Publication
Title
A randomized, double-blind, phase 3 safety and efficacy study of ridinilazole versus vancomycin for treatment of Clostridioides difficile infection : clinical outcomes with microbiome and metabolome correlates of response
Author
Abstract
Background Exposure to antibiotics predisposes to dysbiosis and Clostridioides difficile infection (CDI) that can be severe, recurrent (rCDI), and life-threatening. Nonselective drugs that treat CDI and perpetuate dysbiosis are associated with rCDI, in part due to loss of microbiome-derived secondary bile acid (SBA) production. Ridinilazole is a highly selective drug designed to treat CDI and prevent rCDI.Methods In this phase 3 superiority trial, adults with CDI, confirmed with a stool toxin test, were randomized to receive 10 days of ridinilazole (200 mg twice daily) or vancomycin (125 mg 4 times daily). The primary endpoint was sustained clinical response (SCR), defined as clinical response and no rCDI through 30 days after end of treatment. Secondary endpoints included rCDI and change in relative abundance of SBAs.Results Ridinilazole and vancomycin achieved an SCR rate of 73% versus 70.7%, respectively, a treatment difference of 2.2% (95% CI: -4.2%, 8.6%). Ridinilazole resulted in a 53% reduction in recurrence compared with vancomycin (8.1% vs 17.3%; 95% CI: -14.1%, -4.5%; P = .0002). Subgroup analyses revealed consistent ridinilazole benefit for reduction in rCDI across subgroups. Ridinilazole preserved microbiota diversity, increased SBAs, and did not increase the resistome. Conversely, vancomycin worsened CDI-associated dysbiosis, decreased SBAs, increased Proteobacteria abundance (similar to 3.5-fold), and increased the resistome.Conclusions Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566.Conclusions Although ridinilazole did not meet superiority in SCR, ridinilazole greatly reduced rCDI and preserved microbiome diversity and SBAs compared with vancomycin. These findings suggest that treatment of CDI with ridinilazole results in an earlier recovery of gut microbiome health. Clinical Trials Registration.Ri-CoDIFy 1 and 2: NCT03595553 and NCT03595566. In this phase 3 superiority study, ridinilazole, bactericidal bis-benzimidazole against C. difficile, versus vancomycin reduced recurrent disease by 53%, preserved microbiota diversity, increased secondary bile acids, did not increase resistome, but did not meet superiority in initial clinical response. Graphical Abstract https://tidbitapp.io/tidbits/test-7e5035e4-ad1b-417a-bee9-788b33377fe0
Language
English
Source (journal)
Clinical infectious diseases. - Chicago, Ill.
Publication
Cary : Oxford univ press inc , 2024
ISSN
1058-4838
DOI
10.1093/CID/CIAD792
Volume/pages
(2024) , p. 1-11
ISI
001155284900001
Pubmed ID
38305378
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
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Creation 04.03.2024
Last edited 08.03.2024
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