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Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)

BACKGROUND: Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial...

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Autores principales: Wolf, Joshua, Kalocsai, Krisztina, Fortuny, Claudia, Lazar, Stefan, Bosis, Samantha, Korczowski, Bartosz, Petit, Arnaud, Bradford, Daniel, Croos-Dabrera, Rodney, Incera, Elodie, Melis, Joost, van Maanen, Rob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744996/
https://www.ncbi.nlm.nih.gov/pubmed/31773143
http://dx.doi.org/10.1093/cid/ciz1149
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author Wolf, Joshua
Kalocsai, Krisztina
Fortuny, Claudia
Lazar, Stefan
Bosis, Samantha
Korczowski, Bartosz
Petit, Arnaud
Bradford, Daniel
Croos-Dabrera, Rodney
Incera, Elodie
Melis, Joost
van Maanen, Rob
author_facet Wolf, Joshua
Kalocsai, Krisztina
Fortuny, Claudia
Lazar, Stefan
Bosis, Samantha
Korczowski, Bartosz
Petit, Arnaud
Bradford, Daniel
Croos-Dabrera, Rodney
Incera, Elodie
Melis, Joost
van Maanen, Rob
author_sort Wolf, Joshua
collection PubMed
description BACKGROUND: Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. METHODS: Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. RESULTS: Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. CONCLUSIONS: Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. CLINICAL TRIALS REGISTRATION: NCT02218372
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spelling pubmed-77449962020-12-22 Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE) Wolf, Joshua Kalocsai, Krisztina Fortuny, Claudia Lazar, Stefan Bosis, Samantha Korczowski, Bartosz Petit, Arnaud Bradford, Daniel Croos-Dabrera, Rodney Incera, Elodie Melis, Joost van Maanen, Rob Clin Infect Dis Major Articles and Commentaries BACKGROUND: Fidaxomicin, a narrow-spectrum antibiotic approved for Clostridioides (Clostridium) difficile infection (CDI) in adults, is associated with lower rates of recurrence than vancomycin; however, pediatric data are limited. This multicenter, investigator-blind, phase 3, parallel-group trial assessed the safety and efficacy of fidaxomicin in children. METHODS: Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, 4 times daily). Safety assessments included treatment-emergent adverse events. The primary efficacy end point was confirmed clinical response (CCR), 2 days after the end of treatment (EOT). Secondary end points included global cure (GC; CCR without CDI recurrence) 30 days after EOT (end of study; EOS). Plasma and stool concentrations of fidaxomicin and its active metabolite OP-1118 were measured. RESULTS: Of 148 patients randomized, 142 were treated (30 <2 years old). The proportion of participants with treatment-emergent adverse events was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of 3 deaths in the fidaxomicin arm during the study, none were CDI or treatment related. The rate of CCR at 2 days after EOT was 77.6% (76 of 98 patients) with fidaxomicin and 70.5% (31 of 44) with vancomycin, whereas the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% vs 50.0%; adjusted treatment difference, 18.8%; 95% confidence interval, 1.5%–35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal, and stool concentrations were high. CONCLUSIONS: Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI. CLINICAL TRIALS REGISTRATION: NCT02218372 Oxford University Press 2019-11-27 /pmc/articles/PMC7744996/ /pubmed/31773143 http://dx.doi.org/10.1093/cid/ciz1149 Text en © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Articles and Commentaries
Wolf, Joshua
Kalocsai, Krisztina
Fortuny, Claudia
Lazar, Stefan
Bosis, Samantha
Korczowski, Bartosz
Petit, Arnaud
Bradford, Daniel
Croos-Dabrera, Rodney
Incera, Elodie
Melis, Joost
van Maanen, Rob
Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title_full Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title_fullStr Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title_full_unstemmed Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title_short Safety and Efficacy of Fidaxomicin and Vancomycin in Children and Adolescents with Clostridioides (Clostridium) difficile Infection: A Phase 3, Multicenter, Randomized, Single-blind Clinical Trial (SUNSHINE)
title_sort safety and efficacy of fidaxomicin and vancomycin in children and adolescents with clostridioides (clostridium) difficile infection: a phase 3, multicenter, randomized, single-blind clinical trial (sunshine)
topic Major Articles and Commentaries
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744996/
https://www.ncbi.nlm.nih.gov/pubmed/31773143
http://dx.doi.org/10.1093/cid/ciz1149
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