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LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study
BACKGROUND: Clostridium difficile infection (CDI), a common cause of antibiotic-associated diarrhea, leads to substantial healthcare burden. In children and young adults, the incidence of CDI is increasing. Fidaxomicin (FDX) is a narrow-spectrum macrocyclic antibiotic treatment for CDI in adults, bu...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253862/ http://dx.doi.org/10.1093/ofid/ofy229.2186 |
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author | Wolf, Joshua Kalocsai, Krisztina Fortuny, Claudia Lazar, Stefan Bosis, Samantha Korczowski, Bartosz Petit, Arnaud Bradford, Daniel 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 Incera, Elodie Melis, Joost Van Maanen, Rob |
author_sort | Wolf, Joshua |
collection | PubMed |
description | BACKGROUND: Clostridium difficile infection (CDI), a common cause of antibiotic-associated diarrhea, leads to substantial healthcare burden. In children and young adults, the incidence of CDI is increasing. Fidaxomicin (FDX) is a narrow-spectrum macrocyclic antibiotic treatment for CDI in adults, but pediatric data are limited. The primary objective of our study was to investigate safety and efficacy of FDX and vancomycin (VAN) in children. METHODS: Patients aged <18 years with new laboratory-confirmed CDI and diarrhea (watery diarrhea for patients aged <2 years, and ≥3 unformed bowel movements in 24 hours for patients aged ≥2 years) were enrolled in a randomized, investigator-blinded study. Participants were randomized (2:1) to 10 days of treatment with either FDX (oral suspension 32 mg/kg/day or tablets 200 mg BID) or VAN (oral liquid 40 mg/kg/day or capsules 125 mg QID). Concurrent use of other antibiotic treatment for CDI was not permitted. Randomization was stratified by age group. The primary efficacy endpoint was confirmed clinical response (CCR) at Day 12 (absence of diarrhea for 2 consecutive days on treatment and remaining well until treatment discontinuation). Other efficacy endpoints were also evaluated. RESULTS: Of 142 patients in the full analysis set (FDX n = 98; VAN n = 44), 30 were aged <2 years, 48 were aged 2 to <6 years, 36 were aged 6 to <12 years and 28 were aged 12 to <18 years. At baseline, 28.6% of the FDX arm and 22.7% of the VAN arm had prior confirmed CDI. Overall, 73.5% of the FDX arm and 75.0% of the VAN arm had ≥1 treatment-emergent adverse event. There were three deaths in the FDX arm during the study and two deaths in the VAN arm after end of study (post-Day 40); none were related to treatment. There was a trend to improved CCR and other efficacy outcomes for FDX (figure) and this was statistically significant for global cure (adjusted difference 18.8%; 95% CI 1.5%, 35.3%). CONCLUSIONS: There was a consistent trend for improved efficacy outcomes with FDX compared with VAN, as shown by the adjusted treatment differences, although the small sample size precluded conclusions on most outcome differences. Figure. [Image: see text] DISCLOSURES: J. Wolf, Astellas Pharma: Consultant and Non-Financial Support, Consulting fee and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . K. Kalocsai, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . C. Fortuny, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . S. Lazar, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . S. Bosis, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . B. Korczowski, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . A. Petit, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . D. Bradford, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. E. Incera, Astellas Pharma: Employee of Iqvia, a CRO contracted by Astellas, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . J. Melis, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. R. Van Maanen, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. |
format | Online Article Text |
id | pubmed-6253862 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62538622018-11-28 LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study Wolf, Joshua Kalocsai, Krisztina Fortuny, Claudia Lazar, Stefan Bosis, Samantha Korczowski, Bartosz Petit, Arnaud Bradford, Daniel Incera, Elodie Melis, Joost Van Maanen, Rob Open Forum Infect Dis Abstracts BACKGROUND: Clostridium difficile infection (CDI), a common cause of antibiotic-associated diarrhea, leads to substantial healthcare burden. In children and young adults, the incidence of CDI is increasing. Fidaxomicin (FDX) is a narrow-spectrum macrocyclic antibiotic treatment for CDI in adults, but pediatric data are limited. The primary objective of our study was to investigate safety and efficacy of FDX and vancomycin (VAN) in children. METHODS: Patients aged <18 years with new laboratory-confirmed CDI and diarrhea (watery diarrhea for patients aged <2 years, and ≥3 unformed bowel movements in 24 hours for patients aged ≥2 years) were enrolled in a randomized, investigator-blinded study. Participants were randomized (2:1) to 10 days of treatment with either FDX (oral suspension 32 mg/kg/day or tablets 200 mg BID) or VAN (oral liquid 40 mg/kg/day or capsules 125 mg QID). Concurrent use of other antibiotic treatment for CDI was not permitted. Randomization was stratified by age group. The primary efficacy endpoint was confirmed clinical response (CCR) at Day 12 (absence of diarrhea for 2 consecutive days on treatment and remaining well until treatment discontinuation). Other efficacy endpoints were also evaluated. RESULTS: Of 142 patients in the full analysis set (FDX n = 98; VAN n = 44), 30 were aged <2 years, 48 were aged 2 to <6 years, 36 were aged 6 to <12 years and 28 were aged 12 to <18 years. At baseline, 28.6% of the FDX arm and 22.7% of the VAN arm had prior confirmed CDI. Overall, 73.5% of the FDX arm and 75.0% of the VAN arm had ≥1 treatment-emergent adverse event. There were three deaths in the FDX arm during the study and two deaths in the VAN arm after end of study (post-Day 40); none were related to treatment. There was a trend to improved CCR and other efficacy outcomes for FDX (figure) and this was statistically significant for global cure (adjusted difference 18.8%; 95% CI 1.5%, 35.3%). CONCLUSIONS: There was a consistent trend for improved efficacy outcomes with FDX compared with VAN, as shown by the adjusted treatment differences, although the small sample size precluded conclusions on most outcome differences. Figure. [Image: see text] DISCLOSURES: J. Wolf, Astellas Pharma: Consultant and Non-Financial Support, Consulting fee and This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . K. Kalocsai, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . C. Fortuny, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . S. Lazar, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . S. Bosis, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . B. Korczowski, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . A. Petit, Astellas Pharma: Non-Financial Support, This study was initiated and sponsored by Astellas. Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . D. Bradford, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. E. Incera, Astellas Pharma: Employee of Iqvia, a CRO contracted by Astellas, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. . J. Melis, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. R. Van Maanen, Astellas Pharma: Employee and Non-Financial Support, Medical writing support was provided by Cello Health MedErgy and funded by Astellas. and Salary. Oxford University Press 2018-11-26 /pmc/articles/PMC6253862/ http://dx.doi.org/10.1093/ofid/ofy229.2186 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of 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 | Abstracts Wolf, Joshua Kalocsai, Krisztina Fortuny, Claudia Lazar, Stefan Bosis, Samantha Korczowski, Bartosz Petit, Arnaud Bradford, Daniel Incera, Elodie Melis, Joost Van Maanen, Rob LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title | LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title_full | LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title_fullStr | LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title_full_unstemmed | LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title_short | LB12. Safety and Efficacy of Fidaxomicin and Vancomycin in Pediatric Patients with Clostridium difficile Infection: Phase III, Multicenter, Investigator-blind, Randomized, Parallel Group (SUNSHINE) Study |
title_sort | lb12. safety and efficacy of fidaxomicin and vancomycin in pediatric patients with clostridium difficile infection: phase iii, multicenter, investigator-blind, randomized, parallel group (sunshine) study |
topic | Abstracts |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6253862/ http://dx.doi.org/10.1093/ofid/ofy229.2186 |
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