Crystalloid Solutions for Septic Shock
(FISSH Trial)
Recruiting in Palo Alto (17 mi)
+29 other locations
Overseen byBram Rochwerg, MSc,MD,FRCPC
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: McMaster University
Disqualifiers: Intracranial bleed, Acute burn, ESRD, others
No Placebo Group
Prior Safety Data
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?
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?
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
Trial 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 (Crystalloid Solution)
- Lower Chloride Crystalloid (Crystalloid Solution)
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
Research Locations NearbySelect from list below to view details:
Hôpital Maisonneuve RosemontMontréal, Canada
Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)Trois-Rivières, Canada
Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de MontréalMontreal, Canada
Centre de recherche du CIUSSS de l'Estrie - CHUS de SherbrookeSherbrooke, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
McMaster UniversityLead Sponsor
The Physicians' Services Incorporated FoundationCollaborator
Canadian Institutes of Health Research (CIHR)Collaborator
References
Effect of Early Balanced Crystalloids Before ICU Admission on Sepsis Outcomes. [2022]Studies suggest that using balanced crystalloids (lactated Ringer's solution or Plasma-Lyte A) rather than saline (0.9% sodium chloride) may improve outcomes for patients with sepsis in the ED and ICU.
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]To compare the effect of isotonic crystalloid solutions between lactated Ringer's solution (LRS) and normal saline solution (NSS) on lactate clearance in septic patients at the emergency department (ED).
A retrospective analysis of normal saline and lactated ringers as resuscitation fluid in sepsis. [2023]The Surviving Sepsis Campaign suggested preferential resuscitation with balanced crystalloids, such as Lactated Ringer's (LR), although the level of recommendation was weak, and the quality of evidence was low. Past studies reported an association of unbalanced solutions, such as normal saline (NS), with increased AKI risks, metabolic acidosis, and prolonged ICU stay, although some of the findings are conflicting. We have compared the outcomes with the preferential use of normal saline vs. ringer's lactate in a cohort of sepsis patients.
Pragmatic Pediatric Trial of Balanced Versus Normal Saline Fluid in Sepsis: The PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study. [2020]Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock.
[Efficacy of Lactated Ringer's versus Normal Saline in Treating Patients with Septic Shock]. [2019]Objective To compare the clinical efficacy of lactated Ringer's (LR) and normal saline (NS) in treating patients with septic shock. Methods The clinical data of 198 patients with septic shock who received fluid resuscitation in the Intensive Care Unit of Quzhou People's Hospital from January 2014 to January 2016 were retrospectively analyzed. These patients were divided into NS group (n=100) and LR group (n=98) according to fluids used. The amounts of trial fluid,other liquids,and blood products and the average total fluid volume were recorded. The oxygenation index (PO2/FiO2),mean artery pressure (MAP),central venous pressure (CVP),and B-type natriuretic peptide (BNP) before and after treatment as well as the early goal-directed therapy (EGDT) 8 h (EGDT8),EGDT 24 h recovery rate,EGDT recovery time,28-day mortality rate were compared. Other secondary outcomes including bleeding,allergic reaction,acute kidney injury (AKI),venous blood filtration (RRT) rate,hyperkalemia,and ICU stay were also recorded. The 28-day survival rate was calculated using the Kaplan-Maier method,and the difference in survival rate was compared by log-rank test. Results The two groups showed no significant difference in gender,age,body weight,source of admission to ICU,procalcitonin level,source of sepsis,Acute Physiology and Chronic Health Evaluation Ⅱ score,number of AKI patients,amount of white blood cells,and C-reactive protein level (all P>0.05). The amount of blood products on the first day [(782±357)ml vs.(606±273)ml;t=2.044,P=0.046] and the average total amount of liquid on the first three days [(5470±1078)ml vs.(5092±929) ml;t=2.640,P=0.009] were significantly higher in NS group than in LR group. The amount of trial fluid and the volumes of other fluids were not significantly different (both P>0.05). The PO2/FiO2,MAP,CVP,and BNP levels significantly increased after treatment in both groups (all P<0.05);however,they were not significantly different between LR group and NS group at different time points before and after treatment (all P>0.05). The incidences of hyperlactacidemia (86.0% vs.71.4%,OR:2.457,95%CI:1.202-5.023,P=0.012) and hyperchloremia (25.0% vs.13.2%,OR:2.179,95%CI:1.041-4.562,P=0.036) were significantly higher in NS group than in LR group. These two groups showed no significant difference in EGDT8,24 h recovery rate,EGDT recovery time,28-day mortality rate,AKI,RRT rate,hyperkalemia,and ICU stay (all P>0.05). Kaplan-Meier survival analysis showed that the 28-day survival rate was not significantly different (χ2 log-rank=0.012,P=0.911). Conclusion When liquid resuscitation is applied in patients with septic shock,the use of LR can lower blood transfusion requirement on the first day and total liquid dosage on the first three days (compared with NR), along with lower incidences of hyperlactacidemia and hyperchloremia,although there was no significant difference in the 28-day mortality rate.
