Fluids in Septic Shock (FISSH)

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Sepsis, Septic Shock

Intervention / Treatment
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* Other: higher chloride crystalloid
* Other: lower chloride crystalloid


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day Mortality | 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 | Development of stage 2 or worse acute kidney injury (AKI) according to KIDGO guidelines on serum creatinine criteria | up to 30 days |