Clinical trial NCT03275792: Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion
Official title: Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Hemolytic-Uremic Syndrome
Keywords: Shiga-Toxigenic Escherichia coli
Child
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2017-09-08
Enrollment: 0
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Number of children enrolled in the study protocol
timeFrame: at the end of the 24 month study recruiting period
Secondary outcomes:
measure: The proportion of children enrolled in each study arm who develop adverse events
timeFrame: at the end of the 24 month study recruiting period
measure: Retention
timeFrame: at the end of the 24 month study recruiting period
measure: Time requirements
timeFrame: at the end of the 24 month study recruiting period
measure: Child/family perspectives
timeFrame: at the end of the 24 month study recruiting period
measure: compliance/adherence
timeFrame: at the end of the 24 month study recruiting period
measure: data collection tool performance
timeFrame: at the end of the 24 month study recruiting period
measure: Impact on clinical services
timeFrame: at the end of the 24 month study recruiting period
measure: Cost
timeFrame: at the end of the 24 month study recruiting period
Other outcomes:
measure: Point-of-Care STEC diagnosis
timeFrame: at the end of the 24 month study recruiting period
measure: Urine biomarkers
timeFrame: at the end of the 24 month study recruiting period
measure: Point-of-Care STEC diagnosis
timeFrame: at the end of the 24 month study recruiting period
measure: Point-of-Care STEC diagnosis
timeFrame: at the end of the 24 month study recruiting period
Locations:
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
Study officials:
affiliation: University of Calgary
name: Stephen Freedman, MDCM, MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Imdad A, Mackoff SP, Urciuoli DM, Syed T, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2021 Jul 5;7(7):CD012997. doi: 10.1002/14651858.CD012997.pub2.