A randomized controlled trial of precision bezlotoxumab treatment for Clostridioides difficile infection.

Abstract

Early risk recognition for organ dysfunction and death by Clostridioides difficile infection (CDI) is an unmet need. A prediction score is developed in the BEYOND study (ClinicalTrials.gov; NCT02573571, NCT04725123, and NCT05304715). At the first stage, using 153 patients and 150 comparators, the BEYOND score was developed integrating hemoglobin; blood urea; blood interleukin-8; carriage of G alleles of rs2091172; and presence of Terrisporobacter glycolicus, Enterococcus avium, and Anaerovorax odorimutans in the stool. The score had 84.6% sensitivity and 95.8% specificity for unfavorable outcomes. At the second stage, a double-blind randomized controlled trial was performed, and 44 patients at high-risk by BEYOND score were treated with standard-of-care plus Bezlotoxumab or placebo. The primary endpoint was the incidence of organ dysfunction, CDI relapse, and/or death. This endpoint was met in 72.7% of patients in the placebo arm and 31.8% in the Bezlotoxumab arm (p = 0.015). Results suggest that BEYOND score can detect early risk in patients with CDI.