## Protocol Section
### Identification Module
**NCT ID:** NCT05201079

**Brief Title:** Primary or Recurrent Clostridioides Difficile Infection Treatment With Capsules of Lyophilised Faecal Microbiota vs Fidaxomicin

**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.

#### Organization Study ID Info
**ID:** ICD-01
#### Organization
**Class:** INDUSTRY
**Full Name:** Mikrobiomik Healthcare Company S.L.
#### Secondary ID Infos
**ID:** 2020-004591-17
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2023-11-15

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-01-12

**Type:** ACTUAL

**Last Update Submit Date:** 2024-01-11

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2023-11-15

**Type:** ACTUAL

#### Start Date
**Date:** 2021-10-29

**Type:** ACTUAL

**Status Verified Date:** 2024-01

#### Study First Post Date
**Date:** 2022-01-21
**Type:** ACTUAL
**Study First Submit Date:** 2021-12-14
**Study First Submit QC Date:** 2022-01-20
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Mikrobiomik Healthcare Company S.L.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief 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.

**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:

* 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.

### Conditions Module

**Conditions:**

- Recurrent Clostridium Difficile Infection

- Primary Clostridium Difficile Infection

**Keywords:**

- Clostridium difficile

- FMT

- Fecal Microbiota Transfer

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 93

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants will receive MBK-01 capsules of fecal microbiota coming from healthy donors (33 patients).

**Intervention Names:**

- Biological: MBK-01

**Label:** MBK-01

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Participants will receive Fidaxomicin (33 patients).

**Intervention Names:**

- Drug: Dificlir

**Label:** Fidaxomicin

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- MBK-01

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

**Name:** MBK-01

**Other Names:**

- Fecal microbiota transfer

**Type:** BIOLOGICAL

#### Intervention 2

**Arm Group Labels:**

- Fidaxomicin

**Description:** Oral administration of 200mg/12 hours of fidaxomicin for 10 days.

**Name:** Dificlir

**Other Names:**

- Fidaxomicin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.

**Measure:** Global Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 8 weeks after the start of the treatment

**Time Frame:** 8 weeks after the start of the treatment

**Description:** Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.

**Measure:** Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 72 hours after the start of the treatment

**Time Frame:** 72 hours after the start of the treatment

**Description:** Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.

**Measure:** Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 3 weeks after the start of the treatment

**Time Frame:** 3 weeks after the start of the treatment

**Description:** Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.

**Measure:** Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 3 months after the start of the treatment

**Time Frame:** 3 months after the start of the treatment

**Description:** Diarrhea resolution: \<3 stools/24 hours for at least 2 consecutive days after the end of the treatment.

**Measure:** Absence of diarrhea: Number of episodes of diarrhea (3 or more stools/24 hours) 6 months after the start of the treatment

**Time Frame:** 6 months after the start of the treatment

#### Secondary Outcomes

**Description:** Time, in days, that the patient remains in the hospital as a result of CDI.

**Measure:** Duration of hospitalisation

**Time Frame:** Up to 8 weeks after the start of the treatment

**Description:** 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.

**Measure:** Good/bad progress of the patient

**Time Frame:** Up to 72 hours after the start of the treatment

**Description:** 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.

**Measure:** Time to recurrence depending on randomisation groups

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Duration in days of the treatment.

**Measure:** Duration of treatment

**Time Frame:** Up to 10 days

**Description:** Percentage of patients that are still alive after a defined period of time from the beginning of the treatment.

**Measure:** Overall survival

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Number of Adverse Events per randomisation group since baseline.

**Measure:** Number of Adverse Events per randomisation group

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Type of Adverse Events per ramdomisation group since baseline.

**Measure:** Type of Adverse Events per ramdomisation group

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Number of Serious Adverse Events per ramdomisation group since baseline.

**Measure:** Number of Serious Adverse Events per ramdomisation group

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Type of Serious Adverse Events per ramdomisation group since baseline.

**Measure:** Type of Serious Adverse Events per ramdomisation group

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Adverse Events related to the treatment since baseline.

**Measure:** Adverse Events related to the treatment

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Adverse Event Seriousness since baseline.

**Measure:** Adverse Event Seriousness

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Adverse Events related to the CDI since baseline.

**Measure:** Adverse Events related to the CDI

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Percentage of patients that die due to CDI after a defined period of time from the beginning of the treatment.

**Measure:** Mortality associated with CDI

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Percentage of patients admitted in the ICU after a defined period of time from the beginning of the treatment.

