1096 Participants Needed

Crystalloid Solutions for Septic Shock

(FISSH Trial)

Recruiting at 29 trial locations
PA
BR
Overseen ByBram Rochwerg, MSc,MD,FRCPC
Age: Any Age
Sex: Any
Trial Phase: Phase 2 & 3
Sponsor: McMaster University
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

This trial tests if a different type of fluid is safer and more effective for patients with serious infections. It aims to see if this new fluid can reduce harm to organs and help patients live longer.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of this treatment for septic shock?

Research suggests that using balanced crystalloids like lactated Ringer's solution or Plasma-Lyte A instead of normal saline may improve outcomes for sepsis patients, as they are associated with lower risks of kidney injury and metabolic issues.12345

Is it safe to use crystalloid solutions like normal saline or balanced crystalloids in humans?

Crystalloid solutions like normal saline and balanced crystalloids (such as Lactated Ringer's and Plasma-Lyte A) are generally safe for use in humans, but there are concerns about normal saline potentially causing issues like metabolic acidosis (a condition where the body produces too much acid) and kidney problems. Balanced crystalloids are often considered safer and may be preferred in some medical situations.12678

How does the treatment with crystalloid solutions for septic shock differ from other treatments?

This treatment uses balanced crystalloids like lactated Ringer's solution or Plasma-Lyte A, which may improve outcomes in septic shock by avoiding the high chloride levels and potential kidney issues associated with normal saline.1291011

Research Team

BR

Bram Rochwerg, MSc,MD,FRCPC

Principal Investigator

McMaster University

Eligibility Criteria

The FISSH trial is for patients aged 16 or older who are suspected of having an infection, within 6 hours of hospital admission, and need ICU care due to low blood pressure or organ issues after initial fluid treatment. Excluded are those with major burns, bleeding as the main issue, no commitment to life support, prior enrollment in FISSH or similar trials, end-stage kidney disease on dialysis, brain bleeds/hypertension during current stay.

Inclusion Criteria

I was admitted to the hospital or seen by a critical care team less than 6 hours ago.
I am 16 or older and need fluids for low blood pressure or poor organ blood flow.
are anticipated to require ICU admission
See 1 more

Exclusion Criteria

I have burns covering 10% of my body.
My low blood pressure is likely due to bleeding.
You are not willing to receive life support if needed.
See 5 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous fluids with either high or low chloride concentration for resuscitation in septic shock

up to 30 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including mortality, kidney failure, and length of ICU stay

up to 30 days

Treatment Details

Interventions

  • Higher Chloride Crystalloid
  • Lower Chloride Crystalloid
Trial OverviewThis study compares two types of IV fluids used in septic shock: one with higher chloride levels (normal saline) and another with lower chloride levels. It's a randomized controlled trial focusing on how these fluids affect mortality rates and acute kidney injury.
Participant Groups
2Treatment groups
Active Control
Group I: lower chloride solutionsActive Control1 Intervention
lower chloride crystalloid (Ringer's lactate - chloride concentration 110 mmol/L)
Group II: higher chloride solutionsActive Control1 Intervention
higher chloride crystalloid (Normal saline - chloride concentration 154 mmol/L)

Higher Chloride Crystalloid is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺
Approved in European Union as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement
🇺🇸
Approved in United States as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement
🇨🇦
Approved in Canada as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement
🇯🇵
Approved in Japan as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement
🇨🇳
Approved in China as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement
🇨🇭
Approved in Switzerland as Normal Saline for:
  • Resuscitation in septic shock
  • General fluid replacement

Find a Clinic Near You

Who Is Running the Clinical Trial?

McMaster University

Lead Sponsor

Trials
936
Recruited
2,630,000+

The Physicians' Services Incorporated Foundation

Collaborator

Trials
165
Recruited
31,700+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials
1,417
Recruited
26,550,000+

Findings from Research

In a study of 1,641 ICU patients with sepsis, using balanced crystalloids (like lactated Ringer's solution) instead of saline showed a significant reduction in 30-day in-hospital mortality when fluid choice was managed from the emergency department (ED) through to the ICU.
Specifically, during the ED and ICU period, the mortality rate was 24.9% for patients receiving balanced crystalloids compared to 30.6% for those receiving saline, indicating that early intervention with balanced crystalloids may improve outcomes for sepsis patients.
Effect of Early Balanced Crystalloids Before ICU Admission on Sepsis Outcomes.Jackson, KE., Wang, L., Casey, JD., et al.[2022]
In a study of 120 septic patients in the emergency department, there was no significant difference in lactate clearance between those treated with lactated Ringer's solution (LRS) and normal saline solution (NSS) after 2 hours of resuscitation.
Both LRS and NSS resulted in similar changes in serum creatinine levels and 48-hour survival rates, indicating that neither solution was superior in these outcomes for septic patients.
Normal Saline Solution or Lactated Ringer's Solution to Enhance Lactate Clearance in Septic Patients After Initial Resuscitation in the ED: A Retrospective Cohort Trial.Limapichat, T., Pattanapong, K.[2022]
In a study of 2022 sepsis patients, there was no significant difference in 30-day mortality, hospital length of stay, or need for mechanical ventilation between those receiving Lactated Ringer's (LR) and those receiving Normal Saline (NS) as their primary resuscitation fluid.
Although patients receiving LR had a longer hospital stay and higher ICU admission rates initially, these differences were not statistically significant after adjusting for multiple factors, indicating that both fluids may be similarly effective in managing sepsis.
A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis.Isha, S., Satashia, PH., Yarrarapu, SNS., et al.[2023]

References

Effect of Early Balanced Crystalloids Before ICU Admission on Sepsis Outcomes. [2022]
Normal Saline Solution or Lactated Ringer's Solution to Enhance Lactate Clearance in Septic Patients After Initial Resuscitation in the ED: A Retrospective Cohort Trial. [2022]
A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis. [2023]
Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study. [2020]
[Efficacy of Lactated Ringer's versus Normal Saline in Treating Patients with Septic Shock]. [2019]
0.9% NaCl (Normal Saline) - Perhaps not so normal after all? [2019]
A Hospital-Wide Open-Label Cluster Crossover Pragmatic Comparative Effectiveness Randomized Trial Comparing Normal Saline to Ringer's Lactate: Protocol and Statistical Analysis Plan of The FLUID Trial. [2023]
Changes in serum electrolyte and atrial natriuretic peptide concentrations, acid-base and haemodynamic status after rapid infusion of isotonic saline and Ringer lactate solution in healthy volunteers. [2019]
Assessment of renal hemodynamic toxicity of fluid challenge with 0.9% NaCl compared to balanced crystalloid (PlasmaLyte®) in a rat model with severe sepsis. [2020]
A brief history of crystalloids: the origin of the controversy. [2023]
A multicentre randomised controlled pilot study of fluid resuscitation with saline or Plasma-Lyte 148 in critically ill patients. [2022]