Summary

Eligibility
for people ages 9 months to 21 years (full criteria)
Location
at La Jolla, California and other locations
Dates
study started
estimated completion

Description

Summary

The objective of this study is to determine if early high volume intravenous fluid administration (hyperhydration) may be effective in mitigating or preventing complications of shiga toxin-producing E. coli (STEC) infection in children and adolescents when compared with traditional approaches (conservative fluid management).

Official Title

Hyperhydration to Improve Kidney Outcomes in Children With Shiga Toxin-Producing E. Coli Infection: A Multinational Embedded Cluster Crossover Randomized Trial

Details

The hemolytic uremic syndrome (HUS) is the most serious complication of high-risk Shiga toxin-producing 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 following STEC 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 survivors experience long-term sequelae, chiefly chronic kidney disease, hypertension, and diabetes. There have been only three relatively small, randomized trials to prevent progression to HUS and/or to reduce kidney injury once HUS is established; none have demonstrated benefits, and none have been performed since 1999. Recent cohort studies suggest that early intravascular volume expansion (hyperhydration) in STEC infected children could be nephroprotective if and when HUS occurs. However, more evidence is needed before hyperhydration supplants traditional 'wait and see' (i.e., conservative fluid management) reactive care approaches which focus on outpatient care and minimizing 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, administered early in STEC infected children, is associated with better renal outcomes and fewer 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 the effectiveness and safety of hyperhydration in decreasing HUS and life-threatening, extrarenal complications in STEC-infected children versus conservative fluid management; (3) Create a biorepository that will be linked to our clinical data to identify prognostic biomarkers and therapeutic targets in STEC-infected children.

Keywords

Shiga Toxin-Producing Escherichia Coli (E. Coli) Infection Hemolytic-Uremic Syndrome Child Hemolytic Uremic Syndrome Shiga-Toxigenic Escherichia coli Renal Replacement Therapy Acute Kidney Injury Ambulatory Care Emergency Department Infections Communicable Diseases Escherichia coli Infections Hemolysis Pharmaceutical Solutions Infusion of 200% maintenance fluids as balanced crystalloid IV solution Oral fluids; infusion of up to 110% maintenance fluids as balanced crystalloid IV solution Hyperhydration Conservative Fluid Management

Eligibility

You can join if…

Open to people ages 9 months to 21 years

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:
  3. Bloody diarrhea within the preceding 7 days
  4. Positive STEC culture OR
  5. Positive antigen/polymerase chain reaction test for toxin/gene type not otherwise specified OR
  6. 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
  • 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

You CAN'T join if...

All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation.

  1. Presence of Advanced HUS defined by:
  2. Hematocrit <30% AND
  3. Platelet count <150 x 103/mm3 AND
  4. Creatinine > 2.0 mg/dL (177 µmol/L)
  5. 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.

  1. Prior episode of HUS or diagnosis of atypical HUS.
  2. Chronic disease limiting fluid volumes administered (e.g. impaired liver or cardiac function, chronic lung disease).
  3. Evidence of anuria (i.e., no urine output for > 24 hours).
  4. Hypoxemia requiring oxygen therapy
  5. Hypertensive emergency
  6. Greater than or equal to 10 days since onset of diarrhea or if no diarrhea then the onset of other symptoms.
  7. Patients with known CAKUT (congenital anomalies of the kidney and urinary tract), including kidney anomalies, renal hypo dysplasia, ectopic kidney, horseshoe kidney, multicystic dysplastic kidney, hydronephrosis, duplicated collecting system, ureteropelvic junction obstruction, megaureter, vesicoureteral reflux, and posterior urethral valve.
  8. Patients with known pregnancy
  9. . Patients or caregivers with language barriers impairing appropriate conduct of the study protocol.

Locations

  • University of California, San Diego
    La Jolla California 92093 United States
  • University of California, Davis
    Sacramento California 95817 United States

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of Calgary
ID
NCT05219110
Phase
Phase 3 Hemolytic-Uremic Syndrome Research Study
Study Type
Interventional
Participants
Expecting 1040 study participants
Last Updated