Clinical trial NCT03053505: A Novel Faecal Microbiota Transplantation System for Treatment of Primary and Recurrent Clostridium Difficile Infection
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Clostridium Difficile Infection
Keywords: fecal microbiota transplantation (FMT)
Clostridium difficile infection
gut flora
human microbiome
colitis
Lead sponsor: Sejtterapia Kozpont Kft.
Sponsor class: INDUSTRY
Collaborators: name: University of Debrecen
name: Kenézy Gyula Korhaz es Rendelointezet
name: Szabolcs-Szatmar-Bereg Megyei Korhaz es Egyetemi Oktatokorhaz
name: Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz
name: Bacs-Kiskun Megyei Korhaz
name: UD-Genomed Kft.
First posted: 2017-02-15
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Global cure rate at 10 weeks
timeFrame: 10 weeks after enrolment
measure: Time to clinical cure
timeFrame: Through study completion, an average of 18 months
measure: Time to global cure
timeFrame: Through study completion, an average of 18 months
measure: Cure rate at 2 weeks
timeFrame: 2 weeks after enrolment
measure: Cure rate at 4 weeks
timeFrame: 4 weeks after enrolment
measure: Treatment failure rate
timeFrame: Through study completion, an average of 18 months
measure: Recurrence rate 8 weeks after clinical cure
timeFrame: 8 weeks after clinical cure
Secondary outcomes:
measure: Number of adverse events (AE)
timeFrame: Through study completion, an average of 18 months
measure: Number of serious adverse events (SAE)
timeFrame: Through study completion, an average of 18 months
measure: Time of hospitalization
timeFrame: Through study completion, an average of 18 months
measure: Days without diarrhoea during study period
timeFrame: Through study completion, an average of 18 months
measure: Patient related quality of life
timeFrame: 0, 7, 14 days after enrolment
measure: Professional acceptance
timeFrame: Through study completion, an average of 18 months
measure: General health survey for patients
timeFrame: 0, 7, 14 days after enrolment
measure: Patient anxiety and depression
timeFrame: 0, 14, 70 days after enrolment
measure: Patient acceptance of treatment
timeFrame: 14,70 days after enrolment
Other outcomes:
Locations:
city: Miskolc
country: Hungary
facility: Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz
state: B-A-Z County
city: Debrecen
country: Hungary
facility: University of Debrecen, Clinical Centre
state: Hajdu-Bihar megye
city: Nyiregyhaza
country: Hungary
facility: Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
state: Szabocs-Szatmar-Bereg megye
Study officials:
affiliation: University of Debrecen
name: Gergely G Nagy, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: University of Debrecen
name: Zoltan Szilvassy, M.D., D.Sc.
role: STUDY_DIRECTOR
affiliation: University of Debrecen
name: Gyorgy Paragh, M.D., D.Sc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kenezy Gyula Korhaz es Rendelointezet
name: Istvan Varkonyi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bacs-Kiskun Megyei Korhaz
name: Zoltan Fulep, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Szabolcs-Szatmar-Bereg Megyei Korhaz es Egyetemi Oktatokorhaz
name: Laszlo Szegedi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz
name: Tibor Pap, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: UD-Genomed Kft.
name: Laszlo Nagy, M.D., D.Sc.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kenezy Gyula Korhaz es Rendelointezet
name: Eva Rakoczi, M.D.
role: STUDY_CHAIR
affiliation: University of Debrecen
name: Judit Szabo, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: University of Debrecen
name: Maria Papp, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Sejtterapia Kozpont Kft.
name: Peter Vajo
role: PRINCIPAL_INVESTIGATOR
References: