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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.
Okhuysen, Pablo C; Ramesh, Mayur S; Louie, Thomas; Kiknadze, Nino; Torre-Cisneros, Julian; de Oliveira, Claudia Murta; Van Steenkiste, Christophe; Stychneuskaya, Alena; Garey, Kevin W; Garcia-Diaz, Julia; Li, Jianling; Duperchy, Esther; Chang, Betty Y; Sukbuntherng, Juthamas; Montoya, Jose G; Styles, Lori; Clow, Fong; James, Danelle; Dubberke, Erik R; Wilcox, Mark.
Afiliación
  • Okhuysen PC; Department of Infectious Diseases, Infection Control, and Employee Heatlh, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
  • Ramesh MS; Henry Ford Health, Detroit, Michigan, USA.
  • Louie T; Foothills Medical Center and University of Calgary, Calgary, Canada.
  • Kiknadze N; Aversi Clinic, Tbilisi, Georgia.
  • Torre-Cisneros J; Reina Sofia University Hospital-IMIBIC, University of Córdoba, CIBERINFEC, Cordoba, Spain.
  • de Oliveira CM; Santa Casa de Belo Horizonte, Belo Horizonte, Brazil.
  • Van Steenkiste C; Algemeen Ziekenhuis Maria Middelares, Ghent, Belgium.
  • Stychneuskaya A; University Antwerp,Antwerp, Belgium.
  • Garey KW; Vitebsk Regional Clinical Hospital of Infectious Diseases, Vitebsk, Belarus.
  • Garcia-Diaz J; University of Houston College of Pharmacy, Houston, Texas, USA.
  • Li J; Ochsner Health, New Orleans, Louisiana, USA.
  • Duperchy E; Summit Therapeutics, Menlo Park, California, USA.
  • Chang BY; Summit Therapeutics, Menlo Park, California, USA.
  • Sukbuntherng J; Summit Therapeutics, Menlo Park, California, USA.
  • Montoya JG; Summit Therapeutics, Menlo Park, California, USA.
  • Styles L; Summit Therapeutics, Menlo Park, California, USA.
  • Clow F; Dr. Jack S. Remington Laboratory for Specialty Diagnostics, Palo Alto Medical Foundation, Palo Alto, California, USA.
  • James D; Summit Therapeutics, Menlo Park, California, USA.
  • Dubberke ER; Summit Therapeutics, Menlo Park, California, USA.
  • Wilcox M; Summit Therapeutics, Menlo Park, California, USA.
Clin Infect Dis ; 78(6): 1462-1472, 2024 Jun 14.
Article en En | MEDLINE | ID: mdl-38305378
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 (∼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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Clostridioides difficile / Infecciones por Clostridium / Microbioma Gastrointestinal / Antibacterianos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vancomicina / Clostridioides difficile / Infecciones por Clostridium / Microbioma Gastrointestinal / Antibacterianos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Infect Dis Asunto de la revista: DOENCAS TRANSMISSIVEIS Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos