Dataset Information

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).

ABSTRACT: 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 safety and efficacy of fidaxomicin in children. METHODS:Patients aged <18 years with confirmed CDI were randomized 2:1 to ten days of treatment with fidaxomicin (suspension or tablets, twice daily) or vancomycin (suspension or tablets, four times daily). Safety assessments included treatment-emergent adverse events (TEAEs). The primary efficacy endpoint was confirmed clinical response (CCR), 2 days after end of treatment (EOT). Secondary endpoints 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 TEAEs was similar with fidaxomicin (73.5%) and vancomycin (75.0%). Of three 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% (76/98) with fidaxomicin and 70.5% (31/44) with vancomycin, while the rate of GC at EOS was significantly higher in participants receiving fidaxomicin (68.4% versus 50.0%; adjusted treatment difference 18.8%; 95% CI 1.5%, 35.3%). Systemic absorption of fidaxomicin and OP-1118 was minimal and stool concentrations were high. CONCLUSIONS:Fidaxomicin was well tolerated and demonstrated significantly higher rates of GC, compared with vancomycin, in children and adolescents with CDI.

SUBMITTER: Wolf J

PROVIDER: S-EPMC7744996 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

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 J Kalocsai Krisztina K Fortuny Claudia C Lazar Stefan S Bosis Samantha S Korczowski Bartosz B Petit Arnaud A Bradford Daniel D Croos-Dabrera Rodney R Incera Elodie E Melis Joost J van Maanen Rob R

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20201201 10

<h4>Background</h4>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.<h4>Methods</h4>Patients aged <18 years with confirmed CDI were randomized 2:1 to 10 days of treatment with fidaxomicin (suspension o ...[more]

PMID: 31773143

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Project description:Our study sought to compare the strain types of Clostridium difficile causing initial and recurrent episodes of C. difficile infection (CDI) in adult patients with a first episode of CDI or 1 prior episode of CDI within the previous 90 days. Strains originated from patients who had been entered into two phase 3 randomized clinical trials of fidaxomicin versus vancomycin. Isolates of C. difficile from the initial and recurrent episodes within 28 (± 2) days of cure of CDI were compared using restriction endonuclease analysis (REA) typing. Paired isolates were available from 90 of 194 (46%) patients with recurrent CDI. Patients with isolates available were significantly younger (P = .008) and more likely to be from Canadian sites (P = .0001), compared with patients without isolates. In 75 of 90 subjects (83.3%), the identical REA type strain was identified at recurrence and the initial episode (putative relapse). Early recurrences (0-14 days after treatment completion) were relapses in 86.7% and a new strain (reinfection) in 13.3%. Later recurrences (15-31 days after treatment) were relapses in 76.7% and reinfections in 23.3%. Mean time (± standard deviation) to recurrence was 12.2 (± 6.4) days for relapses and 14.7 (± 6.8) days for reinfections (P = .177). The most common BI/NAP1/027 group and the previous US epidemic REA group J/NAP2/001 had a significantly higher combined rate of recurrence with the same strain (relapse), compared with the other REA groups (39 of 42 [93%] vs 36 of 48 [75%], respectively; P = .023). We found a higher than historic rate of recurrent CDI caused by the same isolate as the original episode, a finding that may be related to the relatively short observation period in this study and the high frequency of isolation of epidemic strains, such as groups BI and J, for which relapse rates may be higher than for other REA groups. Caution in generalizing these observations is required, because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates.

Dataset Information

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).

Publications

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).

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