**Measure:** Intensive Care Unit admissions (ICU)

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** Adverse Events of special interest since baseline.

**Measure:** Adverse Events of special interest

**Time Frame:** Up to 6 months after the start of the treatment

**Description:** 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).

**Measure:** SF36 questionnaire (The Short Form-36 Health Survey) to evaluate the quality of life

**Time Frame:** Day 0, 8 weeks and 6 months after the start of the treatment

### Eligibility Module

**Eligibility Criteria:** 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.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Santander

**Country:** Spain

**Facility:** Hospital Universitario Marqués de Valdecilla

**State:** Cantabria

**Zip:** 39008

**Location 2:**

**City:** Alicante

**Country:** Spain

**Facility:** Hospital General Universitario de Alicante

**Zip:** 03010

**Location 3:**

**City:** Barakaldo

**Country:** Spain

**Facility:** Hospital Universitario de Cruces

**Zip:** 48903

**Location 4:**

**City:** Barcelona

**Country:** Spain

**Facility:** Hospital Quirónsalud Barcelona

**Zip:** 08023

**Location 5:**

**City:** Barcelona

**Country:** Spain

**Facility:** Hospital Clínic de Barcelona

**Zip:** 08036

**Location 6:**

**City:** Barcelona

**Country:** Spain

**Facility:** Hospital Universitario de Bellvitge

**Zip:** 08907

**Location 7:**

**City:** Bilbao

**Country:** Spain

**Facility:** Hospital Universitario de Basurto

**Zip:** 48013

**Location 8:**

**City:** Córdoba

**Country:** Spain

**Facility:** Hospital Universitario Reina Sofía

**Zip:** 14004

**Location 9:**

**City:** Donostia

**Country:** Spain

**Facility:** Hospital Universitario de Donostia

**Zip:** 20014

**Location 10:**

**City:** Girona

**Country:** Spain

**Facility:** Hospital Josep Trueta de Gerona

**Zip:** 17007

**Location 11:**

**City:** Logroño

**Country:** Spain

**Facility:** Hospital San Pedro

**Zip:** 26006

**Location 12:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital General Universitario Gregorio Marañón

**Zip:** 28007

**Location 13:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital Universitario Ramón y Cajal

**Zip:** 28034

**Location 14:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital Universitario 12 de Octubre

**Zip:** 28041

**Location 15:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital Universitario La Paz

**Zip:** 28046

**Location 16:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital Universitario Puerta de Hierro

**Zip:** 28222

**Location 17:**

**City:** Madrid

**Country:** Spain

**Facility:** Hospital Universitario Quirónsalud Madrid

**Zip:** 28223

**Location 18:**

**City:** Palma De Mallorca

**Country:** Spain

**Facility:** Hospital Universitario Son Espases

**Zip:** 07120

**Location 19:**

**City:** Valencia

**Country:** Spain

**Facility:** Hospital Universitario y Politécnico La Fe

**Zip:** 46026

**Location 20:**

**City:** Vitoria-Gasteiz

**Country:** Spain

**Facility:** Hospital Universitario de Araba

**Zip:** 01009

**Location 21:**

**City:** Zaragoza

**Country:** Spain

**Facility:** Hospital Clínico Universitario Lozano Blesa

**Zip:** 50009

#### Overall Officials

**Official 1:**

**Affiliation:** Hospital Universitario Ramon y Cajal

**Name:** Javier Cobo, MD

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### References

**Citation:** 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.

**PMID:** 31883938

**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.

**PMID:** 30221898

#### See Also Links

**Label:** EU Clinical Trials Register

**URL:** https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-004591-17/ES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000016908

- Term: Gram-Positive Bacterial Infections

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M6368

- Name: Communicable Diseases

- Relevance: HIGH

- As Found: Infection

- ID: M14850

- Name: Recurrence

- Relevance: HIGH

- As Found: Recurrent

- ID: M6247

- Name: Clostridium Infections

- Relevance: HIGH

- As Found: Clostridium Difficile Infection

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M19252

- Name: Gram-Positive Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000003141

- Term: Communicable Diseases

- ID: D000003015

- Term: Clostridium Infections

- ID: D000012008

- Term: Recurrence

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1890

- Name: Fidaxomicin

- Relevance: HIGH

- As Found: Aneurysm Repair

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077732

- Term: Fidaxomicin

### Misc Info Module

- Version Holder: 2024-05-24
