A Prospective Trial of Frozen-and-Thawed Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection
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|ClinicalTrials.gov Identifier: NCT02394275|
Recruitment Status : Terminated (Principal Investigator has relocated.)
First Posted : March 20, 2015
Last Update Posted : August 15, 2019
|Condition or disease||Intervention/treatment||Phase|
|Clostridium Difficile||Biological: Fecal Microbiota Transplant||Phase 2|
CDI is the most frequent cause of healthcare-associated infectious diarrhea in industrialized countries and affects over 300,000 patients each year in the United States. The incidence of CDI has nearly tripled between 1996 and 2005 (from 31 to 84 per 100,000 patient-days) in the United States. The rise in incidence has been accompanied by an increase in disease severity, with mortality in up to 6.9% of cases. According to the Canadian Nosocomial Infection Surveillance Program study conducted from November 1, 2004 through April 30, 2005, the incidence rate of health care-associated CDI for adult patients admitted to Canadian hospitals is 65 per 100,000 patient-days. The same study identified that the overall and attributable mortality of patients with CDI is 16.3% and 5.7%, respectively in Canada, which is similar to the US data.1,17 The associated economic burden has also been significant. Nosocomial CDI increases the cost of otherwise matched hospitalizations by four-fold, translating to greater than $1 billion/year (United States). Since the implementation of mandatory reporting of CDI cases in September 2008 in Ontario, more than 13 health-care facilities declared CDI outbreak in Ontario. There were a number of deaths directly due to CDI in these outbreaks. The management of each outbreak is very costly. The direct attributable costs associated with the outbreak management alone per episode per institution exceeded $1 million (direct communication with a hospital chief financial officer).
There is a growing concern regarding failure of standard antimicrobial therapy. The treatment failure rates for metronidazole, which is the ﬁrst line therapy for uncomplicated CDI, have risen from 2.5% to greater than 18% since 2000. Recurrence rates are higher among the elderly, and exceed 50% for those over the age 65.20 Recurrence rates exceed 60% for patients who have failed 3 or more episodes of standard antimicrobial therapies. The vanB gene, which is responsible for conferring vancomycin resistance in Enterococcus has been isolated in clostridia, potentially threatening the future use of vancomycin in CDI.
Given the high failure and recurrence rates using the standard therapy, the principal investigator (PI) of this research proposal has been offering FMT for patients who experienced CDI for longer than 6 months despite multiple courses of metronidazole and oral vancomycin therapy. She began treating patients with recurrent CDI with FMT for the following reasons. First, the patients were not responding to the antibiotic treatment. Second, patients may experience intolerance to metronidazole due to metallic taste, significant nausea and loss of appetite, which can lead to further weight loss as patients with CDI experience considerable weight loss. Also, some patients develop irreversible peripheral neuropathy (nerve damage) with long term use of metronidazole. Third, some of the patients with refractory CDI could not afford to continue with oral vancomycin. The cost of oral vancomycin was prohibitive and they were not routinely reimbursed by the public health plan. A 14-day course of oral vancomycin costs $600 and a number of the patients were on this antibiotic for 6 - 18 months at a cost of $7,200 to $21,600 (personal communication with St. Joseph's Healthcare Outpatient pharmacist). The cost of one FMT is approximately $100, which includes the laboratory screening test and the nurse's administration time.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||300 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Prospective Open-Labelled Multi-Centre Trial of Frozen-and-Thawed Fecal Microbiota Transplantation for Recurrent Clostridium Difficile Infection|
|Study Start Date :||March 2014|
|Actual Primary Completion Date :||October 1, 2015|
|Actual Study Completion Date :||August 2019|
Experimental: Single arm:
Eligible patients with receive intervention: frozen fecal microbiota transplantation (FMT), kept at -20 oC and will be thawed prior to administration. Patients on antibiotic to control CDI will discontinue antibiotic 24 hours prior to FMT.
Biological: Fecal Microbiota Transplant
All eligible patients will receive fecal microbiota transplant
Other Name: Human Biotherapy
- cure rate of CDI following FMT [ Time Frame: 13 weeks ]
- safety of FMT as measured by any significant adverse events, including serious adverse events (SAE) [ Time Frame: 13 weeks ]determining any significant adverse events, including serious adverse events (SAE) For each significant event, causality to FMT will be determined by investigators and the DSMB
- Mortality rate directly attributable to CDI [ Time Frame: week 13 ]
- Long-term safety of FMT as measured by questionnaire [ Time Frame: 10 years ]Annual follow-up
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02394275
|Canada, British Columbia|
|Vancouver General Hospital|
|Vancouver, British Columbia, Canada|
|St. Joseph's Healthcare Hamilton|
|Hamilton, Ontario, Canada, L8N 4A6|
|Kingston General Hospital|
|Kingston, Ontario, Canada|