Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial)

Trials

Study Protocol

Stuart L. Goldstein¹  T. Charles Casper²  Kadyn Kimball²  Melissa Metheney²  Myka Estes³  David Schnadower⁴  Phillip I. Tarr⁵  Andrew T. Pavia⁶  Benjamin S. Wilfond⁷  Silviu Grisaru⁸  Stephen B. Freedman⁹ 

[1] Center for Acute Care Nephrology, Cincinnati Children, s Hospital Medical Center and Department of Pediatrics University of Cincinnati College of Medicine, Cincinnati, OH, USA;Department of Pediatrics, University of Utah, Salt Lake City, UT, USA;Departments of Pediatrics and Emergency Medicine, Alberta Children’s Hospital, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Division of Emergency Medicine, Cincinnati Children, s Hospital Medical Center and Department of Pediatrics University of Cincinnati College of Medicine, Cincinnati, OH, USA;Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, MO, USA;Division of Pediatric Infectious Diseases, Department of Pediatrics and Internal Medicine, University of Utah, Salt Lake City, UT, USA;Divisions of Bioethics and Palliative Care and Pulmonary and Sleep Medicine, Department of Pediatrics and Department of Bioethics and Humanities, University of Washington School of Medicine, Seattle, WA, USA;Section of Nephrology, Department of Pediatrics, Alberta Children, s Hospital, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;Sections of Pediatric Emergency Medicine and Gastroenterology, Departments of Pediatrics and Emergency Medicine, Alberta Childrens Hospital, Alberta Childrens Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada;

关键词: Shiga toxin-producing E. coli (STEC);    Hemolytic uremic syndrome (HUS);    Hyperhydration;    Euvolemia;    Children;    Gastroenteritis;    Bloody diarrhea;    Emergency department;    Acute kidney injury;    Hospitalization;   

DOI  :  10.1186/s13063-023-07379-w

 received in 2023-03-17, accepted in 2023-05-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundShiga 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.MethodsWe 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.DiscussionHUS 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.Trial registrationClinicalTrials.gov NCT05219110. Registered on February 1, 2022.

【 授权许可】

CC BY   
© The Author(s) 2023

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