Clinical trial NCT03677102: Fluids in Septic Shock (FISSH)
Official title: Fluids in Septic Shock (FISSH): a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Sepsis, Septic Shock
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: The Physicians' Services Incorporated Foundation
name: Canadian Institutes of Health Research (CIHR)
First posted: 2018-09-19
Enrollment: 1096
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 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: 30-day Mortality
timeFrame: up to 30 days
Secondary outcomes:
measure: Acute Kidney Injury
timeFrame: up to 30 days
Other outcomes:
measure: Hospital/ICU length of stay
timeFrame: up to 30 days
measure: Ventilator free days
timeFrame: censored at 30 days
measure: Number of days requiring vasoactive agents
timeFrame: up to 30 days
measure: Incidence of biochemical abnormalities during study period
timeFrame: up to 30 days
Locations:
city: Calgary
country: Canada
facility: University of Calgary - Foothills Medical Centre
state: Alberta
city: Calgary
country: Canada
facility: University of Calgary - Rockyview General Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Grey Nuns Community Hospital
state: Alberta
city: Halifax
country: Canada
facility: Halifax Infirmary
state: Nova Scotia
city: Halifax
country: Canada
facility: Victoria General
state: Nova Scotia
city: Sydney
country: Canada
facility: Cape Breton Regional Hospital
state: Nova Scotia
city: Ajax
country: Canada
facility: Lakeridge Health - Ajax Pickering
state: Ontario
city: Brantford
country: Canada
facility: Brantford General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St Joseph's Healthcare
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital-Hamilton Health Sciences
state: Ontario
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre - Victoria Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences - University Hospital
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health
state: Ontario
city: St Catharines
country: Canada
facility: Niagara Health, St Catharines Site
state: Ontario
city: Toronto
country: Canada
facility: Unity Health (St. Michael's Hospital)
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital - Ouellette Campus
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hospital -Metropolitan Campus
state: Ontario
city: Montreal
country: Canada
facility: Centre intégré Universitaire de santé et de services sociaux du Nord de l'île de Montréal
state: Quebec
city: Montréal
country: Canada
facility: Centre Hospitalier de l'Universite de Montreal (CHUM)
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de recherche du CIUSSS de l'Estrie - CHUS de Sherbrooke
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre intégré universitaire de santé et de services sociaux de la Mauricie-et-du-Centre-du-Québec (CIUSSS MCQ)
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Saskatoon
country: Canada
facility: St Paul's Hospital
state: Saskatchewan
city: Riyadh
country: Saudi Arabia
facility: King Abdulaziz Medical City- Riyadh (KAMC-R)
city: Riyadh
country: Saudi Arabia
facility: King Faisal Specialist Hospital & Research Centre
Study officials:
affiliation: McMaster University
name: Bram Rochwerg, MSc,MD,FRCPC
role: PRINCIPAL_INVESTIGATOR
References: