Fluids in Septic Shock (FISSH)

Last updated: February 25, 2026
Sponsor: McMaster University
Overall Status: Completed

Phase

2/3

Condition

Low Blood Pressure (Hypotension)

Soft Tissue Infections

Treatment

higher chloride crystalloid

lower chloride crystalloid

Clinical Study ID

NCT03677102
1515
  • Ages > 16
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • patients 16 years or greater who meet all of the following:

  • require fluid resuscitation for refractory hypotension (systolic blood pressure <90mmHg or mean arterial blood pressure<65 mmHg after 1 Litre bolus over 1 hour or lessor 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

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 examiningthe effect of other intravenous fluids in septic shock patients)

  • been transferred from another hospital or facility >6 hours since presentation tofirst 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

Study Design

Total Participants: 1113
Treatment Group(s): 2
Primary Treatment: higher chloride crystalloid
Phase: 2/3
Study Start date:
September 09, 2018
Estimated Completion Date:
February 10, 2026

Study 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.

Connect with a study center

  • Foothills Medical Centre

    Calgary, Alberta
    Canada

    Active - Recruiting

  • Rockyview General Hospital

    Calgary, Alberta
    Canada

    Active - Recruiting

  • University of Calgary - Foothills Medical Centre

    Calgary, Alberta
    Canada

    Site Not Available

  • University of Calgary - Rockyview General Hospital

    Calgary, Alberta
    Canada

    Active - Recruiting

  • Covenant Health

    Edmonton, Alberta
    Canada

    Active - Recruiting

  • Covenant Health-Grey Nuns Community Hospital

    Edmonton, Alberta
    Canada

    Active - Recruiting

  • Grey Nuns Community Hospital

    Edmonton, Alberta
    Canada

    Site Not Available

  • University of Calgary - Foothills Medical Centre

    Calgary 5913490, Alberta 5883102
    Canada

    Site Not Available

  • University of Calgary - Rockyview General Hospital

    Calgary 5913490, Alberta 5883102
    Canada

    Site Not Available

  • Grey Nuns Community Hospital

    Edmonton 5946768, Alberta 5883102
    Canada

    Site Not Available

  • Halifax Infirmary

    Halifax, Nova Scotia
    Canada

    Site Not Available

  • Victoria General

    Halifax, Nova Scotia
    Canada

    Active - Recruiting

  • Cape Breton Regional Hospital

    Sydney, Nova Scotia
    Canada

    Site Not Available

  • Halifax Infirmary

    Halifax 6324729, Nova Scotia 6091530
    Canada

    Site Not Available

  • Victoria General

    Halifax 6324729, Nova Scotia 6091530
    Canada

    Site Not Available

  • Cape Breton Regional Hospital

    Sydney 6354908, Nova Scotia 6091530
    Canada

    Site Not Available

  • Lakeridge Health - Ajax Pickering

    Ajax, Ontario
    Canada

    Site Not Available

  • Brantford General Hospital

    Brantford, Ontario N3R 1G9
    Canada

    Site Not Available

  • Hamilton General Hospital

    Hamilton, Ontario
    Canada

    Active - Recruiting

  • Juravinski Hospital-Hamilton Health Sciences

    Hamilton, Ontario L8V 1C1
    Canada

    Active - Recruiting

  • St Joseph's Healthcare

    Hamilton, Ontario L8N 4A6
    Canada

    Site Not Available

  • Kingston General Hospital

    Kingston, Ontario K7L 2V7
    Canada

    Site Not Available

  • London Health Sciences - University Hospital

    London, Ontario
    Canada

    Site Not Available

  • London Health Sciences Centre - Victoria Hospital

    London, Ontario N6A 5W9
    Canada

    Active - Recruiting

  • Lakeridge Health

    Oshawa, Ontario L1G 2B9
    Canada

    Site Not Available

  • Niagara Health, St Catharines Site

    St Catharines, Ontario L2S 0A9
    Canada

    Site Not Available

  • Mount Sinai Hospital

    Toronto, Ontario M5G 1X5
    Canada

    Active - Recruiting

  • St. Michael's Hospital

    Toronto, Ontario M5B 1W8
    Canada

    Active - Recruiting

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario
    Canada

    Site Not Available

  • Sunnybrook Helath Sciences Centre

    Toronto, Ontario
    Canada

    Active - Recruiting

  • Unity Health (St. Michael's Hospital)

