Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion

University of Calgary

Overview

This study will provide feasibility data regarding the conduct of a clinical trail evaluating the use of early aggressive inpatient intravenous rehydration in children with Shiga Toxin producing E. coli infection.

Background: Shiga toxin-producing Escherichia coli (STEC) cause a spectrum of disease, ranging from asymptomatic carriage to bloody diarrhea and the hemolytic uremic syndrome (HUS). HUS is caused by a toxin that destroys red blood cells, consumes platelets and impairs kidney function. HUS results in morbidity and even death in otherwise healthy children. Over the last 30 years however, there has been extremely limited progress in preventing acute and long-term complications in children with STEC infection. However, it is believed that Shiga toxins generate clots or blockages in the kidneys that damage it much the way strokes cause brain damage. There is emerging evidence that if children with STEC infection are recognized early, then the interval between diarrhea onset and the presence of HUS could be exploited to preserve kidney function through the use of intravenous rehydration. Study Design: The investigators propose to conduct the first randomized clinical trial of volume expansion therapy in children with STEC infection. Employing Alberta's unique province-wide microbiology network and its only two pediatric tertiary care centres, the investigators will conduct a proof of principal feasibility study that evaluates novel technologies to identify STEC infected children and those at risk for HUS. Objectives: The primary outcome will be process: number of children recruited. Secondary outcomes will include: 1) resources: retention; refusal; compliance; eligibility criteria; questionnaires; data collection tools; and time requirements; 2) management: capacity and impact on clinical services; 3) scientific: utility of point-of-care STEC diagnostics; use of urine biomarkers to identify high risk children, monitoring of kidney injury and response to therapy; and safety. Significance: This pilot will provide the necessary data to integrate novel technologies into the design and conduct of a multicentre, multinational, clinical trial that will reduce morbidity and mortality from STEC infection.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Conditions

Hemolytic-Uremic Syndrome

Interventions

D5-0.9%NSDRUG

Admission for intravascular volume expansion

Routine home oral rehydrationDRUG

Routine oral fluids as is given at home to all children with acute diarrheal disease

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age \<18.0 years; 2. STEC infection \[positive culture OR antigen OR polymerase chain reaction test for Stx/gene\]; 3. Day of illness 1-10: Children who develop HUS will do so by day #14 of illness;8 restricting enrolment to the first 10 days will ensure all participants are at risk of HUS. Exclusion Criteria: 1. Evidence of evolving HUS: A) Hematocrit \<30% OR B) Platelet count \<150 x 109/L; 2. Responsible physician desires patient admission (therefore unable to randomize); 3. Unable to contact family within 48 hours of positive stool test; 4. Patient with history of atypical HUS; 5. Chronic disease limiting fluid volumes administered (e.g. impaired cardiac function)

Locations (1)

Alberta Children's Hospital

Calgary, Alberta, Canada

Outcomes

Primary Outcomes

Number of children enrolled in the study protocol

The number of children recruited per month per site will be calculated and will be related to the number screened, number eligible, and number consented.