Hyperhydration for E. coli Infections

(HIKO-STEC Trial)

Recruiting at 25 trial locations

Overseen By Study Manager

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Calgary

Disqualifiers: Advanced HUS, Chronic disease, Anuria, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 4 weeks

1040 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if early, large-volume fluid administration can reduce complications from certain E. coli infections in children and teens. The study compares this hyperhydration approach (infusion of 200% maintenance fluids as a balanced crystalloid IV solution) to standard fluid management practices. Participants will receive either a high volume of IV fluids or a more conservative amount, with effects monitored throughout. Children and teens who have recently experienced bloody diarrhea and tested positive for a high-risk E. coli strain may be suitable candidates for the trial. As an unphased trial, this study allows participants to contribute to important research that could enhance treatment strategies for future patients.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that giving children with E. coli infections extra fluids through an IV is under study for safety and effectiveness. This method, called hyperhydration, uses more fluids than usual to prevent complications. In past studies, children received up to twice the normal amount of fluids.

Early results suggest hyperhydration is generally safe, but close monitoring for side effects is crucial. Some studies have found that high fluid intake may improve kidney health, but more research is needed to confirm these benefits and ensure safety.

So far, no major reports of serious problems have been directly linked to this treatment. However, as with any medical treatment, healthcare providers must closely monitor for any unexpected reactions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the hyperhydration protocol for E. coli infections because it uses an aggressive fluid management strategy, which is different from the conservative fluid management typically used in such cases. Standard treatments for E. coli infections often focus on rehydration and symptomatic relief, but this approach emphasizes rapid rehydration and a significant increase in fluid intake, aiming for a 200% increase over traditional maintenance levels. This method could potentially lead to quicker recovery by efficiently reversing dehydration and achieving rapid weight gain, which are critical in managing the symptoms of E. coli infections. The trial aims to determine if this approach can improve outcomes for children with E. coli infections compared to existing treatment practices.

What evidence suggests that hyperhydration might be an effective treatment for E. coli infections?

Research has shown that administering more fluids than usual through an IV, known as hyperhydration, might help children with E. coli infections by reducing complications. In this trial, one arm involves hyperhydration, where children receive an infusion of 200% maintenance fluids. Studies have found that starting high-volume fluid treatments early can decrease the severity of kidney problems. For instance, past data indicates that 10% of children who receive standard fluid treatment experience major complications, suggesting that hyperhydration could lead to better outcomes. This method focuses on quickly reversing dehydration and maintaining fluid balance, which might help children recover more effectively. Overall, more fluids could lessen the infection's impact on the body. ^{1 2 3 4 6}

Who Is on the Research Team?

Stephen Freedman, MDCM

Principal Investigator

University of Calgary

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 9 months to under 21 years with a high-risk strain of E. coli infection that may lead to Hemolytic Uremic Syndrome (HUS). They must have symptoms like diarrhea or anemia, low platelet count, and kidney issues. It's not for those who are pregnant, have chronic diseases affecting fluid intake, started showing symptoms over 10 days ago, need oxygen therapy due to low blood oxygen levels, haven't urinated in over 24 hours, had HUS before or have severe HUS.

Inclusion Criteria

I have a severe E. coli infection confirmed by tests.

I am between 9 months and 21 years old.

I tested positive for a dangerous E. coli strain.

Exclusion Criteria

I need oxygen therapy due to low blood oxygen levels.

You are pregnant.

I have had HUS or been diagnosed with atypical HUS before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either conservative fluid management or hyperhydration to manage STEC infection

4 weeks

Weekly monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on kidney outcomes and adverse events

4 weeks

2 visits (in-person)

Long-term Follow-up

Participants are monitored for long-term sequelae such as chronic kidney disease, hypertension, and diabetes

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Infusion of 200% maintenance fluids as balanced crystalloid IV solution
• Infusion of up to 110% maintenance fluids as balanced crystalloid IV solution
• Oral fluids

Trial Overview The study tests if giving lots of IV fluids early on (hyperhydration) can help kids with serious E. coli infections better than the usual amount of fluids. One group gets double the normal fluid rate through an IV; another gets up to just a bit more than normal plus oral fluids.

