Two-arm, Interventional, Prospective, Open-label, Multi-center Trial to Evaluate the Safety & Effectiveness of FMT for Treatment of Adult Patients With Primary or Recurrent CDI, Using a Novel, Standardized Microbiota Transplantation System
Overview
- Phase
- Not Applicable
- Intervention
- faecal human microbiota transplant (FMT)
- Conditions
- Clostridium Difficile Infection
- Sponsor
- Sejtterapia Kozpont Kft.
- Enrollment
- 150
- Locations
- 3
- Primary Endpoint
- Global cure rate at 10 weeks
- Last Updated
- 9 years ago
Overview
Brief Summary
This study is a two-arm, interventional, prospective, open-label, multi-center clinical trial with randomized and non-randomized study groups to evaluate the safety and effectiveness of faecal microbiota transplantation (FMT) for the treatment of adult patients suffering from primary or recurrent Clostridium difficile infection (CDI), using a novel, standardized microbiota transplantation system.
Detailed Description
Clostridium difficile is an anaerobe, spore-forming bacillus. Infections with its toxin-producing strains are capable of causing CD associated enteral disease ranging in severity from mild diarrhea to fatal fulminant colitis. CD infection(CDI) occurs among patients who have taken antibiotics previously, suggesting that the normal gut flora is capable of preventing CDI. The disease is mainly treated with antibiotics, however, these antibiotics show high therapeutic failure and recurrence rates. There is significant interest in the development of alternative therapeutic strategies. Among the alternative methods only faecal microbiota transplantation (FMT) is gaining acceptance due to its excellent cure rate and low recurrence rate. FMT is a new approach to treating CDI, since no further antibiotics are administered, instead the normal gut flora being restored by administering faecal homogenisate from a healthy donor. Immediate risks of FMT are minimal, its efficacy is excellent,but further data is required about its short and long term safety, its most appropriate timing during the course of CDI and the optimal technical protocol for preparing the fecal homogenisate. In addition, the procedure is also challenging and the intervention itself is unappealing in nature. To address the challenges described above a novel faecal transplantation system has been designed (Burgin-Matic System, BMS), which is suitable for the production of faecal bacterial suspension in a standardized and controlled environment. Using this new approach, a multi-center,prospective,interventional clinical study involving two groups of patients has been designed: 1. In a non-randomized group("R") the safety and efficacy of FMT with the new, automated transplantation system will be assessed on 50 patients suffering from "R"ecurrent CDI. 2. In a randomized group ("F") FMT will be compared with the gold standard vancomycin treatment for 2x50 patients, with their "F"irst episode of CDI, suffering from severe infection or at risk of developing recurrent or severe disease and not responding to at least 72 hours of antibiotic treatment. In the non-randomized group("R"), the safety and efficacy of FMT will be assessed,with the hypothesis that FMT with the BMS is equally safe and effective(non-inferior)as reported in the international studies. In the randomized group ("F") primary endpoints will be the clinical cure rate at various time points, global cure rate at 10 weeks, time to clinical cure and time to global cure, while as secondary endpoints the cost effectiveness, quality of life, mortality will be assessed also. Our hypothesis is, that FMT with the BMS is superior to vancomycin treatment in terms of primary and secondary endpoints for these patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Group "R":- recurrent CDI;- positive stool toxin test within 72 hours before enrolment
- •Group "F":- first (initial) episode of CDI;- enrolled patient falls in at least one of the following categories:high risk of recurrence or high risk of developing severe CDI or severe or life-threatening CDI;- patient requires hospitalization or CDI occurs during a hospital stay;- persisting symptoms despite least 72 hours of adequate antibiotic treatment;-positive stool CD toxin test obtained within 72 hours before screening;- in all cases, primary consideration must be given to the severity and pace of the patient's CDI when deciding whether early use of FMT is appropriate to prevent further clinical deterioration.
Exclusion Criteria
- •absence of either patient's or its legally authorized representative's informed consent
- •inability or unwillingness to comply with protocol requirements
- •severe co-morbidities, terminal underlying disease with a life expectancy of less than 90 days
- •pregnancy or breastfeeding
- •active gastroenteritis caused by microorganisms other than CD
- •underlying chronic gastrointestinal disease that causes diarrhoea such as autonomic diabetic neuropathy, short bowel syndrome, faecal incontinence, active inflammatory bowel disease
- •alimentary or over-the-counter drog allergy with previous anaphylactic reaction
- •absolute contraindication to FMT
Arms & Interventions
Recurrent CDI FMT
Non-randomized group ("R") for treatment of recurrent CDI with FMT
Intervention: faecal human microbiota transplant (FMT)
Primary CDI antibiotic
Randomized group ("F" AB) for the treatment of primary CDI with antibiotics (vancomycin or fidaxomicin)
Intervention: Vancomycin or Fidaxomicin
Primary CDI FMT
Randomized group ("F" FMT) for the treatment of primary CDI with FMT
Intervention: faecal human microbiota transplant (FMT)
Outcomes
Primary Outcomes
Global cure rate at 10 weeks
Time Frame: 10 weeks after enrolment
Time to clinical cure
Time Frame: Through study completion, an average of 18 months
The number of days between enrolment and the resolution of diarrhoea
Time to global cure
Time Frame: Through study completion, an average of 18 months
The number of days between enrolment and the resolution of diarrhoea without relapse
Cure rate at 2 weeks
Time Frame: 2 weeks after enrolment
Cure rate at 4 weeks
Time Frame: 4 weeks after enrolment
Treatment failure rate
Time Frame: Through study completion, an average of 18 months
Recurrence rate 8 weeks after clinical cure
Time Frame: 8 weeks after clinical cure
Secondary Outcomes
- Number of adverse events (AE)(Through study completion, an average of 18 months)
- Number of serious adverse events (SAE)(Through study completion, an average of 18 months)
- Time of hospitalization(Through study completion, an average of 18 months)
- Days without diarrhoea during study period(Through study completion, an average of 18 months)
- Patient related quality of life(0, 7, 14 days after enrolment)
- Professional acceptance(Through study completion, an average of 18 months)
- General health survey for patients(0, 7, 14 days after enrolment)
- Patient anxiety and depression(0, 14, 70 days after enrolment)
- Patient acceptance of treatment(14,70 days after enrolment)