Fluids in Sepsis and Septic Shock (FISSH)

Fluids in Sepsis and Septic Shock: A Pilot 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 RCT evidence. Editorials published in leading critical care journals have called for RCT's to address this important clinical question. The proposed feasibility RCT will investigate the feasibility of a large-scale trial directly comparing low chloride versus normal chloride for resuscitation in septic shock on patient-important outcomes such as mortality and AKI.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock
• Intervention / Treatment: Other: higher chloride crystalloid; Other: higher chloride albumin; Other: lower chloride crystalloid; Other: lower chloride albumin

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 taht 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). Although, the investigators plan for a larger trial looking at patient-important outcomes such as rate of death, kidney failure and length of stay in the ICU the investigators think it's important to start with a feasibility study. If the investigators are able to show a larger trial is feasible then the investigators will apply for further funding and use the lessons learned from this pilot to optimize the larger study. The larger study has the potential to guide the care of critically ill patients with infection worldwide.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C1
      • Juravinski Hospital-Hamilton Health Sciences
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 3H5
      • Centre Hospitalier Universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient must be at least 16 years of age
2. Within 6 hours from presentation to hospital or activation of MET/RACE team to ward

3. Requires fluid resuscitation for refractory hypotension OR organ hypoperfusion

   • refractory hypotension definition - sBP <90 OR MAP <65 after 1L bolus given over 1 hour or less
   • organ hypoperfusion - lactate >4
4. Suspected source of infection as etiology for hypotension
5. Treating physician anticipates patient will require admission to ICU

Exclusion Criteria:

1. Intracranial bleed or intracranial hypertension during this hospital admission
2. Acute burn injury (>10% body surface area)
3. Bleeding/hemorrhage as likely cause of hypotension
4. Plan in place to change goals of care to palliation
5. Previously enrolled in FISSH
6. Previously enrolled in confounding trial
7. Transfer from another hospital or facility
8. Admission directly from the operating room or PACU

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: higher chloride solutions; higher chloride crystalloid (Normal saline) higher chloride albumin (5% Octalbin)	Other: higher chloride crystalloid; Normal saline; Other: higher chloride albumin; 5% Octalbin
Active Comparator: lower chloride solutions; lower chloride crystalloid (Ringer's lactate) lower chloride albumin (5% Plasbumin)	Other: lower chloride crystalloid; Ringers Lactate; Other: lower chloride albumin; 5% Plasbumin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consent Rate	Consent rate will be considered adequate if greater than 70% of substitute decision makers (SDMs) or patients when approached for consent choose to participate.	12 months
Patient Recruitment	Successful recruitment will be defined as achieving enrolment of 50 patients over the 12-month study period. This works out to approximately 1 patient/center/month. Once the pilot trial begins, the screening logs will be reviewed at all three study centers by the study steering committee on a monthly basis. We will record exclusions and reasons for physician refusals.	12 months
Protocol Adherence	Successful adherence will be defined as patients receiving at least 75% study fluid of all intravenous fluid that is administered in the ICU excluding blood products and medication infusions.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital length of stay		Duration of index hospital stay censored at 90 days.
Hospital mortality	Mortality during index hospitalization censored at 90 days.	hospital stay or up to 90 days
Renal replacement therapy use	Any use of renal replacement therapy including hemodialysis, peritoneal dialysis or continuous renal replacement. This will be reported as a dichotomous outcome.	RRT use during index hospital stay censored at 90 days.
ICU length of stay		Duration of index ICU stay censored at 90 days.
Hyperkalemia	Number of participants with any serum potassium value >5mmol/L.	Incidence during index ICU stay or up to 30 days
Acidosis	Number of participants with any serum pH <7.20	Incidence during index ICU stay or up to 30 days

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Hamilton Health Sciences Corporation

Publications and helpful links

General Publications

• Rochwerg B, Millen T, Austin P, Zeller M, D'Aragon F, Jaeschke R, Masse MH, Mehta S, Lamontagne F, Meade M, Guyatt G, Cook DJ; Canadian Critical Care Trials Group. Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial. BMJ Open. 2017 Jul 20;7(7):e017602. doi: 10.1136/bmjopen-2017-017602.

Study record dates

Study Major Dates

• Study Start (Actual): August 18, 2016
• Primary Completion (Actual): August 19, 2017
• Study Completion (Actual): August 19, 2017

Study Registration Dates

• First Submitted: April 8, 2016
• First Submitted That Met QC Criteria: April 19, 2016
• First Posted (Estimate): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 27, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Shock, Septic; Shock
• Other Study ID Numbers: 1636

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No