Heterogeneity of Randomized Controlled Trials of Fecal Microbiota Transplantation in Recurrent Clostridioides difficile Infection

Abstract

Introduction Clinical trials have demonstrated the efficacy of FMT for reduction in CDI recurrences (rCDI), but this treatment and its reporting in the literature has significant heterogeneity. Recent publications (e.g., Ramai et al. in Dig Dis Sci 2020.

Efficacy and Safety of RBX2660 in PUNCH CD3, a Phase III, Randomized, Double-Blind, Placebo-Controlled Trial with a Bayesian Primary Analysis for the Prevention of Recurrent Clostridioides difficile Infection

“…The higher threshold therefore corresponds to a statistically very persuasive finding. The lower threshold provides evidence of a statistically significant phase III trial (see ESM, pages [7][8][9][10][11].…”

“…Uncontrolled and controlled clinical trials report FMT as an effective treatment for rCDI [11]. While these foundational trials have indicated treatment success for microbiota restoration in patients with rCDI [12], they suffer from significant heterogeneity [11,13].…”

“…Uncontrolled and controlled clinical trials report FMT as an effective treatment for rCDI [11]. While these foundational trials have indicated treatment success for microbiota restoration in patients with rCDI [12], they suffer from significant heterogeneity [11,13]. Tariq et al conducted a systematic review and meta-analysis of FMT in CDI and found a 67.7% clinical cure rate in randomized trials [12], consistent with the success rates after a single RBX2660 dose using both approaches to borrowing [70.4% and 70.6% PUNCH CD3 was a randomized, double-blind, placebocontrolled, phase III study that demonstrated the superiority of RBX2660 compared with placebo in reducing CDI recurrence.…”

ADS024, a Bacillus velezensis strain, protects human colonic epithelial cells against C. difficile toxin-mediated apoptosis

“…Although fecal microbiota transplantation has shown a 90% success rate ( Borgia et al, 2015 ), additional efforts are needed to address safety concerns and other technical improvements ( Wang et al, 2016 ; Shin et al, 2018 ; DeFilipp et al, 2019 ). New preventive and therapeutic approaches are currently being developed as live biotherapeutic products (LBPs), including numerous capsule-based standardized microbiota restoration approaches ( Feuerstadt et al, 2021 ; Khanna et al, 2021 ).…”

Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm

“…The liver phenotype is based on histological features that also have similar presentations in humans ( Figure 1 ). Metabolic disorder phenotype describes various systemic disorders of the animal models that are also presented in MAFLD: (i) obesity refers to significantly increased body weight from control, (ii) diabetes, (iii) insulin resistance is tested via glucose tolerance tests, introduced intraperitoneally, intravenously or orally [ 170 ], and (iv) dyslipidemia refers to increased plasma cholesterol levels, increased plasma triglycerides, cholesterol, low-density lipoprotein (LDL) and/or decreased high-density lipoprotein (HDL). Due to the cumulative and temporal nature of the animal models, these characteristics are described in terms of the earliest duration of feeding reported in the model, from the start time of the model, that is, the time of diet initiation.…”