Treatment of CDI and Recurrence With Fecal Microbiota Transplant Using Promicrobioma

Randomized Controlled Clinical Study of Treatment of Clostridioides Difficile Infection Comparing Fecal Microbiota Transplantation With Antibiotic Treatment

The increasing inappropriate use of antimicrobials, in addition to increasing selective pressure and inducing environmental resistance, is also a risk factor for the development of Clostridioides difficile infection (CDI). The intestinal microbiota is mainly composed of the phyla Firmicutes, Bacteroidetes, Acinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia, and more than 90% of the phylum Firmicutes is composed of Clostridium spp. (two). The inappropriate use of antimicrobials initiates a process of dysregulation of the microbiome, called dysbiosis, and it is from the selection of genera and species of bacteria that will dominate the intestine that pseudomembranous colitis can set in with an increased burden of Clostridioides difficile, a gram positive, anaerobic, spore-forming, that produces two enterotoxins, toxin A and toxin.

Study Overview

• Status: Not yet recruiting
• Conditions: Clostridium Difficile Infections
• Intervention / Treatment: Other: Fecal microbiota transplant (Promicrobioma); Drug: Antibiotic

Detailed Description

INTRODUCTION

The increasing inappropriate use of antimicrobials, in addition to increasing selective pressure and inducing environmental resistance, is also a risk factor for the development of Clostridioides difficile infection (CDI). The intestinal microbiota is mainly composed of the phyla Firmicutes, Bacteroidetes, Acinobacteria, Proteobacteria, Fusobacteria and Verrucomicrobia, and more than 90% of the phylum Firmicutes is composed of Clostridium spp. (two). The inappropriate use of antimicrobials initiates a process of dysregulation of the microbiome, called dysbiosis, and it is from the selection of genera and species of bacteria that will dominate the intestine that pseudomembranous colitis can set in with an increased burden of Clostridioides difficile, a gram positive, anaerobic, spore-forming, that produces two enterotoxins, toxin A and toxin.

Currently, pseudomembranous colitis has few treatment options: the main one is fidaxomicin, unavailable in Brazil, and other alternatives are vancomycin and metronidazole. However, refractoriness to alternative treatments may occur, with fecal transplantation also being an alternative. Additionally, fecal transplantation is often associated with better outcomes than drug alternatives, reaching more than 90% clinical success.

Fecal microbiota transplantation (FMT) can occur through different routes, for example, via nasoenteral tube, colonoscopy, oral capsules or enemas, with colonoscopy or capsules normally being apparently more effective than enemas and nasoenteral tubes. Furthermore, the preparation of stool samples can be either fresh or frozen, which do not influence the effectiveness of the treatment. Since 2020, the PUCPR Fecal Microbiota Bank has been carrying out validation studies of a product, PROMICROBIOMA, composed of freeze-dried human fecal microbiota, which has already tested its safety in a phase 1 study on consecutive patients in a convenience sample. To evaluate the effectiveness of the product, it is important to carry out a controlled and randomized clinical study comparing it with antimicrobial therapy.

HYPOTHESIS H0 - PROMICROBIOMA is equal to antibiotic treatment in primary or recurrent CDI H1 - PROMICROBIOME is superior to antibiotic treatment in primary or recurrent CDI H2 - PROMICROBIOME is inferior to antibiotic treatment in primary or recurrent CDI

MAIN GOAL

To evaluate the clinical outcome of patients with primary or recurrent CDI using PROMICROBIOMA compared to antimicrobial therapy.

METHODS

Study design

This is a randomized, controlled clinical study of patients with primary or recurrent CDI.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

The inclusion criteria are:

1. Over 18 years old;
2. Hospitalized patients;
3. Clinical and laboratory diagnosis of CDI;
4. Signing the informed consent form
5. For primary CDI, use of antibiotics for less than 72 hours; and for recurrent CDI, previous confirmed CDI with clinical response to antibiotic treatment and CDI recurrence within 8 weeks.

The exclusion criteria are:

1. Pregnant patients
2. Severe form of CDI requiring surgery
3. Impossibility of performing the colonoscopy procedure or using a nasoenteral tube

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: Promicrobioma; MIcrobiote tranplant	Other: Fecal microbiota transplant (Promicrobioma); Fecal microbiota transplant with Promicrobioma (freeze-dried isolated microbiota)
Active Comparator: Antibiotic (metronidazole or vancomycin); Antibiotic commonly used for treatment of CDI, including oral vancomycin or metronidazol)	Drug: Antibiotic; Antibiotics for Clostridioides infection (oral vancomycin) or association of intravenous metronidazol for severe cases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical cure rate	Clinical cure is defined as absence of diarrhea, abdominal pain, clinical signs of infection (fever).	8 weeks

Collaborators and Investigators

• Sponsor: Hospital Universitario Evangelico de Curitiba

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 24, 2023
• First Posted (Actual): October 30, 2023

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Clostridium Infections; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: CDItransplant

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No