How Is the Trial Designed?

Group I: Hyperhydration Experimental Treatment 1 Intervention

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).

Group II: Conservative Fluid Management Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Calgary

Lead Sponsor

Trials

827

Recruited

902,000+

Indiana University School of Medicine

Collaborator

Trials

194

Recruited

181,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Case Western Reserve University

Collaborator

Trials

314

Recruited

236,000+

Children's National Research Institute

Collaborator

Trials

227

Recruited

258,000+

Seattle Children's Hospital

Collaborator

Trials

319

Recruited

5,232,000+

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

University of Kentucky

Collaborator

Trials

198

Recruited

224,000+

Nationwide Children's Hospital

Collaborator

Trials

354

Recruited

5,228,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Published Research Related to This Trial

Balanced crystalloid solutions, like lactated Ringer's and Plasma-Lyte, are increasingly preferred over saline (0.9% sodium chloride) for intravenous fluid therapy in acutely ill patients due to their closer resemblance to extracellular fluid and fewer adverse effects on acid-base balance.

Research indicates that using balanced crystalloids can prevent hyperchloremic metabolic acidosis and may lower the risk of complications such as acute kidney injury and death compared to saline, suggesting a need to reconsider saline as the primary intravenous fluid in critical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balanced Crystalloid Solutions. Semler, MW., Kellum, JA.[2022]

Infusing 0.9% saline, which has equal concentrations of sodium (Na+) and chloride (Cl-), can lead to hyperchloremic acidosis, potentially affecting critically ill patients, but the clinical significance of this effect is still unclear.

Observational data suggest that using fluids with lower chloride concentrations may reduce risks of renal dysfunction, infections, and possibly mortality, highlighting the need for large randomized trials to confirm these associations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balanced versus unbalanced salt solutions: what difference does it make? Magder, S.[2018]

Balanced intravenous solutions, which have an electrolyte composition similar to plasma, are thought to minimize disruptions in acid-base balance compared to standard saline solutions, which can cause hyperchloremic metabolic acidosis.

Recent large-scale studies, including the SPLIT trial, indicate that balanced solutions do not show significant advantages over unbalanced solutions in terms of renal function in critically ill patients, suggesting that the search for an ideal balanced solution is ongoing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous balanced solutions: from physiology to clinical evidence. Langer, T., Santini, A., Scotti, E., et al.[2022]

In a review of 13 studies involving nearly 31,000 critically ill adults, balanced crystalloids were associated with lower hospital and 28-/30-day mortality rates compared to 0.9% sodium chloride (saline), suggesting they may be a safer option for fluid resuscitation.

Balanced crystalloids also resulted in a lower incidence of new acute kidney injury compared to saline, indicating they may be more effective in protecting kidney function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis. Hammond, DA., Lam, SW., Rech, MA., et al.[2020]

In a study involving 15,802 critically ill adults, the use of balanced crystalloids (like lactated Ringer's solution) resulted in a lower rate of major adverse kidney events compared to saline, with 14.3% of patients in the balanced group experiencing such events versus 15.4% in the saline group.

The findings suggest that balanced crystalloids may be a safer option for intravenous fluid administration in critically ill patients, as they were associated with a marginally lower risk of death, new renal-replacement therapy, or persistent renal dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balanced Crystalloids versus Saline in Critically Ill Adults. Semler, MW., Self, WH., Wanderer, JP., et al.[2022]

In critically ill patients, aiming for 'normal' plasma volume and electrolyte levels may not be the best approach, as a hyperosmolar state can help reduce tissue swelling in conditions like brain injury and major surgery.

