Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion

Hemolytic-Uremic Syndrome Clinical Trial

Official title:

Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03275792
• Other study ID #: CHREB-12345
• Status: Withdrawn
• Phase: Phase 1
• Start date: May 2020
• Est. completion date: April 2021

Study information

• Verified date: September 2019
• Source: University of Calgary
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hemolysis
• Hemolytic-Uremic Syndrome
• Syndrome

Intervention

Drug:
• D5-0.9%NS
Admission for intravascular volume expansion
• Routine home oral rehydration
Routine oral fluids as is given at home to all children with acute diarrheal disease

Locations

Country	Name	City	State
Canada	Alberta Children's Hospital	Calgary	Alberta

Sponsors (1)

Lead Sponsor	Collaborator
University of Calgary

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Point-of-Care STEC diagnosis	diagnostic accuracy compared with standard culture	at the end of the 24 month study recruiting period
Other	Urine biomarkers	ability to predict progression to AKI and HUS	at the end of the 24 month study recruiting period
Other	Point-of-Care STEC diagnosis	turnaround time	at the end of the 24 month study recruiting period
Other	Point-of-Care STEC diagnosis	proportion O157 vs other STEC	at the end of the 24 month study recruiting period
Primary	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.	at the end of the 24 month study recruiting period
Secondary	The proportion of children enrolled in each study arm who develop adverse events	For participants enrolled in each study arm we will quantify the proportion that are admitted to Intensive Care Units, the proportion requiring respiratory support (CPAP, BiPAP, endotracheal intubation), hypoxia defined by the administration of supplemental oxygen, and evidence of congestive heart failure defined by blinded independent reviewers.	at the end of the 24 month study recruiting period
Secondary	Retention	The proportion of children who complete the study protocol	at the end of the 24 month study recruiting period
Secondary	Time requirements	We will quantify the number of hours children remain admitted and to which clinical units	at the end of the 24 month study recruiting period
Secondary	Child/family perspectives	7-item likert scales will be employed to evaluate perspectives of parents and participants as appropriate related to study protocols, procedures and participation	at the end of the 24 month study recruiting period
Secondary	compliance/adherence	The proportion of children enrolled in each study arm who comply with the key interventions of the respective study arms	at the end of the 24 month study recruiting period
Secondary	data collection tool performance	Individual data fields will be audited with respect to data quality, reliability, completeness, timeliness of completion	at the end of the 24 month study recruiting period
Secondary	Impact on clinical services	We will qualitatively explore with the department leads at the respective institutions if the study protocol had any impact on clinical care provided either to the admitted patients or to other patients on their services	at the end of the 24 month study recruiting period
Secondary	Cost	We will quantify the costs per child in each study arm	at the end of the 24 month study recruiting period