Clinical trial NCT02748382: Fluids in Sepsis and Septic Shock
Official title: Fluids in Sepsis and Septic Shock: A Pilot Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Sepsis
Septic Shock
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Hamilton Health Sciences Corporation
First posted: 2016-04-22
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Consent Rate
timeFrame: 12 months
measure: Patient Recruitment
timeFrame: 12 months
measure: Protocol Adherence
timeFrame: 12 months
Secondary outcomes:
measure: Hospital length of stay
timeFrame: Duration of index hospital stay censored at 90 days.
measure: Hospital mortality
timeFrame: hospital stay or up to 90 days
measure: Renal replacement therapy use
timeFrame: RRT use during index hospital stay censored at 90 days.
measure: ICU length of stay
timeFrame: Duration of index ICU stay censored at 90 days.
measure: Hyperkalemia
timeFrame: Incidence during index ICU stay or up to 30 days
measure: Acidosis
timeFrame: Incidence during index ICU stay or up to 30 days
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Juravinski Hospital-Hamilton Health Sciences
state: Ontario
city: Sherbrooke
country: Canada
facility: Centre Hospitalier Universitaire de Sherbrooke
state: Quebec
Study officials:
References:
citation: 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.