: up to 30 days ]
  • Changes in the stool microbiota after FMT measured using pyrosequencing [ Time Frame: 30 days ]

Estimated Enrollment: 30
Study Start Date: September 2014
Estimated Study Completion Date: August 2016
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: FMT
Fecal Microbiota Transplantation of stool from healthy donor to recipient.
Procedure: Fecal Microbiota Transplantation
Healthy donor is screened and donates feces. It will then be diluted with sterile saline, blended and filtered. Supernatant will be infused to recipient.
Active Comparator: Standard Therapy
125mg Vancomycin four times per day
Drug: Vancomycin
125mg Vancomycin four times per day

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02570477

Contacts
Contact: Siew Chien Ng 852-26321519 siewchienng@cuhk.edu.hk

Locations
China, Hong Kong
Prince of Wales Hospital Recruiting
Hong Kong, Hong Kong, China
Contact: Siew Ng    (852)26321519    siewchienng@cuhk.edu.hk   
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Siew Chien Ng Chinese University of Hong Kong
  More Information

Responsible Party: Siew Chien NG, Associate Professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT02570477     History of Changes
Other Study ID Numbers: FMT-CDI-RCT
Study First Received: October 5, 2015
Last Updated: October 6, 2015

Additional relevant MeSH terms:
Infection
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on March 29, 2017