Randomized Controlled Trial of Allogeneic Faecal Microbiota Transplantation for Postantibiotic Diarrhea in Critically Ill Patients

The primary objective of this study is to evaluate the **percentage of patients with treatment failure** at day 7 following randomisation in critically ill patients with postantibiotic diarrhoea. Treatment failure is defined as either the inability to administer the allocated treatment for any reason or the persistence of diarrhoea on day 7 post-randomisation. This objective is clinically relevant as it aims to assess the efficacy of the intervention in resolving diarrhoea, which is a significant concern in critically ill patients due to its potential to exacerbate their condition and prolong hospital stays.

Secondary objectives include assessing the composite number of adverse events such as new-onset sepsis, toxic megacolon, positive post faecal bacteriotherapy (FBT) blood culture, or other serious adverse events (SAEs) deemed possibly related to FBT by the attending physician. Additionally, the Sequential Organ Failure Assessment (SOFA) score will be evaluated on days 4 and 7. The study will also determine the percentage of patients who are recurrence-free at the time of hospital discharge or by day 28, whichever occurs earlier. Subgroup analyses will be conducted for patients who are positive versus negative for Clostridioides difficile and those who receive antibiotics for a new extra-abdominal infection versus those who do not.

The clinical trial focuses on **postantibiotic diarrhoea** in critically ill patients. The study population includes both male and female participants, aged over 18 years, who are in-patients in Intensive Care Units (ICU) or High Dependency Units (HDU), including burn units, and are expected to remain hospitalized for more than seven days. Participants are selected based on the presence of diarrhoea following antibiotic treatment, characterized by three or more stools per day or a Bristol type 7 stool with a volume exceeding 300 ml/day, persisting for 24 hours despite the cessation of enteral feeding formula. The trial involves a vulnerable population, as it includes critically ill patients. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **human faecal transplant** in treating **postantibiotic diarrhoea** in critically ill patients. This is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is set to run from March 2022 to December 2026, with the primary objective being the percentage of patients experiencing treatment failure by day 7 post-randomization. Treatment failure is defined as the inability to administer the allocated treatment or the persistence of diarrhoea on day 7.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as age over 18 years, current in-patient status in an ICU or HDU, and the presence of diarrhoea following antibiotic treatment. The inclusion visit will also involve obtaining informed consent. Follow-up visits will occur at specified intervals to monitor the primary and secondary endpoints, including adverse events and the Sequential Organ Failure Assessment (SOFA) score at days 4 and 7. The end-of-study visit will assess the recurrence-free status of patients at hospital discharge or by day 28, whichever occurs first.

Participant involvement is expected to last up to 28 days, with the possibility of early termination if the participant experiences severe adverse events or if the treatment is deemed ineffective. The trial will also conduct subgroup analyses to compare outcomes between patients who are positive or negative for **Clostridioides difficile** and those receiving antibiotics for new extra-abdominal infections versus those who do not. The trial's design and procedures are structured to ensure rigorous assessment of the treatment's safety and efficacy, contributing valuable data to the field of gastroenterology.

The clinical trial involves the administration of an **experimental medication** known as the **HUMAN FAECAL TRANSPLANT purified from allogeneic faecal donations**. This medication is formulated as a **gastroenteral suspension** and is intended for **intestinal** administration. The active substance in this treatment is **allogeneic faecal microbiota, pooled**, which is derived from structurally diverse substances. The maximum daily dose is 350 ml, with a total maximum dose of 700 ml over a treatment period of up to 2 days. The suspension is not a paediatric formulation and is not classified as an orphan drug. The administration of this treatment is monitored to ensure compliance with the dosing schedule.

In this study, there are no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments mentioned. The focus is solely on the efficacy and safety of the human faecal transplant in treating postantibiotic diarrhoea in critically ill patients. The trial aims to assess the percentage of patients experiencing treatment failure by day 7 post-randomisation, defined as either the inability to administer the allocated treatment or the persistence of diarrhoea.

Efficacy in the clinical trial titled "Faecal Bacteriotherapy for Postantibiotic Diarrhoea in Critically Ill Patients – Randomised Controlled Trial" will be assessed primarily by evaluating the **percentage of patients with treatment failure** at day 7 after randomisation. Treatment failure is defined as either the failure to administer the allocated treatment for any reason or the presence of diarrhoea on day 7 post-randomisation. This primary endpoint will provide a direct measure of the treatment's effectiveness in resolving postantibiotic diarrhoea.

Secondary endpoints include a composite number of adverse events such as new-onset sepsis, toxic megacolon, positive post-faecal bacteriotherapy (FBT) blood culture, or other serious adverse events (SAEs) assessed by the physician-in-charge as possibly related to FBT. Additionally, the Sequential Organ Failure Assessment (SOFA) score will be measured at days 4 and 7 to evaluate organ function. The percentage of patients that are recurrence-free at the time of hospital discharge or by day 28, whichever occurs earlier, will also be assessed. Subgroup analyses will be conducted for patients who are C. difficile positive versus negative and those who receive antibiotics for a new extra-abdominal infection versus those who do not.