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)

Abstract

IntroductionInfections 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 analysisThe 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 disseminationEthical 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 numberNCT04760665.

Past, present, and future of microbiome-based therapies

“…To support the development of complex microbiome-based therapies, the existence of stool banks is increasing worldwide [141] . Similar to how organ donations work, stool banks can coordinate donations from healthy individuals, perform thorough donor and sample screening to ensure product safety, store samples in adequate conditions, and provide the material to companies developing such products upon request.…”

“…Because FMT success in CDI is driven, at least in part, by competition for nutritional resources, there are several CTs testing FMT potential to reduce or ablate colonization of the intestinal tract with multiresistant bacteria. So far, a reduction in recurrent infections of > 50% has been demonstrated [ 131 , 142 ] . In a similar way, modulating the native healthy vaginal microbiome is being used to improve women’s health.…”

Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages?

“…A first multi-centric randomized clinical trial including 39 patients failed to obtain statistically significant results due to early termination of the study despite a slightly decreased of ESBL and/or carbapenemase producing Enterobacterales colonization compared to the control group: 41% of the patients colonized were negative at day 35-48 compared to 29% of the patients of the control group (Huttner et al, 2019). A second randomized double blind trial study against placebo (KAPEDIS) regarding the efficacy of decolonization of KPC producing K. pneumoniae is currently ongoing (Perez-Nadales et al, 2022). So far, according to Merrick et al 13 randomized studies are actually ongoing or have been recently completed (Merrick et al, 2023).…”