Dasiglucagon in Children with Congenital Hyperinsulinism up to 1 Year of Age: Results from a Randomized Clinical Trial.

IF 5 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Diva D De León, Indraneel Banerjee, Sebastian Kummer, Sune Birch, Eva Bøge, Jelena Ivkovic, David M Kendall, Paul S Thornton
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引用次数: 0

Abstract

Context: Congenital hyperinsulinism (CHI) is a cause of persistent hypoglycemia in childhood with considerable risk of lifelong neurological sequelae. Available pharmacological therapies are limited. Dasiglucagon is a glucagon analog for the treatment of hypoglycemia.

Objective: To assess efficacy and safety of dasiglucagon in children with CHI up to 1 year of age.

Methods: This study included a randomized, crossover, double-blind, placebo-controlled Part 1, and an open-label, single-arm Part 2 at four centers in Germany, UK, and USA. Participants comprised children with CHI aged 7 days to 12 months who were dependent on IV glucose. In Part 1, participants were randomized to dasiglucagon or placebo for 48 hours, then crossed over to the other treatment for 48 hours. In Part 2, all participants received dasiglucagon for 21 days. The primary outcome was mean IV glucose infusion rate (GIR) in the last 12 hours of Part 1.

Results: Between 6/19/2020 and 2/9/2022, 12 eligible participants were randomized to dasiglucagon-placebo (n = 7) or placebo-dasiglucagon (n = 5). The IV GIR was significantly reduced with dasiglucagon compared with placebo (least-squares mean 4.3 mg/kg/min [95% confidence interval [CI], 1.04 to 7.60 mg/kg/min] and 9.5 mg/kg/min [95% CI, 6.24 to 12.81 mg/kg/min], respectively; P = .004). The most frequent adverse events in both treatment groups were gastrointestinal, dermatological, and metabolism and nutritional disorders.

Conclusion: In infants with CHI, dasiglucagon significantly reduced the amount of IV glucose needed to maintain euglycemia compared with placebo. Dasiglucagon represents a promising treatment for the management of CHI.

达西胰高血糖素治疗 1 岁以下先天性胰岛素过多症患儿:随机临床试验的结果。
背景:先天性胰岛素分泌过多症(CHI)是导致儿童持续低血糖的原因之一,并有可能导致终身神经系统后遗症。现有的药物疗法非常有限。达西胰高血糖素是一种治疗低血糖症的胰高血糖素类似物:评估达西胰高血糖素对 1 岁以下 CHI 患儿的疗效和安全性:本研究包括随机、交叉、双盲、安慰剂对照的第一部分和开放标签、单臂对照的第二部分,分别在德国、英国和美国的四个中心进行。参试者包括年龄在 7 天至 12 个月之间、依赖静脉注射葡萄糖的 CHI 患儿。在第 1 部分中,参与者被随机分配到达西胰高血糖素或安慰剂治疗 48 小时,然后交叉到另一种治疗方法治疗 48 小时。在第二部分中,所有参与者接受达西胰高血糖素治疗 21 天。主要结果是第一部分最后12小时的平均静脉葡萄糖输注率(GIR):结果:在 2020 年 6 月 19 日至 2022 年 9 月 2 日期间,12 名符合条件的参与者随机接受了达西胰高血糖素-安慰剂(7 人)或安慰剂-达西胰高血糖素(5 人)治疗。与安慰剂相比,达西胰高血糖素的静脉注射 GIR 明显降低(最小二乘法平均值分别为 4.3 mg/kg/min[95% 置信区间 [CI],1.04 至 7.60 mg/kg/min]和 9.5 mg/kg/min[95% 置信区间 [CI],6.24 至 12.81 mg/kg/min];P = .004)。两组治疗中最常见的不良反应是胃肠道、皮肤以及代谢和营养紊乱:结论:与安慰剂相比,达西胰高血糖素可显著减少CHI婴儿维持优血糖所需的静脉注射葡萄糖量。达西胰高血糖素是一种很有前景的CHI治疗方法。
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来源期刊
Journal of Clinical Endocrinology & Metabolism
Journal of Clinical Endocrinology & Metabolism 医学-内分泌学与代谢
CiteScore
11.40
自引率
5.20%
发文量
673
审稿时长
1 months
期刊介绍: The Journal of Clinical Endocrinology & Metabolism is the world"s leading peer-reviewed journal for endocrine clinical research and cutting edge clinical practice reviews. Each issue provides the latest in-depth coverage of new developments enhancing our understanding, diagnosis and treatment of endocrine and metabolic disorders. Regular features of special interest to endocrine consultants include clinical trials, clinical reviews, clinical practice guidelines, case seminars, and controversies in clinical endocrinology, as well as original reports of the most important advances in patient-oriented endocrine and metabolic research. According to the latest Thomson Reuters Journal Citation Report, JCE&M articles were cited 64,185 times in 2008.
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