背景:产志贺毒素的大肠杆菌(STEC)感染影响全球儿童和成人,治疗仍然完全是支持性的。多达15-20%的儿童感染了高危STEC(即,产生志贺毒素的大肠杆菌2)发展为溶血性贫血,血小板减少症,和肾衰竭(即,溶血性尿毒综合征(HUS),超过一半的人需要急性透析,3%的人死亡。尽管没有一种疗法被广泛接受为能够预防HUS及其并发症的发展,多项观察性研究表明,血管内容量扩张(过度水合)可预防终末器官损伤.需要一项随机试验来证实或反驳这一假设。
方法:我们将进行务实,嵌入式,集群随机化,在26个儿科机构进行交叉试验,以确定是否过度水合,与保守的液体管理相比,改善1040例STEC高危感染儿童的结局.主要结果是30天内的主要不良肾脏事件(MAKE30),包括死亡在内的综合措施,开始新的肾脏替代疗法,或持续性肾功能不全.次要结果包括危及生命,肾外并发症,HUS的发展。路径符合条件的儿童将根据每个路径的机构分配进行治疗。在过度水合途径中,所有符合条件的儿童均住院治疗,并给予200%的维持平衡晶体液,直至目标体重增加10%,血细胞比容降低20%.保守性液体管理路径中的站点将儿童作为住院或门诊患者进行管理,根据临床医生的偏好,路径集中在密切的实验室监测,和维持血容量正常。根据历史数据,我们估计,在我们的保守液体管理途径中,10%的儿童将经历主要结局.26个集群平均招募40名患者,每个患者的组内相关系数为0.11,我们将有90%的能力来检测5%的绝对风险降低。
结论:HUS是一种没有治疗选择的毁灭性疾病。这项务实的研究将确定在高危STEC感染的儿童中,高水合是否可以降低与HUS相关的发病率。
背景:ClinicalTrials.govNCT05219110。2022年2月1日注册
BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (
hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis.
METHODS: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if
hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the
hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction.
CONCLUSIONS: HUS is a devastating illness with no treatment options. This pragmatic study will determine if
hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection.
BACKGROUND: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022.