Hyperhydration in Children With Shiga Toxin-Producing E. Coli Infection (HIKO STEC)
M
Myda Khalid
Primary Investigator
Enrolling By Invitation
9-21 years
All
Phase
3
1040 participants needed
1 Location
Overview
The objective of this study is to determine if early high volume intravenous fluiddministration (hyperhydration) may be effective in mitigating or preventing complications ofhiga toxin-producing E. coli (STEC) infection in children and adolescents when compared withditional approaches (conservative fluid management).
Description
The hemolytic uremic syndrome (HUS) is the most serious complication of high-risk Shigaducing Escherichia coli (STEC) infection and the most common cause of acquired acute
kidney injury in otherwise healthy children. HUS develops in up to 20% of children followingTEC infection, 60% of whom require temporary renal replacement therapy (RRT); an additional
50% develop serious extrarenal complications. Although mortality from acute HUS is low
(1-3%), it has remained constant for three decades and approximately 30% of HUS survivorsg-term sequelae, chiefly chronic kidney disease, hypertension, and diabetes.
There have been only three relatively small, randomized trials to prevent progression to HUSd/or to reduce kidney injury once HUS is established; none have demonstrated benefits, andhave been performed since 1999.
Recent cohort studies suggest that early intravascular volume expansion (hyperhydration) inTEC infected children could be nephroprotective if and when HUS occurs. However, morevidence is needed before hyperhydration supplants traditional 'wait and see' (i.e.,vative fluid management) reactive care approaches which focus on outpatient care andzing intravenous fluid administration to avoid fluid overload in children who do
develop HUS. Here, we will confirm or refute the hypothesis that aggressive volume expansion,dministered early in STEC infected children, is associated with better renal outcomes andwer adverse events than conservative management by accomplishing three Specific Aims: (1)
Determine the effectiveness of hyperhydration in decreasing the prevalence of Major Adverse
Kidney Events by 30 days (defined as death, RRT, or sustained loss of kidney function at 30
days) in STEC-infected children versus conservative fluid management; (2) Determine theveness and safety of hyperhydration in decreasing HUS and life-threatening, extrarenalTEC-infected children versus conservative fluid management; (3) Create a
biorepository that will be linked to our clinical data to identify prognostic biomarkers andherapeutic targets in STEC-infected children.
Eligibility
You may be eligible for this study if you meet the following criteria:
-
Conditions:
Shiga Toxin-Producing Escherichia Coli (E. Coli) Infection, Hemolytic-Uremic Syndrome
-
Age: Between 9 Months - 21 Years
-
Gender: All
Inclusion Criteria:
In order to be eligible to participate in this study (i.e., to be enrolled in the relevant
institutional clinical care pathway), an individual must meet all of the following
criteria:
1. Aged 9.0 months to <21 years at the time of informed consent.
2. Evidence of high-risk STEC infecting pathogen defined by any of the following:
1. Bloody diarrhea within the preceding 7 days
- Positive STEC culture OR
- Positive antigen/polymerase chain reaction test for toxin/gene type not
otherwise specified OR
2. Bloody or Non-bloody diarrhea within the preceding 7 days
•Presumptive diagnosis of HUS
- (meeting all 3 HUS criteria - anemia, thrombocytopenia, and renal
insufficiency) OR
3. Non-bloody or no diarrhea
- Positive STEC culture for high-risk strain (i.e., O103, O104, O111, O113,
O121, O145 or O157) OR
- Positive antigen/polymerase chain reaction test Stx2 toxin/gene
Exclusion Criteria:
All individuals meeting any of the exclusion criteria at baseline will be excluded from
study participation.
1. Presence of Advanced HUS defined by:
1. Hematocrit <30% AND
2. Platelet count <150 x 103/mm3 AND
3. Creatinine > 2.0 mg/dL (177 µmol/L)
- The presence of only 1 or 2 of these criteria will not result in patient
exclusion, regardless of how close the 3rd criterion is to meeting the
exclusion criteria.
2. Prior episode of HUS or diagnosis of atypical HUS.
3. Chronic disease limiting fluid volumes administered (e.g. impaired renal, liver, or
cardiac function, chronic lung disease).
4. Evidence of anuria (i.e., no urine output for > 24 hours).
5. Hypoxemia requiring oxygen therapy
6. Hypertensive emergency
7. Greater than or equal to 10 days since onset of diarrhea or if no diarrhea then the
onset of other symptoms.
8. Patients with known pregnancy
9. Patients or caregivers with language barriers impairing appropriate conduct of the
study protocol.
Updated on
16 May 2024.
Study ID: DMID 21-0042, PNEPH-UTAH-HIKO-STEC, 13730
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