Primary or Recurrent Clostridioides Difficile Infection Treatment With Capsules of Lyophilised Faecal Microbiota vs Fidaxomicin

A Randomised, Controlled, Open-label Phase III Clinical Trial in Patients With Primary or Recurrent Clostridioides Difficile (CD) Infection, to Evaluate the Efficacy and Safety of Capsules of Lyophilised Faecal Microbiota vs Fidaxomicin.

Patients with microbiota alterations developed after being exposed to antibiotics are especially susceptible to Clostridioides difficile infections (CDI). The incidence and severity of CDI has increased in recent years and CDI recurrences (r-CDI) due to the appearance of new episodes in patients with a previous cured CDI, represent a serious and complex clinical issue. Although antibiotics are the recommended therapy for the first episode of CDI, treatment with oral vancomycin and/or metronidazole often results in significant treatment failure. In addition, the treatment of r-CDI is not adequately standardized, and although the most widely used treatment is the administration of fidaxomicin and bezlotoxumab, its efficacy in patients who already have r-CDI is not proven. In the late years, Fecal Microbiota Transfer (FMT) has emerged as the preferred non-pharmacological treatment to manage CDI with multiple recurrences and recent clinical trials have evaluated its potential efficacy and safety in the treatment of patients with primary CD infection.

The objective of this study is to assess the efficacy and safety of the MBK-01 medication, consisting of heterologous lyophilized fecal microbiota capsules coming from healthy donors in comparison to the treatment with fidaxomicin, in 92 patients with primary or r-CDI.

Study Overview

• Status: Completed
• Conditions: Recurrent Clostridium Difficile Infection; Primary Clostridium Difficile Infection
• Intervention / Treatment: Biological: MBK-01; Drug: Fidaxomicin

Detailed Description

This is a Phase III, multicenter, controlled and open label clinical trial in which patients who suffered an episode of Clostridioides difficile infection (either the first episode or subsequent recurrences) will be randomly assigned (1:1) to one of the following arms:

• Fidaxomicin
• MBK-01 (heterologous lyophilized fecal microbiota)

Objective: To assess the efficacy of FMT with capsules of lyophilized fecal microbiota (MBK-01), compared to the control (fidaxomicin) at 8 weeks after the start of the treatment. Also, assess the safety of MBK-01 and the quality of life of patients participating in the study.

Follow up: participants will return for clinic visits at 72 hours, week 3 and week 8 after the start of the treatment, and will receive follow-up phone calls at month 3 and month 6 after the start of the treatment. Stool samples will be collected from participants for further studies at time 0 and week 8 after the start of the treatment. Study Outcomes are detailed in the specific section of this website.

Rationale: The transferred microbiota restores the recipient's intestinal microbiota by reintroducing bacterial taxa that were absent or in low proportion in the recipient before the FMT. This supports the expansion of the recipient's own commensal microbiota and re-establishing a microbiota community with a high biodiversity.

Donors: All donors are screened to ensure they meet the strict requirements necessary to maintain the safety of the MBK-01.