    Toronto, Ontario M5B 1W8
    Canada

    Active - Recruiting

  • Windsor Regional Hospital - Ouellette Campus

    Windsor, Ontario
    Canada

    Active - Recruiting

  • Windsor Regional Hospital -Metropolitan Campus

    Windsor, Ontario
    Canada

    Site Not Available

  • Lakeridge Health - Ajax Pickering

    Ajax 5882873, Ontario 6093943
    Canada

    Site Not Available

  • Brantford General Hospital

    Brantford 5907990, Ontario 6093943 N3R 1G9
    Canada

    Site Not Available

  • Hamilton General Hospital

    Hamilton 5969782, Ontario 6093943
    Canada

    Site Not Available

  • Juravinski Hospital-Hamilton Health Sciences

    Hamilton 5969782, Ontario 6093943 L8V 1C1
    Canada

    Site Not Available

  • St Joseph's Healthcare

    Hamilton 5969782, Ontario 6093943 L8N 4A6
    Canada

    Site Not Available

  • Kingston General Hospital

    Kingston 5992500, Ontario 6093943 K7L 2V7
    Canada

    Site Not Available

  • London Health Sciences - University Hospital

    London 6058560, Ontario 6093943
    Canada

    Site Not Available

  • London Health Sciences Centre - Victoria Hospital

    London 6058560, Ontario 6093943 N6A 5W9
    Canada

    Site Not Available

  • Lakeridge Health

    Oshawa 6094578, Ontario 6093943 L1G 2B9
    Canada

    Site Not Available

  • Niagara Health, St Catharines Site

    St. Catharines 6155721, Ontario 6093943 L2S 0A9
    Canada

    Site Not Available

  • Mount Sinai Hospital

    Toronto 6167865, Ontario 6093943 M5G 1X5
    Canada

    Site Not Available

  • Sunnybrook Health Sciences Centre

    Toronto 6167865, Ontario 6093943
    Canada

    Site Not Available

  • Unity Health (St. Michael's Hospital)

    Toronto 6167865, Ontario 6093943 M5B 1W8
    Canada

    Site Not Available

  • Windsor Regional Hospital - Ouellette Campus

    Windsor 6182962, Ontario 6093943
    Canada

    Site Not Available

  • Windsor Regional Hospital -Metropolitan Campus

    Windsor 6182962, Ontario 6093943
    Canada

    Site Not Available

  • Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal

    Montreal, Quebec H4J 1C5
    Canada

    Site Not Available

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montréal, Quebec
    Canada

    Site Not Available

  • Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke

    Sherbrooke, Quebec J1H 5N4
    Canada

    Site Not Available

  • Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)

    Trois-Rivières, Quebec
    Canada

    Site Not Available

  • Centre Hospitalier de l'Universite de Montreal (CHUM)

    Montreal 6077243, Quebec 6115047
    Canada

    Site Not Available

  • Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal

    Montreal 6077243, Quebec 6115047 H4J 1C5
    Canada

    Site Not Available

  • CHU de Québec Université Laval

    Québec 6325494, Quebec 6115047 G1J 1Z4
    Canada

    Site Not Available

  • Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke

    Sherbrooke 6146143, Quebec 6115047 J1H 5N4
    Canada

    Site Not Available

  • Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)

    Trois-Rivières 6169141, Quebec 6115047
    Canada

    Site Not Available

  • Royal University Hospital

    Saskatoon, Saskatchewan
    Canada

    Active - Recruiting

  • St Paul's Hospital

    Saskatoon, Saskatchewan
    Canada

    Site Not Available

  • Royal University Hospital

    Saskatoon 6141256, Saskatchewan 6141242
    Canada

    Site Not Available

  • St Paul's Hospital

    Saskatoon 6141256, Saskatchewan 6141242
    Canada

    Site Not Available

  • King Abdulaziz Medical City- Riyadh (KAMC-R)

    Riyadh,
    Saudi Arabia

    Site Not Available

  • King Faisal Specialist Hospital & Research Centre

    Riyadh,
    Saudi Arabia

    Active - Recruiting

  • King Abdulaziz Medical City- Riyadh (KAMC-R)

    Riyadh 108410,
    Saudi Arabia

    Site Not Available

  • King Faisal Specialist Hospital & Research Centre

    Riyadh 108410,
    Saudi Arabia

    Site Not Available

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