Outcomes from a 12-Week, Open-Label, Multicenter Clinical Trial of Teduglutide in Pediatric Short Bowel Syndrome

详细信息    查看全文

• 作者：Beth A. Carter ; MD¹ ; ^bac@bcm.edu ; Valeria C. Cohran ; MD ; MS² ; Conrad R. Cole ; MD ; MPH ; MSc³ ; Mark R. Corkins ; MD⁴ ; Reed A. Dimmitt ; MD ; MSPH⁵ ; Christopher Duggan ; MD ; MPH⁶ ; Susan Hill ; MRCPCH ; DM⁷ ; Simon Horslen ; MB ; ChB ; FRCPCH⁸ ; Joel D. Lim ; MD⁹ ; David F. Mercer ; MD ; PhD ; FRCS(C)¹⁰ ; Russell J. Merritt ; MD ; PhD¹¹ ; Peter F. Nichol ; MD ; PhD¹² ; Luther Sigurdsson ; MD¹³ ; Daniel H. Teitelbaum ; MD¹⁴ ; ^* ; John Thompson ; MD¹⁵ ; Charles Vanderpool ; MD¹⁶ ; Juliana F. Vaughan ; MD¹⁷ ; Benjamin Li ; MS¹⁸ ; ^&dagger ; ; Nader N. Youssef ; MD¹⁹ ; ^&Dagger ; ; Robert S. Venick ; MD²⁰ ; Samuel A. Kocoshis ; MD³
• 关键词：glucagon-like peptide 2 ; intestinal failure ; pediatric short bowel syndrome ; short gut syndrome
• 刊名：The Journal of Pediatrics
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：181
• 期：Complete
• 页码：102-111.e5
• 全文大小：553 K
• 卷排序：181

文摘

To determine safety and pharmacodynamics/efficacy of teduglutide in children with intestinal failure associated with short bowel syndrome (SBS-IF).Study designThis 12-week, open-label study enrolled patients aged 1-17 years with SBS-IF who required parenteral nutrition (PN) and showed minimal or no advance in enteral nutrition (EN) feeds. Patients enrolled sequentially into 3 teduglutide cohorts (0.0125 mg/kg/d [n = 8], 0.025 mg/kg/d [n = 14], 0.05 mg/kg/d [n = 15]) or received standard of care (SOC, n = 5). Descriptive summary statistics were used.ResultsAll patients experienced ≥1 treatment-emergent adverse event; most were mild or moderate. No serious teduglutide-related treatment-emergent adverse events occurred. Between baseline and week 12, prescribed PN volume and calories (kcal/kg/d) changed by a median of −41% and −45%, respectively, with 0.025 mg/kg/d teduglutide and by −25% and −52% with 0.05 mg/kg/d teduglutide. In contrast, PN volume and calories changed by 0% and −6%, respectively, with 0.0125 mg/kg/d teduglutide and by 0% and −1% with SOC. Per patient diary data, EN volume increased by a median of 22%, 32%, and 40% in the 0.0125, 0.025, and 0.05 mg/kg/d cohorts, respectively, and by 11% with SOC. Four patients achieved independence from PN, 3 in the 0.05 mg/kg/d cohort and 1 in the 0.025 mg/kg/d cohort. Study limitations included its short-term, open-label design, and small sample size.ConclusionsTeduglutide was well tolerated in pediatric patients with SBS-IF. Teduglutide 0.025 or 0.05 mg/kg/d was associated with trends toward reductions in PN requirements and advancements in EN feeding in children with SBS-IF.Trial registrationClinicalTrials.gov:NCT01952080; EudraCT: 2013-004588-30.