Recruiting

Hyperhydration

Sponsor:

University of Calgary

Code:

NCT05219110

Conditions

Shiga Toxin-Producing Escherichia Coli (E. Coli) Infection

Hemolytic-Uremic Syndrome

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

Interventions

Infusion of 200% maintenance fluids as balanced crystalloid IV solution

Oral fluids; infusion of up to 110% maintenance fluids as balanced crystalloid IV solution

Study Details

Brief 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).

Conditions

Shiga Toxin-Producing Escherichia Coli (E. Coli) Infection

Hemolytic-Uremic Syndrome

Study ID

NCT05219110

Start date

Sep 29, 2022

Status verified date

May, 2026

Completion date

Aug 31, 2028

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0 - 21

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

1040 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Hyperhydration

In this study arm, all eligible children are admitted for the administration of intravenous fluids.

The following specifics will form the basis of the fluid management protocol:

1. Reversal of dehydration: Initial ED rehydration strategies should focus on rapidly reversing dehydration.
2. Infusion of 200% of maintenance fluids x 24 hours
3. If hematocrit reduction < 20% from initial value, repeat step #2 \[infusion of 200% maintenance fluids x 24 hours\].
4. Oral fluids permitted ad lib.
5. Once the target hematocrit reduction is achieved (20% decrement in initial HCT) AND a 10% weight gain, adjust total IV fluid volume to maintain targeted weight gain: insensible plus output (i.e., urine plus stool).

active comparator: Conservative Fluid Management

The conservative fluid management arm has been designed to align and integrate into existing local practice patterns. Implementation of this approach will allow institutions and their practitioners to choose their management of protocol eligible children. All children will undergo a protocolized baseline evaluation that includes reversal of dehydration (if present) and follow-up plan (see Pre-Pathway care). The fluid management decision in the ED (i.e., to treat dehydration) will be at the discretion of the clinical care team. In the absence of evidence of microangiopathy (i.e., normal urinalysis, LDH, hemoglobin and platelet counts, and creatinine concentrations), the decision to admit the child to hospital or discharge the child to home will be at the discretion of the clinical care team. If microangiopathy is present (i.e., abnormal urinalysis, LDH, hemoglobin or platelet counts, or creatinine concentrations) admission for monitoring will be required.

Interventions

Infusion of 200% maintenance fluids as balanced crystalloid IV solution

Infusion of 200% of maintenance fluids x 24 hours provided, ideally, as a balanced crystalloid (PlasmaLyteTM, Ringer's Lactate) IV solution. Electrolytes and dextrose may be administered as required and desired by the clinical care team; customized solutions are permitted if so desired. Intravenous fluid solutions containing < 130 mEq/L sodium may increase risk for hyponatremia and may be less effective in achieving intravascular volume expansion and should be avoided.

Oral fluids; infusion of up to 110% maintenance fluids as balanced crystalloid IV solution

Administration of less than or equal to 110% of maintenance fluids as oral or balanced crystalloid IV solution.

Primary outcome measure

  • Major Adverse Kidney Events by 30 days (MAKE30) [ Time Frame: 30 days ]

Central Contacts and Locations

Central contacts

Locations

University of Alabama at Birmingham

Recruiting

Birmingham, Alabama, United States, 35294

Arkansas Children's Hospital

Recruiting

Little Rock, Arkansas, United States, 72202

University of California, San Diego

Recruiting

La Jolla, California, United States, 92093

University of California, Davis

Recruiting

Sacramento, California, United States, 95817

University of Colorado Denver

Recruiting

Denver, Colorado, United States, 80045

Children's Research Institute

Recruiting

Washington D.C., District of Columbia, United States, 20010

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Indiana University Children's Hospital

Recruiting

Indianapolis, Indiana, United States, 47401

University of Kentucky

Recruiting

Lexington, Kentucky, United States, 40526

Norton Children's Hospital

Recruiting

Louisville, Kentucky, United States, 40202

Children's Minnesota Hospital

Recruiting

Minneapolis, Minnesota, United States, 55404

Washington University

Recruiting

St Louis, Missouri, United States, 63110

Children's Hospital Medical Center

Recruiting

Cincinnati, Ohio, United States, 45229-3039

University Hospitals Rainbow Babies & Children's Hospital

Recruiting

Cleveland, Ohio, United States, 44106

Nationwide Children's Hospital

Recruiting

Columbus, Ohio, United States, 43205

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Oregon Health & Science University

Recruiting

Portland, Oregon, United States, 97239

Medical University of South Carolina

Recruiting

Charleston, South Carolina, United States, 29425

Vanderbilt Children's Hospital

Recruiting

Nashville, Tennessee, United States, 43205

Baylor College of Medicine

Recruiting

Houston, Texas, United States, 77030

University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Seattle Children's Hospital

Recruiting

Seattle, Washington, United States, 98105

Alberta Children's Hospital

Recruiting

Calgary, Alberta, Canada, T2N 1N4

University of Alberta

Recruiting

Edmonton, Alberta, Canada, T5J 4P6

McMaster University

Recruiting

Hamilton, Ontario, Canada, L8S 4K1

The Hospital for Sick Children

Recruiting

Toronto, Ontario, Canada, M5G 1X8

More Information

Sponsor

University of Calgary

Last update posted

May 18, 2026

Last verified

May, 2026

Keywords

  • Child
  • Hemolytic Uremic Syndrome
  • Shiga-Toxigenic Escherichia coli
  • Renal Replacement Therapy
  • Acute Kidney Injury
  • Ambulatory Care
  • Emergency Department

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of Calgary on 2026-05-18.