Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion

NCT ID: NCT03275792

Last Updated: 2020-11-09

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-31
• Study Completion Date: 2021-04-30

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.

Conditions

Hemolytic-Uremic Syndrome

Keywords

Shiga-Toxigenic Escherichia coli; Child

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Admission/Intravascular Volume Expansion

1. Infusion of 40 mL/kg of 0.9% normal saline (NS) IV over 60 minutes

2. 0.9% NS with 5% dextrose at 150% of standard maintenance volume

3. If urine output is <0.5 ml/kg/hr over a 12-hour period (AKI Stage 2), repeat 20 mL/kg bolus or boluses of 0.9% NS will be infused as long as there are no signs of central volume overload

4. Oral fluids ad lib along with strict input/output documentation

5. Fluids will be restricted if: A) Anuria for 12 hours OR B) Evidence of fluid overload

6. Daily laboratory tests and in-person assessment until inpatient discharge criteria reached:

A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child

7. Repeat hematocrit, platelet, renal function 24 and 72-hours post-discharge.

Group Type: EXPERIMENTAL

D5-0.9%NS

Intervention Type: DRUG

Admission for intravascular volume expansion

Outpatient Observation

1. Following standard emergency department (ED) care [volume status assessed; dehydration corrected employing oral rehydration in children with mild to moderate dehydration (most common); IV if severe (rarely)], children are discharged with saline lock IV (routine procedure across Canadian pediatric EDs).

2. Oral fluids (preferably electrolyte maintenance solutions) ad lib following ED discharge

3. Additional health assessments as required

4. Daily blood tests at a local laboratory with results conveyed daily to the site-investigator until outpatient discharge criteria achieved; no in-person assessment given logistics (i.e. distance), impact on family, and mirroring of standard practice A) 2 - 4 days since symptom onset AND rising platelet count (>5% increase) documented over 48 hours in a clinically well child B) ≥5 days since symptom onset AND stable platelet count (<5% decrease) documented over 48 hours in a clinically well child

Group Type: ACTIVE_COMPARATOR

Routine home oral rehydration

Intervention Type: DRUG

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

Interventions

D5-0.9%NS

Admission for intravascular volume expansion

Intervention Type: DRUG

Routine home oral rehydration

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

Intervention Type: DRUG

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)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Calgary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stephen Freedman, MDCM, MSc

Role: PRINCIPAL_INVESTIGATOR

University of Calgary

Locations

Alberta Children's Hospital

Calgary, Alberta, Canada

Countries

Canada

References

Imdad A, Nelson JR, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2025 Apr 25;4(4):CD012997. doi: 10.1002/14651858.CD012997.pub3.

Reference Type: DERIVED

PMID: 40277027 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34219224 (View on PubMed)

Other Identifiers

CHREB-12345

Identifier Type: -

Identifier Source: org_study_id