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

Abstract

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.

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.