Hyperhydration in Children With Shiga Toxin-Producing E. Coli Infection
HIKO-STEC
Hyperhydration to Improve Kidney Outcomes in Children With Shiga Toxin-Producing E. Coli Infection: A Multinational Embedded Cluster Crossover Randomized Trial
2 other identifiers
interventional
1,040
2 countries
26
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Sep 2022
Longer than P75 for not_applicable
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 20, 2022
CompletedFirst Posted
Study publicly available on registry
February 1, 2022
CompletedStudy Start
First participant enrolled
September 29, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2027
June 5, 2025
December 1, 2024
3.9 years
January 20, 2022
June 2, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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)
30 days
Secondary Outcomes (2)
Number of Participants with Significant Extrarenal Complications (life-threatening):
30 days
Number of Participants who Develop HUS among those without it at randomization
30 days
Other Outcomes (3)
Length of Stay
30 days
Number of Participants who Receive Transfusion Therapy
30 days
Number of Participants who Receive Invasive Medical Procedures
30 days
Study Arms (2)
Hyperhydration
EXPERIMENTALIn 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).
Conservative Fluid Management
ACTIVE COMPARATORThe 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% 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.
Eligibility Criteria
You may qualify if:
- 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:
- Aged 9.0 months to \<21 years at the time of informed consent.
- Evidence of high-risk STEC infecting pathogen defined by any of the following:
- 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
- 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 may not qualify if:
- Presence of Advanced HUS defined by:
- Hematocrit \<30% AND
- Platelet count \<150 x 103/mm3 AND
- Creatinine \> 2.0 mg/dL (177 µmol/L)
- Prior episode of HUS or diagnosis of atypical HUS.
- Chronic disease limiting fluid volumes administered (e.g. impaired renal, liver, or cardiac function, chronic lung disease).
- Evidence of anuria (i.e., no urine output for \> 24 hours).
- Hypoxemia requiring oxygen therapy
- Hypertensive emergency
- Greater than or equal to 10 days since onset of diarrhea or if no diarrhea then the onset of other symptoms.
- Patients with known pregnancy
- Patients or caregivers with language barriers impairing appropriate conduct of the study protocol.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Calgarylead
- National Institute of Allergy and Infectious Diseases (NIAID)collaborator
- Children's Hospital Medical Center, Cincinnaticollaborator
- Washington University School of Medicinecollaborator
- University of Utahcollaborator
- Seattle Children's Hospitalcollaborator
- University of Colorado, Denvercollaborator
- Emory Universitycollaborator
- University of California, Daviscollaborator
- Baylor College of Medicinecollaborator
- Indiana University School of Medicinecollaborator
- University of Alabama at Birminghamcollaborator
- Arkansas Children's Hospital Research Institutecollaborator
- Children's National Research Institutecollaborator
- Children's Hospitals and Clinics of Minnesotacollaborator
- Medical University of South Carolinacollaborator
- University of Louisvillecollaborator
- University of Oklahomacollaborator
- Oregon Health and Science Universitycollaborator
- University of California, San Diegocollaborator
- McMaster Universitycollaborator
- The Hospital for Sick Childrencollaborator
- University of Albertacollaborator
- University of Kentuckycollaborator
- Case Western Reserve Universitycollaborator
- Nationwide Children's Hospitalcollaborator
- Vanderbilt University Medical Centercollaborator
Study Sites (26)
University of Alabama at Birmingham
Birmingham, Alabama, 35294, United States
Arkansas Children's Hospital
Little Rock, Arkansas, 72202, United States
University of California, San Diego
La Jolla, California, 92093, United States
University of California, Davis
Sacramento, California, 95817, United States
University of Colorado Denver
Denver, Colorado, 80045, United States
Children's Research Institute
Washington D.C., District of Columbia, 20010, United States
Emory University
Atlanta, Georgia, 30322, United States
Indiana University Children's Hospital
Indianapolis, Indiana, 47401, United States
University of Kentucky
Lexington, Kentucky, 40526, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Children's Minnesota Hospital
Minneapolis, Minnesota, 55404, United States
Washington University
St Louis, Missouri, 63110, United States
Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039, United States
University Hospitals Rainbow Babies & Children's Hospital
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, 43205, United States
Baylor College of Medicine
Houston, Texas, 77030, United States
University of Utah
Salt Lake City, Utah, 84112, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Alberta Children's Hospital
Calgary, Alberta, T2N 1N4, Canada
University of Alberta
Edmonton, Alberta, T5J 4P6, Canada
McMaster University
Hamilton, Ontario, L8S 4K1, Canada
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
Related Publications (2)
Imdad A, Nelson JR, Tanner-Smith EE, Huang D, Gomez-Duarte OG. Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome. Cochrane Database Syst Rev. 2025 Apr 25;4(4):CD012997. doi: 10.1002/14651858.CD012997.pub3.
PMID: 40277027DERIVEDFreedman SB, Schnadower D, Estes M, Casper TC, Goldstein SL, Grisaru S, Pavia AT, Wilfond BS, Metheney M, Kimball K, Tarr PI; Hyperhydration to Improve Kidney Outcomes in children with Shiga Toxin-producing E. Coli infection (HIKO-STEC) Study Team. Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial). Trials. 2023 May 27;24(1):359. doi: 10.1186/s13063-023-07379-w.
PMID: 37245030DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen Freedman, MDCM
University of Calgary
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 20, 2022
First Posted
February 1, 2022
Study Start
September 29, 2022
Primary Completion (Estimated)
August 31, 2026
Study Completion (Estimated)
August 31, 2027
Last Updated
June 5, 2025
Record last verified: 2024-12
Data Sharing
- IPD Sharing
- Will not share