0.9% NaCl (Normal Saline) - Perhaps not so normal after all? [2019]Crystalloid infusion is widely employed in patient care for volume replacement and resuscitation. In the United States the crystalloid of choice is often normal saline. Surgeons and anesthesiologists have long preferred buffered solutions such as Ringer's Lactate and Plasma-Lyte A. Normal saline is the solution most widely employed in medical and pediatric care, as well as in hematology and transfusion medicine. However, there is growing concern that normal saline is more toxic than balanced, buffered crystalloids such as Plasma-Lyte and Lactated Ringer's. Normal saline is the only solution recommended for red cell washing, administration and salvage in the USA, but Plasma-Lyte A is also FDA approved for these purposes. Lactated Ringer's has been traditionally avoided in these applications due to concerns over clotting, but existing research suggests this is not likely a problem. In animal models and clinical studies in various settings, normal saline can cause metabolic acidosis, vascular and renal function changes, as well as abdominal pain in comparison with balanced crystalloids. The one extant randomized trial suggests that in very small volumes (2 l or less) normal saline is not more toxic than other crystalloids. Recent evidence suggests that normal saline causes substantially more in vitro hemolysis than Plasma-Lyte A and similar solutions during short term storage (24 hours) after washing or intraoperative salvage. There are now abundant data to raise concerns as to whether normal saline is the safest replacement solution in infusion therapy, red cell washing and salvage, apheresis and similar uses. In the USA, Plasma-Lyte A is also FDA approved for use with blood components and is likely a safer solution for these purposes. Its only disadvantage is a higher cost. Additional studies of the safety of normal saline for virtually all current clinical uses are needed. It seems likely that normal saline will eventually be abandoned in favor of safer, more physiologic crystalloid solutions in the coming years.
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]Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids given to hospitalized patients. Despite concern about possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function, and death), few large multicenter randomized trials focused on critically ill patients have compared these fluids. Uncertainty exists about the effects of these fluids on clinically important outcomes across all hospitalized patients.
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]Opinions differ on the use of isotonic sodium chloride and Ringer lactate solution for extracellular volume depletion. We have compared changes in serum electrolyte concentrations and acid-base and haemodynamic status after rapid infusion of 2 litre of either isotonic sodium chloride or Ringer lactate solution in healthy volunteers. Changes within groups were small and statistically insignificant. Central venous pressure changes were associated with secretion of atrial natriuretic peptide, but this response was delayed.
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]Label="BACKGROUND" NlmCategory="BACKGROUND">According to international guidelines, volume expansion with crystalloids is the first-line treatment for hemodynamic management in patients with severe sepsis or septic shock. Compared to balanced crystalloids, 0.9% sodium chloride (0.9% NaCl) induces hyperchloremia and metabolic acidosis and may alter renal hemodynamics and function. We compared the effects of 0.9% NaCl to a less chloride-concentrated fluid, PlasmaLyte® (PL) in targeted fluid resuscitation in a randomized, double-blind controlled study in an experimental model of severe sepsis in rats.
A brief history of crystalloids: the origin of the controversy. [2023]Fluid resuscitation with crystalloids has been used in humans for more than 100 years. In patients with trauma, sepsis or shock of any etiology, they can help modify the clinical course of the illness. However, these solutions are medications which are not side-effect free. Recently, they have been questioned in terms of quantity (fluid overload) and their composition. The most frequently used crystalloids, both in high and low-income countries, are 0.9% normal saline (NS) and Ringer's lactate. The first descriptions of the use of sodium and water solutions in humans date from the cholera epidemic which spread throughout Europe in 1831. The composition of the fluids used by medical pioneers at that time differs greatly from the 0.9% NS used routinely today. The term "physiological solution" referred to fluids which did not cause red blood cell hemolysis in amphibians in in vitro studies years later. 0.9% NS has an acid pH, a more than 40% higher chloride concentration than plasma and a strong ion difference of zero, leading many researchers to consider it an unbalanced solution. In many observational studies and clinical trials, this 0.9% NS composition has been associated with multiple microcirculation and immune response complications, acute kidney injury, and worse clinical outcomes. Ringer's lactate has less sodium than plasma, as well as other electrolytes which can cause problems in patients with traumatic brain injury. This review provides a brief summary of the most important historical aspects of the origin of the most frequently used intravenous crystalloids today.
A multicentre randomised controlled pilot study of fluid resuscitation with saline or Plasma-Lyte 148 in critically ill patients. [2022]Normal saline (NS) is the most commonly used crystalloid solution worldwide but contains an excess of chloride and may cause metabolic acidosis and hyperchloraemia. Such abnormalities may be attenuated by the use of a balanced solution such as Plasma-Lyte 148 (PL-148).