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)

Elena Pérez-Nadales, Ángela Cano, Manuel Recio, María José Artacho, Julia Guzmán-Puche, Antonio Doblas, Elisa Vidal, Clara Natera, Luis Martínez-Martínez, Julian Torre-Cisneros, Juan José Castón, Elena Pérez-Nadales, Ángela Cano, Manuel Recio, María José Artacho, Julia Guzmán-Puche, Antonio Doblas, Elisa Vidal, Clara Natera, Luis Martínez-Martínez, Julian Torre-Cisneros, Juan José Castón

Abstract

Introduction: Infections caused by carbapenemase-producing Enterobacterales are frequent and associated with high rates of mortality. Intestinal carriers are at increased risk of infection by these microorganisms. Decolonisation strategies with antibiotics have not obtained conclusive results. Faecal microbiota transplantation (FMT) could be an effective and safe strategy to decolonise intestinal carriers of KPC-producing Klebsiella pneumoniae (KPC-Kp) but this hypothesis needs evaluation in appropriate clinical trials.

Methods and analysis: The KAPEDIS trial is a single-centre, randomised, double-blind, placebo-controlled, phase 2, superiority clinical trial of FMT for eradication of intestinal colonisation by KPC-Kp. One hundred and twenty patients with rectal colonisation by KPC-Kp will be randomised 1:1 to receive encapsulated lyophilised FMT or placebo. The primary outcome is KPC-Kp eradication at 30 days. Secondary outcomes are: (1) frequency of adverse events; (2) changes in KPC-Kp relative load within the intestinal microbiota at 7, 30 and 90 days, estimated by real-time quantitative PCR analysis of rectal swab samples and (3) rates of persistent eradication, KPC-Kp infection and crude mortality at 90 days. Participants will be monitored for adverse effects throughout the intervention.

Ethics and dissemination: Ethical approval was obtained from Reina Sofía University Hospital Institutional Review Board (approval reference number: 2019-003808-13). Trial results will be published in peer-reviewed journals and disseminated at national and international conferences.

Trial registration number: NCT04760665.

Keywords: infection control; infectious diseases; public health.

Conflict of interest statement

Competing interests: ‘Yes, there are competing interests for one or more authors and I have provided a Competing Interests statement in my manuscript and in the box below’

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Schedule of enrolment, interventions and assessments according to SPIRIT guidelines. FMT, faecal microbiota transplantation; KPC-Kp, KPC-producing Klebsiella pneumoniae; SPIRIT, Standard Protocol Items: Recommendations for Interventional Trials.1 If female and of child-bearing age. 2 Physical examination: weight, height, blood pressure, heart and respiratory rate and temperature. Does not apply if interview is conducted telephonically.3 Hemogram with at least hemoglobin, white blood cell count, neutrophils and platelets. Blood chemistry at least with creatinine, urea, bilirubin, transaminases and PCR.4 Serology for hepatitis A, B and C viruses; human immunodeficiency virus (HIV), HIV-1 and HIV-2; nontreponemal rapid plasma reagin (RPR) test, and fluorescent treponemal antibody absorbed (FTA-ABS) test.

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