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

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

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.

Study Overview

• Status: Unknown
• Conditions: Clostridium Difficile Infection
• Intervention / Treatment: Biological: faecal human microbiota transplant (FMT); Drug: Vancomycin or Fidaxomicin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gergely G Nagy, M.D., Ph.D.; Phone Number: 0036209547016; Email: ngergely@hotmail.com
• Study Contact Backup: Name: Zsuzsa Tudlik, Pharm.D.; Phone Number: 0036204197188; Email: drtudlikzsuzsa@sejtterapia.hu

Study Locations

• Hungary
  • B-A-Z County
    • Miskolc, B-A-Z County, Hungary, 3525
      • Recruiting
      • Miskolci Semmelweis Kórház és Egyetemi Oktatókórház
      • Contact: Tibor Pap, M.D.
  • Hajdu-Bihar megye
    • Debrecen, Hajdu-Bihar megye, Hungary, 4032
      • Recruiting
      • University of Debrecen, Clinical Centre
      • Contact: Gyorgy Paragh, M.D., D.Sc.
  • Szabocs-Szatmar-Bereg megye
    • Nyiregyhaza, Szabocs-Szatmar-Bereg megye, Hungary, 4400
      • Recruiting
      • Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
      • Contact: Laszlo Szegedi, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recurrent CDI FMT; Non-randomized group ("R") for treatment of recurrent CDI with FMT	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.; Other Names: FMT
Active Comparator: Primary CDI antibiotic; Randomized group ("F" AB) for the treatment of primary CDI with antibiotics (vancomycin or fidaxomicin)	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).
Experimental: Primary CDI FMT; Randomized group ("F" FMT) for the treatment of primary CDI with FMT	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.; Other Names: FMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global cure rate at 10 weeks		10 weeks after enrolment
Time to clinical cure	The number of days between enrolment and the resolution of diarrhoea	Through study completion, an average of 18 months
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
Cure rate at 2 weeks		2 weeks after enrolment
Cure rate at 4 weeks		4 weeks after enrolment
Treatment failure rate		Through study completion, an average of 18 months
Recurrence rate 8 weeks after clinical cure		8 weeks after clinical cure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AE)	Number of participants with treatment related adverse events	Through study completion, an average of 18 months
Number of serious adverse events (SAE)	Number of participants with treatment related serious adverse events	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	Measured with EuroQoL 5Q-TL questionnaire	0, 7, 14 days after enrolment
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
General health survey for patients	Measured with SF-36v2 questionnaire	0, 7, 14 days after enrolment
Patient anxiety and depression	Measured with HAD Scale (HADS)	0, 14, 70 days after enrolment
Patient acceptance of treatment	Measure with TSQM-14 questionnaire	14,70 days after enrolment

Collaborators and Investigators

• Sponsor: Sejtterapia Kozpont Kft.
• Collaborators: University of Debrecen; Kenézy Gyula Korhaz es Rendelointezet; Szabolcs-Szatmar-Bereg Megyei Korhaz es Egyetemi Oktatokorhaz; Miskolci Semmelweis Korhaz es Egyetemi Oktatokorhaz; Bacs-Kiskun Megyei Korhaz; UD-Genomed Kft.
• Investigators: Study Chair: Gergely G Nagy, M.D., Ph.D., University of Debrecen; Study Director: Zoltan Szilvassy, M.D., D.Sc., University of Debrecen; Principal Investigator: Gyorgy Paragh, M.D., D.Sc., University of Debrecen; Principal Investigator: Istvan Varkonyi, M.D., Kenézy Gyula Kórház És Rendelőintézet; Principal Investigator: Zoltan Fulep, M.D., Bacs-kiskun Megyei Korhaz; Principal Investigator: Laszlo Szegedi, M.D., Szabolcs-Szatmar-Bereg Megyei Korhaz es Egyetemi Oktatokorhaz; Principal Investigator: Tibor Pap, M.D., Miskolci Semmelweis Kórház és Egyetemi Oktatókórház; Principal Investigator: Laszlo Nagy, M.D., D.Sc., UD-Genomed Kft.; Study Chair: Eva Rakoczi, M.D., Kenézy Gyula Kórház És Rendelőintézet; Study Chair: Judit Szabo, M.D., Ph.D., University of Debrecen; Study Chair: Maria Papp, M.D., Ph.D., University of Debrecen; Principal Investigator: Peter Vajo, Sejtterapia Kozpont Kft.

Study record dates

Study Major Dates

• Study Start: January 1, 2017
• Primary Completion (Anticipated): December 1, 2017
• Study Completion (Anticipated): October 1, 2018

Study Registration Dates

• First Submitted: January 18, 2017
• First Submitted That Met QC Criteria: February 10, 2017
• First Posted (Actual): February 15, 2017

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Clostridium difficile infection; colitis; fecal microbiota transplantation (FMT); gut flora; human microbiome
• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents; Vancomycin; Fidaxomicin
• Other Study ID Numbers: FMT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided