A Novel Faecal Microbiota Transplantation System for Treatment of Primary and Recurrent Clostridium Difficile Infection

Clostridium Difficile Infection Clinical Trial

— FMTREAT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03053505
• Other study ID #: FMT01
• Status: Recruiting
• Phase: N/A
• First received: January 18, 2017
• Last updated: March 29, 2017
• Start date: January 2017
• Est. completion date: October 2018

Study information

• Verified date: March 2017
• Source: Sejtterapia Kozpont Kft.
• Contact: Gergely G Nagy, M.D., Ph.D.
• Phone: 0036209547016
• Email: ngergely[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: October 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Clostridium Difficile Infection
• Communicable Diseases
• Infection

Intervention

Biological:
• faecal human microbiota transplant (FMT)
Non-randomized group "R": Patients with recurrent CD infection are treated with FMT in this group. Randomized group "F"FMT: patients with initial CD infection who have severe disease or who are at high risk of recurrence or high risk of developing severe disease are treated with FMT.

Drug:
• Vancomycin or Fidaxomicin
Randomized group "F"AB: patients with initial CD infection who have severe disease or who are at high risk of recurrence or high risk of developing severe disease are treated with antibiotics (vancomycin per os 125mg four times a day for 10 days) in this group. In case of treatment failure changes in antibiotic regime (e.g. fidaxomicin per os 200mg per two times a day for 10 days) will be allowed in the line with the recommendations of current CDI treatment guidelines(13).

Locations

Country	Name	City	State
Hungary	University of Debrecen, Clinical Centre	Debrecen	Hajdu-Bihar megye
Hungary	Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz	Miskolc	B-A-Z County
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza	Szabocs-Szatmar-Bereg megye

Sponsors (7)

Lead Sponsor	Collaborator
Sejtterapia Kozpont Kft.	Bacs-Kiskun Megyei Korhaz, Kenézy Gyula Korhaz es Rendelointezet, Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz, Szabolcs-Szatmar-Bereg Megyei Korhaz es Egyetemi Oktatokorhaz, UD-Genomed Kft., University of Debrecen

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global cure rate at 10 weeks		10 weeks after enrolment
Primary	Time to clinical cure	The number of days between enrolment and the resolution of diarrhoea	Through study completion, an average of 18 months
Primary	Time to global cure	The number of days between enrolment and the resolution of diarrhoea without relapse	Through study completion, an average of 18 months
Primary	Cure rate at 2 weeks		2 weeks after enrolment
Primary	Cure rate at 4 weeks		4 weeks after enrolment
Primary	Treatment failure rate		Through study completion, an average of 18 months
Primary	Recurrence rate 8 weeks after clinical cure		8 weeks after clinical cure
Secondary	Number of adverse events (AE)	Number of participants with treatment related adverse events	Through study completion, an average of 18 months
Secondary	Number of serious adverse events (SAE)	Number of participants with treatment related serious adverse events	Through study completion, an average of 18 months
Secondary	Time of hospitalization		Through study completion, an average of 18 months
Secondary	Days without diarrhoea during study period		Through study completion, an average of 18 months
Secondary	Patient related quality of life	Measured with EuroQoL 5Q-TL questionnaire	0, 7, 14 days after enrolment
Secondary	Professional acceptance	A modified TSQM-14 questionnaire for assessing professional acceptance will be used during the study	Through study completion, an average of 18 months
Secondary	General health survey for patients	Measured with SF-36v2 questionnaire	0, 7, 14 days after enrolment
Secondary	Patient anxiety and depression	Measured with HAD Scale (HADS)	0, 14, 70 days after enrolment
Secondary	Patient acceptance of treatment	Measure with TSQM-14 questionnaire	14,70 days after enrolment