Justification: The treatment of Clostridioides difficile infections (CDI) with antibiotics is usually effective for acute symptoms, but after the initial treatment, the probability of recurrence at 8 weeks ranges from 10-20 % of cases, and once a patient has a recurrence, the probability of further recurrences increases up to 40-65 %. In recent years, Fecal Microbiota Transfer (FMT) has emerged as the preferred non-pharmacological treatment to manage CDI with multiple recurrences and recent clinical trials have evaluated its potential efficacy and safety in the treatment of patients with primary CD infection. Although antibiotics are the recommended therapy for the first episode of CDI, treatment with oral vancomycin and/or metronidazole often results in significant treatment failure, with recurrences occurring in up to 30-40% of patients. Furthermore, antibiotic treatment does not correct deficiencies in the intestinal microbiota that facilitate CD infection and is associated with the risk of the emergence of antibiotic-resistant bacteria. Moreover, the treatment of recurrences is not adequately standardized. In recent years, although the most widely used alternatives have been fidaxomicin and bezlotoxumab, their efficacy in patients who already suffer from r-CDI is not proven. The administration of the FMT through oral capsules, although it is not standardized, has proven to be effective in the restoration of intestinal microbiota of patients with r-CDI. In addition, the use of lyophilized formulas facilitates the concentration of bacteria and further optimizes the donors' sample and reduces the amount of capsules that the patient has to ingest.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barakaldo, Spain, 48903
    • Hospital Universitario de Cruces
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08023
    • Hospital Quironsalud Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Bilbao, Spain, 48013
    • Hospital Universitario de Basurto
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Donostia, Spain, 20014
    • Hospital Universitario DE Donostia
  • Girona, Spain, 17007
    • Hospital Josep Trueta de Gerona
  • Logroño, Spain, 26006
    • Hospital San Pedro
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain, 28223
    • Hospital Universitario Quironsalud Madrid
  • Palma De Mallorca, Spain, 07120
    • Hospital Universitario Son Espases
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
  • Vitoria-Gasteiz, Spain, 01009
    • Hospital Universitario de Araba
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Universitario Marques de Valdecilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients of both genders, over 18 years.
2. Patients that undergo an episode of CD infection (either the first episode or subsequent recurrences).
3. Presence of an episode of diarrhea defined as ≥3 stools/24 hours, at the beginning of the episode.
4. Confirmation of the presence of CD toxin A and/or B in faeces, by a direct toxin detection test or by the PCR technique for the detection of toxin/s producing genes, at the start of the episode that is going to be treated in the clinical trial (the toxin test must be positive within 7 days prior to the enrolment of the patient in the trial).

Exclusion Criteria:

1. Previous faecal microbiota transfer.
2. Transplanted patients, except those with a solid organ transplant of more than 2 years, with good organ function.
3. Absolute neutrophil count <500 cells /μL at the time of the enrollment in the study.
4. Pregnancy, breastfeeding, or pregnancy intentions over the course of the study.
5. Active treatment with bile acid sequestrants (for instance: cholestyramine).
6. Positive patients for the human immunodeficiency virus (HIV) except those with lymphocytes T CD4 count > 200 cells/μL and viral load less than 20 copies.
7. Swallowing dysfunction or no oral motor coordination.
8. Patient admitted in an intensive care unit or expected to be admitted in an intensive care unit due to serious illness.
9. History of significant medical conditions that, in the opinion of the investigator, would not allow an adequate evaluation or follow-up of the patient.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MBK-01; Participants will receive MBK-01 capsules of fecal microbiota coming from healthy donors (45 patients).	Biological: MBK-01; A single dose of 4 capsules of MBK-01 (heterologous lyophilized fecal microbiota coming from healthy donors) orally.; Other Names: Fecal microbiota transfer
Active Comparator: Fidaxomicin; Participants will receive Fidaxomicin (47 patients).	Drug: Fidaxomicin; Oral administration of 200mg/12 hours of fidaxomicin for 10 days.; Other Names: Dificid; Dificlir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Absence of Diarrhea Due to Clostridiodes Difficile 8 Weeks After the Start of the Treatment	Number of patients who showed recurrence of at least one Episode of Diarrhea (3 or More Stools/24 Hours) 8 Weeks After the Start of the Treatment. Recurrence is understood as the reappearance of clinical manifestations of a new episode of CDI that re-occurs within 8 weeks after the onset of symptoms of a previous episode that was resolved.	8 weeks after the start of the treatment
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 72 Hours After the Start of the Treatment	Diarrhea resolution: <3 stools/24 hours for at least 2 consecutive days after the end of the treatment.	72 hours after the start of the treatment
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 3 Weeks After the Start of the Treatment	Diarrhea resolution: <3 stools/24 hours for at least 2 consecutive days after the end of the treatment.	3 weeks after the start of the treatment
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 3 Months After the Start of the Treatment	Diarrhea resolution: <3 stools/24 hours for at least 2 consecutive days after the end of the treatment.	3 months after the start of the treatment
Absence of Diarrhea: Number of Episodes of Diarrhea (3 or More Stools/24 Hours) 6 Months After the Start of the Treatment	Diarrhea resolution: <3 stools/24 hours for at least 2 consecutive days after the end of the treatment.	6 months after the start of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Event Seriousness	Adverse Event Seriousness since baseline.	Up to 6 months after the start of the treatment
Duration of Hospitalisation	Time, in days, that the patient remains in the hospital as a result of CDI (but not necessarily indicating a recurrence of diarrhea due to CDI).	Up to 8 weeks after the start of the treatment
Good/Bad Progress of the Patient	A bad progress of the patient is defined as the detection 48-72 hours after the start of the treatment (MBK-01 or Fidaxomicin) of: A worsening of the diarrhea episode (at least one stool more than at baseline, baseline being understood as the time of the start of the study treatment (fidaxomicin or MBK01)). And, at least, one of the following factors: Increase in C-reactive protein (CRP) value (> 5 % of the baseline value).; Increase in white blood cell count (> 5 % of the baseline value).; Progression to sepsis: hypotension or organ failure with no other apparent cause.	Up to 72 hours after the start of the treatment
Time to Recurrence Depending on Randomisation Groups	Recurrence: Reappearance of clinical manifestations of a new CDI episode in a patient with an CDI episode treated and cured in the previous 8 weeks.	Up to 6 months after the start of the treatment
Duration of Treatment	Duration in days of the treatment.	Up to 10 days
Overall Survival	Percentage of patients that are still alive after a defined period of time from the beginning of the treatment.	Up to 6 months after the start of the treatment
Number of Adverse Events Per Randomisation Group	Number of Adverse Events per randomisation group since baseline.	Up to 6 months after the start of the treatment
Type of Adverse Events Per Ramdomisation Group	Type of Adverse Events per ramdomisation group since baseline.	Up to 6 months after the start of the treatment
Number of Serious Adverse Events Per Ramdomisation Group	Number of Serious Adverse Events per ramdomisation group since baseline.	Up to 6 months after the start of the treatment
Type of Serious Adverse Events Per Ramdomisation Group	Type of Serious Adverse Events per ramdomisation group since baseline.	Up to 6 months after the start of the treatment
Adverse Events Related to the Treatment	Adverse Events related to the treatment since baseline.	Up to 6 months after the start of the treatment
Adverse Events Related to the CDI	Adverse Events related to the CDI since baseline.	Up to 6 months after the start of the treatment
Mortality Associated With CDI	Percentage of patients that die due to CDI after a defined period of time from the beginning of the treatment.	Up to 6 months after the start of the treatment
Intensive Care Unit Admissions (ICU)	Percentage of patients admitted in the ICU after a defined period of time from the beginning of the treatment.	Up to 6 months after the start of the treatment
Adverse Events of Special Interest	Adverse Events of special interest since baseline.	Up to 6 months after the start of the treatment
SF36 Questionnaire (The Short Form-36 Health Survey) to Evaluate the Quality of Life	For each dimension (physical functioning, role limits-physical, bodily pain, general health, vitality, social functioning, role limits-emotional, mental health), the scale ranges from 0 (the worst health status for that dimension) to 100 (the best health status).	Day 0, 8 weeks and 6 months after the start of the treatment

