Fluids in Septic Shock (FISSH)

Sepsis, Septic Shock Clinical Trial

— FISSH  

Official title:

Fluids in Septic Shock (FISSH): a Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03677102
• Other study ID #: 1515
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 9, 2018
• Est. completion date: March 31, 2026

Study information

• Verified date: March 2024
• Source: McMaster University
• Contact: Bram Rochwerg, MSc,MD,FRCPC
• Phone: 905-521-2100
• Email: rochwerg[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Despite evidence of the physiologic benefits and possible lower mortality associated with low chloride solutions, normal saline remains the most wildly used fluid in the world. Given uncertainty about the impact of lower chloride versus higher chloride solutions on mortality, it is unlikely that clinical practice will change without new and direct randomized controlled trial (RCT) evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. This trial will directly compare low chloride versus normal chloride for resuscitation in septic shock on patient-important outcomes such as mortality and AKI.

Description:

Severe infection can lead to many complications within the human body including low blood pressure, which is called septic shock. The main treatments for septic shock are intravenous antibiotics and intravenous fluid. There are many different intravenous fluids available for doctors to use. Each one of these fluids has potential advantages as well as potential disadvantages. Doctors will often look at many things when deciding which fluid to give including the results of bloodwork and the clinical characteristics of the patients themselves. There is limited direction from research studies that using one fluid type is better than another. Some preliminary research in the field has suggested that one specific electrolyte, call chloride, may be harmful when given to patients in high concentrations. Animal research has shown that the administration of high chloride fluids may be harmful to the lungs, kidneys, gastrointestinal and muscle cells. Some intravenous fluids have higher concentrations of chloride than others. The investigators plan to study the impact of giving patients with severe infection intravenous fluids with either a high chloride concentration (normal saline or high chloride albumin) or a low chloride concentration (Ringers Lactate or low chloride albumin). This trial will build on the earlier pilot, phase 1 study and will look at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU. This larger study has the potential to guide the care of critically ill patients with infection worldwide.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1096
• Est. completion date: March 31, 2026
• Est. primary completion date: November 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• patients 16 years or greater who meet all of the following:
• require fluid resuscitation for refractory hypotension (systolic blood pressure <90 mmHg or mean arterial blood pressure<65 mmHg after 1 Litre bolus over 1 hour or less or organ hypo-perfusion (serum lactate >4 mmol/L)
• have a clinical suspicion of infection
• are within 6 hours of hospital admission or critical care response team consultation
• are anticipated to require ICU admission

Exclusion Criteria:

• intracranial bleed or intracranial hypertension during the index hospital admission
• 10% of body surface area acute burn injury
• bleeding/hemorrhage as likely cause of hypotension
• a lack of commitment to life support
• have previously enrolled in FISSH, or a confounding trial (e.g. a trial examining the effect of other intravenous fluids in septic shock patients)
• been transferred from another hospital or facility >6 hours since presentation to first hospital
• pre-established end stage renal disease (ESRD) or are receiving hemodialysis (intermittent or continuous) at time of enrolment, or
• been admitted to ICU directly from the operating room or post anaesthetic care unit

Related Conditions & MeSH terms

• Sepsis, Septic Shock
• Shock
• Shock, Septic

Intervention

Other:
• higher chloride crystalloid
Normal saline (chloride concentration 154 mmol/L)
• lower chloride crystalloid
Ringer's Lactate (chloride concentration 110 mmol/L)

Locations

Country	Name	City	State
Canada	Brantford General Hospital	Brantford	Ontario
Canada	University of Calgary - Foothills Medical Centre	Calgary	Alberta
Canada	University of Calgary - Rockyview General Hospital	Calgary	Alberta
Canada	Grey Nuns Community Hospital	Edmonton	Alberta
Canada	Halifax Infirmary	Halifax	Nova Scotia
Canada	Victoria General	Halifax	Nova Scotia
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Juravinski Hospital-Hamilton Health Sciences	Hamilton	Ontario
Canada	St Joseph's Healthcare	Hamilton	Ontario
Canada	Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences - University Hospital	London	Ontario
Canada	London Health Sciences Centre - Victoria Hospital	London	Ontario
Canada	Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal	Montreal	Quebec
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montréal	Quebec
Canada	Lakeridge Health	Oshawa	Ontario
Canada	Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke	Sherbrooke	Quebec
Canada	Niagara Health, St Catharines Site	St Catharines	Ontario
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Unity Health (St. Michael's Hospital)	Toronto	Ontario
Canada	Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)	Trois-Rivières	Quebec
Saudi Arabia	King Abdulaziz Medical City- Riyadh (KAMC-R)	Riyadh
Saudi Arabia	King Faisal Specialist Hospital & Research Centre	Riyadh

Sponsors (3)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), The Physicians' Services Incorporated Foundation

Countries where clinical trial is conducted

Canada,  Saudi Arabia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hospital/ICU length of stay	length of hospital/ICU stay up to 30 days	up to 30 days
Other	Ventilator free days	Number of ventilator free days	censored at 30 days
Other	Number of days requiring vasoactive agents	defined as the number of days requiring great than or equal to 2 hours of intravenous vasopressor support	up to 30 days
Other	Incidence of biochemical abnormalities during study period	any serum blood test results showing hyperchloremia, hyperkalemia, hypernatremia, or acidosis	up to 30 days
Primary	30-day Mortality	We expect that if a difference in survival is demonstrated, that this will be evident within 30 days	up to 30 days
Secondary	Acute Kidney Injury	Development of stage 2 or worse acute kidney injury (AKI) according to KIDGO guidelines on serum creatinine criteria	up to 30 days