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Vehreschild MJGT, Ducher A, Louie T, et al. An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones. J Antimicrob Chemother. 2022;doi: 10.1093/jac/dkab474.
Vehreschild, M. J. G. T., Ducher, A., Louie, T., Cornely, O. A., Feger, C., Dane, A., Varastet, M., Vitry, F., de Gunzburg, J., Andremont, A., Mentré, F., & Wilcox, M. H. (2022). An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones. The Journal of antimicrobial chemotherapy, . https://doi.org/10.1093/jac/dkab474
Vehreschild, Maria J G T, et al. "An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones." The Journal of antimicrobial chemotherapy vol. (2022). doi: https://doi.org/10.1093/jac/dkab474
Vehreschild MJGT, Ducher A, Louie T, Cornely OA, Feger C, Dane A, Varastet M, Vitry F, de Gunzburg J, Andremont A, Mentré F, Wilcox MH. An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones. J Antimicrob Chemother. 2022 Jan 07; doi: 10.1093/jac/dkab474. Epub 2022 Jan 07. PMID: 35016205.
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J Antimicrob Chemother. 2022 Jan 07; doi: 10.1093/jac/dkab474. Epub 2022 Jan 07.

An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones.

The Journal of antimicrobial chemotherapy

Maria J G T Vehreschild, Annie Ducher, Thomas Louie, Oliver A Cornely, Celine Feger, Aaron Dane, Marina Varastet, Fabien Vitry, Jean de Gunzburg, Antoine Andremont, France Mentré, Mark H Wilcox

Affiliations

  1. Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
  2. Da Volterra, Paris, France.
  3. Cumming School of Medicine, University of Calgary, Calgary, Canada.
  4. Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University of Cologne, Cologne, Germany.
  5. Faculty of Medicine and University Hospital Cologne, Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
  6. Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), University of Cologne, Cologne, Germany.
  7. German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
  8. EMIBiotech, Paris, France.
  9. Danestat, Macclesfield, UK.
  10. Université de Paris, IAME, INSERM U1137, Paris, France.
  11. Leeds Institute of Medical Research, University of Leeds and Leeds Teaching Hospitals, Leeds, UK.

PMID: 35016205 DOI: 10.1093/jac/dkab474

Abstract

BACKGROUND: DAV132 (colon-targeted adsorbent) has prevented antibiotic-induced effects on microbiota in healthy volunteers.

OBJECTIVES: To assess DAV132 safety and biological efficacy in patients.

PATIENTS AND METHODS: An open-label, randomized [stratification: fluoroquinolone (FQ) indication] multicentre trial comparing DAV132 (7.5 g, 3 times a day, orally) with No-DAV132 in hospitalized patients requiring 5-21 day treatment with FQs and at risk of Clostridioides difficile infection (CDI). FQ and DAV132 were started simultaneously, DAV132 was administered for 48 h more, and patients were followed up for 51 days. The primary endpoint was the rate of adverse events (AEs) independently adjudicated as related to DAV132 and/or FQ. The planned sample size of 260 patients would provide a 95% CI of ±11.4%, assuming a 33% treatment-related AE rate. Plasma and faecal FQ concentrations, intestinal microbiota diversity, intestinal colonization with C. difficile, MDR bacteria and yeasts, and ex vivo resistance to C. difficile faecal colonization were assessed.

RESULTS: Two hundred and forty-three patients (median age 71 years; 96% with chronic comorbidity) were included (No-DAV132, n = 120; DAV132, n = 123). DAV132- and/or FQ-related AEs did not differ significantly: 18 (14.8%) versus 13 (10.8%) in DAV132 versus No-DAV132 patients (difference 3.9%; 95% CI: -4.7 to 12.6). Day 4 FQ plasma levels were unaffected. DAV132 was associated with a >98% reduction in faecal FQ levels (Day 4 to end of treatment; P < 0.001), less impaired microbiota diversity (Shannon index; P = 0.003), increased ex vivo resistance to C. difficile colonization (P = 0.0003) and less frequent FQ-induced VRE acquisition (P = 0.01).

CONCLUSIONS: In FQ-treated hospitalized patients, DAV132 was well tolerated, and FQ plasma concentrations unaffected. DAV132 preserved intestinal microbiota diversity and C. difficile colonization resistance.

© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

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