Volume Expansion in Children with Shiga Toxin-Producing E. coli Infection to Prevent or Mitigate Hemolytic Uremic Syndrome: Planning a Multinational Randomized Clinical Trial - Project Summary/Abstract
Long-term Objectives: To prevent or mitigate the complications of the hemolytic
uremic syndrome in children with Shiga Toxin-producing Escherichia coli (STEC)
infections.
Health-Relatedness of the Project: This study’s goals align with the NIAID’s
mission to conduct and support applied research to better treat and prevent
infectious diseases. The focus aligns with NIAID’s enteric diseases interest that
includes STEC infection. The latter are a priority because of their frequency (265,000
STEC infections annually in the US) and severity as over 35% of these infections are
caused by E. coli O157:H7 and 15% of infected children develop the HUS.
Specific Aims
Despite the conduct of numerous elegant molecular, cellular, and genomic research
studies, no safe and effective interventions that reduce the likelihood of severe renal
injury after STEC infections have been developed. Recent cohort studies, including
several led by our group, suggest that aggressive intravenous volume expansion
early in STEC infections could be nephroprotective. However, most North American
clinicians continue to rely on reactive care in cases of STEC infection, namely,
treating renal and hematologic consequences of STEC injury if and when they occur.
Our goal is to conduct a multicenter randomized clinical trial (RCT) to assess the
efficacy of intravascular volume expansion in STEC-infected children. In preparation
for such trial, the following specific aims are proposed: 1) Finalize the protocol,
statistical analysis plan and standard operating procedures to conduct a
rigorous, safe, reproducible and generalizable multinational RCT of
intravascular fluid expansion in STEC infected children; and 2) To pre-
emptively address implementation, feasibility, training, recruitment, financial
and ethical issues thereby ensuring the seamless, efficient, safe and
successful conduct of the trial.
