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

Recurrent Clostridium Difficile Infection Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05201079
• Other study ID #: ICD-01
• Secondary ID: 2020-004591-17
• Status: Completed
• Phase: Phase 3
• Start date: October 29, 2021
• Est. completion date: November 15, 2023

Study information

• Verified date: January 2024
• Source: Mikrobiomik Healthcare Company S.L.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 66 patients with primary or r-CDI.

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:

• Dificlir (Fidaxomicina)

• 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. To 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, supporting 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: November 15, 2023
• Est. primary completion date: November 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Infections
• Communicable Diseases
• Infections
• Recurrence
• Recurrent Clostridium Difficile Infection

Intervention

Biological:
• MBK-01
A single dose of 4 capsules of MBK-01 (heterologous lyophilized fecal microbiota coming from healthy donors) orally.

Drug:
• Dificlir
Oral administration of 200mg/12 hours of fidaxomicin for 10 days.

Locations

Country	Name	City	State
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Universitario de Cruces	Barakaldo
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Quirónsalud Barcelona	Barcelona
Spain	Hospital Universitario de Bellvitge	Barcelona
Spain	Hospital Universitario de Basurto	Bilbao
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario de Donostia	Donostia
Spain	Hospital Josep Trueta de Gerona	Girona
Spain	Hospital San Pedro	Logroño
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Puerta de Hierro	Madrid
Spain	Hospital Universitario Quirónsalud Madrid	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Hospital Universitario Son Espases	Palma De Mallorca
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Universitario de Araba	Vitoria-Gasteiz
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Mikrobiomik Healthcare Company S.L.

Country where clinical trial is conducted

Spain, 

References & Publications (2)

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 8 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.	8 weeks after the start of the treatment
Primary	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
Primary	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
Primary	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
Primary	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	Duration of hospitalisation	Time, in days, that the patient remains in the hospital as a result of CDI.	Up to 8 weeks after the start of the treatment
Secondary	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
Secondary	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
Secondary	Duration of treatment	Duration in days of the treatment.	Up to 10 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Adverse Events related to the treatment	Adverse Events related to the treatment since baseline.	Up to 6 months after the start of the treatment
Secondary	Adverse Event Seriousness	Adverse Event Seriousness since baseline.	Up to 6 months after the start of the treatment
Secondary	Adverse Events related to the CDI	Adverse Events related to the CDI since baseline.	Up to 6 months after the start of the treatment
Secondary	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
Secondary	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
Secondary	Adverse Events of special interest	Adverse Events of special interest since baseline.	Up to 6 months after the start of the treatment
Secondary	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

External Links

•   EU Clinical Trials Register