Collaborators and Investigators

• Sponsor: Mikrobiomik Healthcare Company S.L.
• Investigators: Principal Investigator: Javier Cobo, MD, Hospital Universitario Ramon y Cajal

Publications and helpful links

General Publications

• Reigadas E, Bouza E, Olmedo M, Vazquez-Cuesta S, Villar-Gomara L, Alcala L, Marin M, Rodriguez-Fernandez S, Valerio M, Munoz P. Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules. J Hosp Infect. 2020 Jun;105(2):319-324. doi: 10.1016/j.jhin.2019.12.022. Epub 2019 Dec 26.
• Reigadas E, Olmedo M, Valerio M, Vazquez-Cuesta S, Alcala L, Marin M, Munoz P, Bouza E. Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results. Rev Esp Quimioter. 2018 Oct;31(5):411-418. Epub 2018 Sep 14.

Helpful Links

• EU Clinical Trials Register

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2021
• Primary Completion (Actual): November 15, 2023
• Study Completion (Actual): November 15, 2023

Study Registration Dates

• First Submitted: December 14, 2021
• First Submitted That Met QC Criteria: January 20, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Clostridium difficile; FMT; Fecal Microbiota Transfer
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Recurrence; Infections; Communicable Diseases; Clostridium Infections; Anti-Bacterial Agents; Anti-Infective Agents; Fidaxomicin
• Other Study ID Numbers: ICD-01; 2020-004591-17 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No