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.