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)
Por:
Wolf J, Kalocsai K, Fortuny-Guasch C, Lazar S, Bosis S, Korczowski B, Petit A, Bradford D, Croos-Dabrera R, Incera E, Melis J and van Maanen R
Publicada:
15 nov 2020
Resumen:
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 LOT 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.
Condusions. Compared with vancomycin, fidaxomicin was well tolerated and demonstrated significantly higher rates of GC in children and adolescents with CDI.
Filiaciones:
Wolf J:
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
Kalocsai K:
Gyermekinfektológia, Dél-pesti Centrumkórház Országos Haematológiai és Infektológiai Intézet, Budapest, Hungary
Fortuny-Guasch C:
Department of Paediatric Infectious Diseases, Hospital Sant Joan de Deu, Universitat de Barcelona, Barcelona, Spain
Lazar S:
Department of Pediatrics, Clinical Hospital for Infectious and Tropical Diseases "Dr. Victor Babe?", Bucharest, Romania
Bosis S:
Pediatric Highly Intensive Care Unit, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Korczowski B:
Department of Pediatrics and Pediatric Gastroenterology, University of Rzeszów, Rzeszów, Poland
Petit A:
Department of Pediatric Hematology and Oncology, Hôpital Trousseau, HUEP, APHP, Paris, France
Faculty of Medicine, Sorbonne Université, UMRS, GRC MyPAC, Paris, France
Bradford D:
Astellas Pharma B.V., Leiden, The Netherlands
Croos-Dabrera R:
Astellas Pharma Development, Northbrook, Illinois, USA
Incera E:
Astellas Pharma B.V., Leiden, The Netherlands
Melis J:
Astellas Pharma B.V., Leiden, The Netherlands
van Maanen R:
Astellas Pharma B.V., Leiden, The Netherlands
Green Submitted, Bronze
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