Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion

NCT03275792 | Withdrawn Phase 1 DMC

• 1 other identifier: CHREB-12345
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemolytic-Uremic Syndrome

Keywords

Shiga-Toxigenic Escherichia coli; Child

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• The proportion of children enrolled in each study arm who develop adverse events

  at the end of the 24 month study recruiting period

• Retention

  at the end of the 24 month study recruiting period

• Time requirements

  at the end of the 24 month study recruiting period

• Child/family perspectives

  at the end of the 24 month study recruiting period

• compliance/adherence

  at the end of the 24 month study recruiting period

Other Outcomes (4)

• Point-of-Care STEC diagnosis

  at the end of the 24 month study recruiting period

• Urine biomarkers

  at the end of the 24 month study recruiting period

• Point-of-Care STEC diagnosis

  at the end of the 24 month study recruiting period

Study Arms (2)

Admission/Intravascular Volume Expansion

EXPERIMENTAL

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.

Drug: D5-0.9%NS

Outpatient Observation

ACTIVE COMPARATOR

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

Drug: Routine home oral rehydration

Interventions

D5-0.9%NS DRUG

Admission for intravascular volume expansion

Admission/Intravascular Volume Expansion

Routine home oral rehydration DRUG

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

Outpatient Observation

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age \<18.0 years;
• STEC infection \[positive culture OR antigen OR polymerase chain reaction test for Stx/gene\];
• 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.

You may not qualify if:

• Evidence of evolving HUS: A) Hematocrit \<30% OR B) Platelet count \<150 x 109/L;
• Responsible physician desires patient admission (therefore unable to randomize);
• Unable to contact family within 48 hours of positive stool test;
• Patient with history of atypical HUS;
• Chronic disease limiting fluid volumes administered (e.g. impaired cardiac function)

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Related Publications (2)

• 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.

  PMID: 40277027 DERIVED

• 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.

  PMID: 34219224 DERIVED

MeSH Terms

Conditions

Hemolytic-Uremic Syndrome

Condition Hierarchy (Ancestors)

Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia

Study Officials

• Stephen Freedman, MDCM, MSc

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2017
• First Posted: September 8, 2017
• Study Start: May 1, 2020
• Primary Completion: April 1, 2021
• Study Completion: April 1, 2021
• Last Updated: November 9, 2020

Record last verified: 2019-09

Locations

CA (1)