An interventional study of Infusion of 200% maintenance fluids as balanced crystalloid IV solution and Oral fluids; infusion of up to 110% maintenance fluids as balanced crystalloid IV solution in Shiga Toxin-Producing Escherichia Coli (E. Coli) Infection and Hemolytic-Uremic Syndrome, sponsored by University of Calgary. Recruiting at 26 sites in 2 countries. Open to participants aged 9 Months to 21 Years. Per ClinicalTrials.gov, last updated 2026-05-18.
Sponsored by University of Calgary · Not applicable, Interventional, and Treatment
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).
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.
99 studies on the registry are indexed under Escherichia coli Infections; 21 are open to participants now.
This study's planned enrollment of 1,040 is above the median of 72 across 63 interventional studies indexed under Escherichia coli Infections.
Browse Escherichia coli Infections studies →University of Calgary is the lead sponsor of 703 studies on the registry; 196 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 2 (20%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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:
Evidence of high-risk STEC infecting pathogen defined by any of the following:
Bloody diarrhea within the preceding 7 days
Bloody or Non-bloody diarrhea within the preceding 7 days
•Presumptive diagnosis of HUS
Non-bloody or no diarrhea
Exclusion Criteria:
All individuals meeting any of the exclusion criteria at baseline will be excluded from study participation.
Presence of Advanced HUS defined by:
Creatinine > 2.0 mg/dL (177 µmol/L)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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).
Other: Infusion of 200% maintenance fluids as balanced crystalloid IV solution
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.
Other: Oral fluids; infusion of up to 110% 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.
Administration of less than or equal to 110% of maintenance fluids as oral or balanced crystalloid IV solution.
Major Adverse Kidney Events by 30 days (MAKE30)
1. Death due to any cause censored at 30 days after enrollment OR 2. Provision of RRT, any modality, within 30 days of trial enrollment OR 3. Sustained loss of kidney function (100% increase of serum sCr from baseline at 30±7 days)
Time frame: 30 days
Number of Participants with Significant Extrarenal Complications (life-threatening):
a. Neurologic: i. Seizures requiring anticonvulsant therapy ii. Coma iii. Thrombotic or hemorrhagic stroke confirmed by neuroimaging b. Cardiac: i. Myocardial infarction ii. Myocarditis iii. Myocardial dysfunction iv. Arrhythmias requiring cardioversion or pharmacological anti-arrhythmic therapy c. Respiratory: i. Respiratory failure ii. Pleural effusions d. Gastrointestinal: i. Hyperglycemia requiring prolonged insulin therapy ii. Bowel obstruction/perforation requiring surgical repair iii. Intussusception requiring reduction iv. Acute cholecystitis v. Pancreatitis vi. Hepatitis/ liver failure vii. Ascites requiring paracentesis e. Infectious complications i. Bacteremia ii. Peritonitis
Time frame: 30 days
Number of Participants who Develop HUS among those without it at randomization
1. Anemia (hematocrit level \<30%) AND 2. Thrombocytopenia (platelet count \<150 X 103/mm3) AND 3. Renal azotemia (serum creatinine concentration \>upper limit of reference range for age)
Time frame: 30 days
Length of Stay
1. Number of days as an inpatient 2. Number of days in an intensive care unit (a unit capable of providing mechanical ventilation) 3. Hospital-Free Days: Measured as the number of calendar days alive and out of the hospital between randomization (day 0) and day 30. Patients who die prior to hospital discharge will be recorded as zero hospital-free days. 4. Score each hospital day * \# days with HUS with RRT * \# days with HUS without RRT * \# days in hospital - no HUS
Time frame: 30 days
Number of Participants who Receive Transfusion Therapy
1. Red Blood Cell 2. Platelets
Time frame: 30 days
Number of Participants who Receive Invasive Medical Procedures
1. Mechanical ventilation 2. Endotracheal intubation 3. Thoracentesis, thoracotomy, ARDS 4. Central venous catheter insertion 5. Dialysis catheter insertion 6. Therapeutic plasma exchange 7. Other operative room surgical interventions
Time frame: 30 days
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.