Clinical Trial to Demonstrate the Effectiveness of Fecal Microbiota Transplantation for Selective Intestinal Decolonization of Patients Colonized by Carbapenemase-producing Klebsiella Pneumoniae (KAPEDIS)

Randomized, Superiority, Double Blind Controlled With Placebo, Clinical Trial, to Demonstrate the Effectiveness of Fecal Microbiota Transplantation for Selective Intestinal Decolonization of Patients Colonized by Klebsiella Pneumoniae Carbapenemase (KPC)-Producing

Infections caused by carbapenemase-producing Enterobacteriaceae are frequent and often associated with high rates of mortality. Colonized patients are at increased risk of infection for these microorganisms. Moreover, they can act as a reservoir facilitating the transmission to other patients. To date, decolonization strategies with antibiotics have not obtained convincing results. For that reason our main objective is to investigate the efficacy of fecal microbiota transplantation (FMT) for selective intestinal decolonization of patients colonized by KPC-producing Klebsiella pneumoniae (Kp-KPC) at 30 days after FMT. Our hypothesis is that FMT is effective and safe for selective intestinal decolonization in patients colonized by Kp-KPC. The design of the study is a randomized, superiority, double blind controlled with placebo clinical trial.

The main variable is the percentage of patients with intestinal decolonization at 30 days after FMT in intention to treat population (all randomized patients). Decolonization will be considered as the abscence of isolation of Kp-KPC in culture from rectal swab together with the abscence of detection of carbapenemase by mean of polymerase chain reaction.

Secondary objectives are:

• To evaluate the safety of FMT.
• To determine if FMT is associated with decrease in the amount of bacteria at 7 days after FMT and 30 days after FMT.
• To evaluate if FMT is associated with persistent intestinal decolonization at 3 months after intervention.
• To study if FMT is associated with decrease in the incidence of Kp-KPC infections at 3 months after intervention.
• To evaluate if FMT is associated with decrease in mortality due to Kp-KPC infections at 3 months after intervention.

Study Overview

• Status: Recruiting
• Conditions: Carbapenemase-producing Enterobacteriaceae Infection
• Intervention / Treatment: Biological: Fecal microbiota transplantation; Other: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Juan José Castón Osorio, MD; Phone Number: 00 34 671 59 60 70; Email: juanjoco2005@yahoo.es
• Study Contact Backup: Name: Antonio Luque; Phone Number: (+34) 671 596 070; Email: uicec@imibic.org

Study Locations

• Spain
  • Cordoba, Spain, 14004
    • Recruiting
    • Hospital Universitario Reina Sofia
    • Contact: Juan Jose Caston Osorio, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age> = 18 years.
• Signature of the informed consent by the patient or legally designated person
• Absence of active infection by carbapenemase-type KPC-producing Klebsiella pneumoniae at the time of assessment as well as in the month prior to inclusion in the study

Exclusion Criteria:

• Terminal situation, or estimated life expectancy of less than 3 months
• Pregnant or lactating women
• Intolerance or inability to take oral medication at the time of assessment
• History of aspiration or dysphagia
• Patients with a history of colectomy, colostomy or ileostomy
• Patients who are receiving or have received antibiotics in the month prior to the inclusion assessment
• Neutrophil count less than 500 cells / mm3
• Anticipation of the use of myelosuppressive treatment (eg. dexamethasone, chemotherapy against to solid tumors or prior to transplantation of hematopoietic progenitories) within 30 days after inclusion in the study
• Hematopoietic stem cell transplantation in the month prior to inclusion in the study
• Presence of clinical signs of mucositis
• Forecast of major abdominal surgical intervention in the month following inclusion in the study
• Patients with a Gianella Score> 12 points
• History of having received decolonization guidelines in the previous 3 months
• Severe food allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Patients will receive four oral capsules containing placebo. These capsules will have the same shape, weight and colour as capsules containing FMT.
Experimental: Fecal microbiota transplantation	Biological: Fecal microbiota transplantation; Patients will receive four fecal microbiota transplantation (FMT) capsules. Microbiota is obtained from healthy patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decolonization	Percentage of patients with intestinal decolonization after receiving oral capsules of FMT or placebo in intention to treat population.	30 days after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with adverse effects	Percentage of patients with adverse effects	90 days after treatment.
Bacterial load	Amount of KPC-producing Klebsiella pneumoniae (Kp-KPC) after intervention	7 days and 30 days after treatment.
Persistent intestinal decolonization	Persistence of intestinal decolonization 90 days after intervention	90 days after treatment.
Infections caused by Kp-KPC	Percentage of patients with infections caused by Kp-KPC after intervention	90 days after treatment.
Mortality	Percentage of patients died after intervention	90 days after treatment.

Collaborators and Investigators

• Sponsor: Maimónides Biomedical Research Institute of Córdoba
• Collaborators: Mikrobiomik Healthcare Company S.L.
• Investigators: Principal Investigator: Juan José Castón Osorio, MD, Hospital Universitario Reina Sofia; Principal Investigator: Ángela Cano Yuste, MD, Hospital Universitario Reina Sofia

Publications and helpful links

General Publications

• Perez-Nadales E, Cano A, Recio M, Artacho MJ, Guzman-Puche J, Doblas A, Vidal E, Natera C, Martinez-Martinez L, Torre-Cisneros J, Caston JJ. Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS). BMJ Open. 2022 Apr 6;12(4):e058124. doi: 10.1136/bmjopen-2021-058124.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2021
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: February 15, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 18, 2021

Study Record Updates

• Last Update Posted (Estimate): March 3, 2023
• Last Update Submitted That Met QC Criteria: March 2, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: fecal microbiota transplantation; Klebsiella pneumoniae; decolonization; carbapenemase; intestinal colonization
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia; Enterobacteriaceae Infections; Klebsiella Infections
• Other Study ID Numbers: KAPEDIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: After publishing the results in a journal.
• IPD Sharing Access Criteria: Upon request to uicec@imibic.org
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

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