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Shiga Toxin Producing Escherichia Coli (STEC) Volume Expansion

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ClinicalTrials.gov Identifier: NCT03275792
Recruitment Status : Withdrawn (Funding not obtained.)
First Posted : September 8, 2017
Last Update Posted : November 9, 2020
Sponsor:
Information provided by (Responsible Party):
University of Calgary

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.

Condition or disease Intervention/treatment Phase
Hemolytic-Uremic Syndrome Drug: D5-0.9%NS Drug: Routine home oral rehydration Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Inpatient Volume Expansion in Children With Shiga Toxin-Producing Escherichia Coli (STEC) Infection to Prevent Hemolytic Uremic Syndrome (HUS)
Estimated Study Start Date : May 2020
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : April 2021


Arm Intervention/treatment
Experimental: 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.
Drug: D5-0.9%NS
Admission for intravascular volume expansion

Active Comparator: 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
Drug: Routine home oral rehydration
Routine oral fluids as is given at home to all children with acute diarrheal disease




Primary Outcome Measures :
  1. Number of children enrolled in the study protocol [ Time Frame: at the end of the 24 month study recruiting period ]
    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.


Secondary Outcome Measures :
  1. The proportion of children enrolled in each study arm who develop adverse events [ Time Frame: at the end of the 24 month study recruiting period ]
    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.

  2. Retention [ Time Frame: at the end of the 24 month study recruiting period ]
    The proportion of children who complete the study protocol

  3. Time requirements [ Time Frame: at the end of the 24 month study recruiting period ]
    We will quantify the number of hours children remain admitted and to which clinical units

  4. Child/family perspectives [ Time Frame: at the end of the 24 month study recruiting period ]
    7-item likert scales will be employed to evaluate perspectives of parents and participants as appropriate related to study protocols, procedures and participation

  5. compliance/adherence [ Time Frame: at the end of the 24 month study recruiting period ]
    The proportion of children enrolled in each study arm who comply with the key interventions of the respective study arms

  6. data collection tool performance [ Time Frame: at the end of the 24 month study recruiting period ]
    Individual data fields will be audited with respect to data quality, reliability, completeness, timeliness of completion

  7. Impact on clinical services [ Time Frame: at the end of the 24 month study recruiting period ]
    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

  8. Cost [ Time Frame: at the end of the 24 month study recruiting period ]
    We will quantify the costs per child in each study arm


Other Outcome Measures:
  1. Point-of-Care STEC diagnosis [ Time Frame: at the end of the 24 month study recruiting period ]
    diagnostic accuracy compared with standard culture

  2. Urine biomarkers [ Time Frame: at the end of the 24 month study recruiting period ]
    ability to predict progression to AKI and HUS

  3. Point-of-Care STEC diagnosis [ Time Frame: at the end of the 24 month study recruiting period ]
    turnaround time

  4. Point-of-Care STEC diagnosis [ Time Frame: at the end of the 24 month study recruiting period ]
    proportion O157 vs other STEC



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Ages Eligible for Study:   6 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03275792


Locations
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Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Sponsors and Collaborators
University of Calgary
Investigators
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Principal Investigator: Stephen Freedman, MDCM, MSc University of Calgary
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Calgary
ClinicalTrials.gov Identifier: NCT03275792    
Other Study ID Numbers: CHREB-12345
First Posted: September 8, 2017    Key Record Dates
Last Update Posted: November 9, 2020
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Calgary:
Shiga-Toxigenic Escherichia coli
Child
Additional relevant MeSH terms:
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Hemolytic-Uremic Syndrome
Syndrome
Hemolysis
Disease
Pathologic Processes
Uremia
Kidney Diseases
Urologic Diseases
Anemia, Hemolytic
Anemia
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders