Fluids in Septic Shock (FISSH) (FISSH)

March 6, 2024 updated by: McMaster University

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

1096

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Peggy Austin
  • Phone Number: 22154 905-525-9140
  • Email: austinp@hhsc.ca

Study Contact Backup

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
        • Recruiting
        • University of Calgary - Foothills Medical Centre
        • Contact:
        • Principal Investigator:
          • Ken Parhar, MD MSc FRCPC
      • Calgary, Alberta, Canada
        • Recruiting
        • University of Calgary - Rockyview General Hospital
        • Contact:
        • Principal Investigator:
          • Ken Parhar, MD MSc FRCPC
      • Edmonton, Alberta, Canada
        • Recruiting
        • Grey Nuns Community Hospital
        • Contact:
        • Principal Investigator:
          • Janek Senaratne, MD,MSc,ABIM,FRCPC,FACC,FESC
        • Sub-Investigator:
          • Lazar Milovanovic, MD,FRCPC
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
        • Recruiting
        • Halifax Infirmary
        • Contact:
        • Principal Investigator:
          • Osama Loubani, MD,FRCPC,DABEM
        • Sub-Investigator:
          • Stephen Beed, MD, FRCPC
        • Sub-Investigator:
          • Volker Eichhorn, MD
        • Sub-Investigator:
          • Robert Green, MD, FRCPC
        • Sub-Investigator:
          • Jennifer Hancock, MD, FRCP
        • Sub-Investigator:
          • Babar Haroon, MD, FRCPC
        • Sub-Investigator:
          • Sarah McMullen, MD, FRCPC
        • Sub-Investigator:
          • Samuel Minor, MD, FRCSC
        • Sub-Investigator:
          • Laurel Murphy, MD, FRCPC
        • Sub-Investigator:
          • Tony O'Leary, MD, FRCP
        • Sub-Investigator:
          • Patrick Ward, MD, FRCP
        • Sub-Investigator:
          • Jack Rasmussen, MD, FRCSC
        • Sub-Investigator:
          • Edmund Chong-How (Edmund) Tan, MD, FRCPC
        • Sub-Investigator:
          • Tobias Witter, MD
      • Halifax, Nova Scotia, Canada
        • Recruiting
        • Victoria General
        • Principal Investigator:
          • Osama Loubani, MD,FRCPC,DABEM
        • Contact:
        • Sub-Investigator:
          • Stephen Beed, MD, FRCPC
        • Sub-Investigator:
          • Volker Eichhorn, MD
        • Sub-Investigator:
          • Robert Green, MD, FRCPC
        • Sub-Investigator:
          • Jennifer Hancock, MD, FRCP
        • Sub-Investigator:
          • Babar Haroon, MD, FRCPC
        • Sub-Investigator:
          • Sarah McMullen, MD, FRCPC
        • Sub-Investigator:
          • Samuel Minor, MD, FRCSC
        • Sub-Investigator:
          • Laurel Murphy, MD, FRCPC
        • Sub-Investigator:
          • Tony O'Leary, MD, FRCP
        • Sub-Investigator:
          • Patrick Ward, MD, FRCP
        • Sub-Investigator:
          • Jack Rasmussen, MD, FRCSC
        • Sub-Investigator:
          • Tobias Witter, MD
        • Sub-Investigator:
          • Edmund Chong-How (Edmund) Tanter, MD, FRCPC
    • Ontario
      • Brantford, Ontario, Canada, N3R 1G9
        • Recruiting
        • Brantford General Hospital
        • Contact:
        • Principal Investigator:
          • Brenda Reeve, MD, FRCPC
      • Hamilton, Ontario, Canada
        • Recruiting
        • Hamilton General Hospital
        • Contact:
        • Principal Investigator:
          • Maureen Meade, MD,FRCPC,MSc
      • Hamilton, Ontario, Canada, L8N 4A6
        • Recruiting
        • St Joseph's Healthcare
        • Contact:
        • Principal Investigator:
          • Deborah J Cook, MD,FRCPC,MSc
      • Hamilton, Ontario, Canada, L8V 1C1
        • Recruiting
        • Juravinski Hospital-Hamilton Health Sciences
        • Contact:
        • Principal Investigator:
          • Bram Rochwerg, MSc,MD,FRCPC
        • Contact:
      • Kingston, Ontario, Canada, K7L 2V7
        • Recruiting
        • Kingston General Hospital
        • Contact:
        • Principal Investigator:
          • Gordon Boyd, MD,PhD,FRCPC
      • London, Ontario, Canada, N6A 5W9
        • Recruiting
        • London Health Sciences Centre - Victoria Hospital
        • Contact:
        • Principal Investigator:
          • Ian Ball, MC,MSc,FRCPC
        • Sub-Investigator:
          • Marat Slessarev, MD, FRCPC
      • London, Ontario, Canada
        • Recruiting
        • London Health Sciences - University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ian Ball, MD,MSc(Epi),FRCPC
        • Sub-Investigator:
          • John Basmaji, MD,FRCPC
      • Oshawa, Ontario, Canada, L1G 2B9
        • Recruiting
        • Lakeridge Health
        • Contact:
        • Contact:
        • Principal Investigator:
          • Shannon Fernando, MD,MSc,FRCPC
        • Sub-Investigator:
          • Karim Soliman, MD,FRCPC
        • Sub-Investigator:
          • Kavita Sridhar, MD,MHSc,FRCPC
      • St Catharines, Ontario, Canada, L2S 0A9
        • Recruiting
        • Niagara Health, St Catharines Site
        • Contact:
        • Principal Investigator:
          • Erick Duan, MD, FRCPC
        • Sub-Investigator:
          • Jennifer Tsang, MD,PhD,FRCPC
      • Toronto, Ontario, Canada, M5G 1X5
        • Recruiting
        • Mount Sinai Hospital
        • Contact:
        • Principal Investigator:
          • SANGEETA MEHTA, MD,FRCPC
      • Toronto, Ontario, Canada
        • Recruiting
        • Sunnybrook Health Sciences Centre
        • Contact:
        • Principal Investigator:
          • Neill Adhikari, MDCM, MSc.
      • Toronto, Ontario, Canada, M5B 1W8
        • Recruiting
        • Unity Health (St. Michael's Hospital)
        • Contact:
        • Principal Investigator:
          • Karen E Burns, MD,FRCPC
        • Sub-Investigator:
          • Jan Friedrich, MD, PhD, MSc
    • Quebec
      • Montreal, Quebec, Canada, H4J 1C5
        • Recruiting
        • Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal
        • Contact:
        • Principal Investigator:
          • Karim Serri, BSc,MD
      • Montréal, Quebec, Canada
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Recruiting
        • Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke
        • Contact:
        • Principal Investigator:
          • François Lamontagne, MD,MSc
        • Sub-Investigator:
          • Fred D'aragon, MD, MSc
      • Trois-Rivières, Quebec, Canada
        • Recruiting
        • Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)
        • Contact:
        • Principal Investigator:
          • Jean-Francois Naud, MD
  • Saudi Arabia
      • Riyadh, Saudi Arabia
        • Recruiting
        • King Faisal Specialist Hospital & Research Centre
        • Contact:
        • Principal Investigator:
          • Zainab Al Duhailib, MD
      • Riyadh, Saudi Arabia
        • Recruiting
        • King Abdulaziz Medical City- Riyadh (KAMC-R)
        • Contact:
          • Felwa Bin Humaid, BSc
        • Principal Investigator:
          • Sara Aldekhyl, MBBS,ABIM,FRCPc,MedEd