Crystalloid solutions are more effective than vasopressors for treating shock from blunt trauma and are at least as effective as colloids in septic shock, suggesting that traditional resuscitation guidelines may need to be reevaluated to avoid excessive fluid administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isotonic and hypertonic crystalloid solutions in the critically ill. Bauer, M., Kortgen, A., Hartog, C., et al.[2019]

In a meta-analysis of six trials involving 34,685 ICU patients, balanced crystalloids showed a high probability of reducing in-hospital mortality compared to saline, although the absolute risk reduction was small (0.4 percentage points).

However, in patients with traumatic brain injury, balanced solutions were associated with increased in-hospital mortality, indicating that their use may not be beneficial in this specific subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Balanced crystalloids versus saline for critically ill patients (BEST-Living): a systematic review and individual patient data meta-analysis. Zampieri, FG., Cavalcanti, AB., Di Tanna, GL., et al.[2023]

The BaSICS trial will involve 11,000 critically ill patients across over 100 Brazilian intensive care units to compare the effects of balanced crystalloid solutions (Plasma-Lyte 148) versus saline on 90-day all-cause mortality.

The study will also investigate whether the rate of fluid infusion (rapid vs. slow) impacts patient outcomes, including renal failure and organ dysfunction, providing valuable insights into fluid management in critical care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for the Balanced Solution versus Saline in Intensive Care Study (BaSICS): a factorial randomised trial. Zampieri, FG., Azevedo, LCP., Corrêa, TD., et al.[2022]

Semisynthetic colloids, while having greater intravascular persistence, are associated with a higher risk of renal failure and increased mortality, suggesting their use should be limited in clinical practice.

Balanced crystalloids are preferred over normal saline due to their lower association with metabolic acidosis and renal complications, making them a better first-choice option for fluid resuscitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A critical appraisal of intravenous fluids: from the physiological basis to clinical evidence. Severs, D., Hoorn, EJ., Rookmaaker, MB.[2022]

In a study of 79 pediatric patients with severe sepsis or septic shock, higher administration of crystalloid fluids (over 193 mL/kg) was associated with increased mortality and longer stays in the pediatric intensive care unit (PICU).

Patients receiving high volumes of crystalloids also experienced more days on mechanical ventilation, indicating that excessive fluid administration may negatively impact postoperative outcomes in children with sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crystalloid fluid administration was associated with outcomes in pediatric patients with severe sepsis or septic shock. Zhang, S., Dai, X., Guo, C.[2022]

In a study of 10,520 ICU patients, the use of a balanced crystalloid solution (Plasma-Lyte 148) showed a high probability of reducing 90-day mortality for patients who received only balanced solutions before enrollment, particularly benefiting those with unplanned admissions due to sepsis.

Overall, while the balanced solution did not show a significant mortality benefit for the entire trial population, it was associated with improved outcomes for specific groups, indicating that prior fluid use and admission type can influence clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial. Zampieri, FG., Machado, FR., Biondi, RS., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05219110

Hyperhydration in Children With Shiga Toxin-Producing E. ... The objective of this study is to determine if early high volume intravenous fluid administration (hyperhydration) may be effective in mitigating or ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10224603/

Hyperhydration to Improve Kidney Outcomes in Children with ... Observational studies have shown that early high-volume intravenous fluid administration (hyperhydration) is associated with reduced severity of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37245030/

Hyperhydration to Improve Kidney Outcomes in Children with ... Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome.

4. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT05219110

Hyperhydration in Children With Shiga Toxin-Producing E ... The objective of this study is to determine if early high volume intravenous fluid administration (hyperhydration) may be effective in mitigating or preventing ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/541896

Hyperhydration in Children With Shiga Toxin-Producing E. ... The objective of this study is to determine if early high volume intravenous fluid administration (hyperhydration) may be effective in ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05219110/hyperhydration-in-children-with-shiga-toxin-producing-e-coli-infection

Hyperhydration in Children With Shiga Toxin-Producing E. ... The objective of this study is to determine if early high volume intravenous fluid administration (hyperhydration) may be effective in mitigating or preventing ...