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: higher chloride solutions
higher chloride crystalloid (Normal saline - chloride concentration 154 mmol/L)
Other: higher chloride crystalloid
Normal saline (chloride concentration 154 mmol/L)
Active Comparator: lower chloride solutions
lower chloride crystalloid (Ringer's lactate - chloride concentration 110 mmol/L)
Other: lower chloride crystalloid
Ringer's Lactate (chloride concentration 110 mmol/L)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
30-day Mortality
Time Frame: up to 30 days
We expect that if a difference in survival is demonstrated, that this will be evident within 30 days
up to 30 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acute Kidney Injury
Time Frame: up to 30 days
Development of stage 2 or worse acute kidney injury (AKI) according to KIDGO guidelines on serum creatinine criteria
up to 30 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hospital/ICU length of stay
Time Frame: up to 30 days
length of hospital/ICU stay up to 30 days
up to 30 days
Ventilator free days
Time Frame: censored at 30 days
Number of ventilator free days
censored at 30 days
Number of days requiring vasoactive agents
Time Frame: up to 30 days
defined as the number of days requiring great than or equal to 2 hours of intravenous vasopressor support
up to 30 days
Incidence of biochemical abnormalities during study period
Time Frame: up to 30 days
any serum blood test results showing hyperchloremia, hyperkalemia, hypernatremia, or acidosis
up to 30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Collaborators

Canadian Institutes of Health Research (CIHR)
The Physicians' Services Incorporated Foundation

Investigators

  • Principal Investigator: Bram Rochwerg, MSc,MD,FRCPC, McMaster University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 9, 2018

Primary Completion (Estimated)

November 28, 2025

Study Completion (Estimated)

March 31, 2026

Study Registration Dates

First Submitted

August 27, 2018

First Submitted That Met QC Criteria

September 17, 2018

First Posted (Actual)

September 19, 2018

Study Record Updates

Last Update Posted (Actual)

March 7, 2024

Last Update Submitted That Met QC Criteria

March 6, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1515

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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