Guided Fluid-balance Optimization With Mini-fluid chALlenge During Septic Shock

Study Overview
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Brief Summary
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Many observational studies have highlighted an independent association between fluid overload and clinical outcomes during septic shock. To optimize fluid balance, clinician has several options to consider carefully fluid administration and avoid fluid overload. More than a general restrictive approach, a pragmatic, individual tailored approach should be considered to optimize patients' hemodynamics during acute circulatory failure. Many advances in hemodynamic monitoring were described. Mini-fluid challenge appears to be a sensible method to use for bedside assessment to optimize fluid infusion. The next step for hemodynamic management in the ICU should be to test a hemodynamic goal-directed approach to better control fluid management and eventually improve patient's outcome. The main objective of the GOAL study is to evaluate a pragmatic optimization fluid management protocol tailored to each patient's hemodynamic status based on mini-fluid challenges. This intervention will be compared to usual management based on the latest guidelines. This intervention aims to decrease organ dysfunction during septic shock. This is the first large clinical trial designed to test this hypothesis.

Detailed Description
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GOAL study is a stepped wedge cluster-randomized trial. Centers will switch randomly from the control to the intervention at regular intervals: Control periods: Patients receive a usual optimization fluid management according to surviving sepsis campaign guidelines. Interventional periods: Patients receive a pragmatic, protocolized and individual optimization fluid management according to validated components of a hemodynamic challenges called Mini-Fluid Challenge (MFC). Except fluid therapy in interventional group, management of sepsis will be at the discretion of the attending physician. The use of international guidelines for all therapeutic interventions is recommended in all patients whenever their group. All patients will be followed from enrolment to death or hospital discharge. If alive but not in the hospital after 28 days since septic shock, clinical outcomes will be evaluated by a visit with an intensivist or, if a physical examination is not possible, by a telephone interview performed by an intensivist. To ensure the same data collection in all centers, visits were planned: D0 (inclusion), D1 to D10 (in ICUs), D28 and D180. Classical blinded methods cannot be used in case of evaluation of an optimization protocol. Investigators are unblinded to which arm patient is randomized. To ensure the same evaluation for all patients and in all centers, all events recorded will be evaluated by an independent clinical event committee. All primary endpoints will be analyzed according to a hierarchized analysis to ensure comparison of multiple issues without considering type I error inflation. Secondary outcomes will be analyzed as exploratory analysis.

Official Title
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Guided Fluid-balance Optimization With Mini-fluid chALlenge During Septic Shock: A Multicenter, Stepped Wedge Cluster Randomized Trial

Conditions
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Septic Shock

Intervention / Treatment
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* Other: Minifluid challenge
* Other: Usual practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient (Age > 18 years) Admitted in ICU for less than 3 days. Abdominal (excepted urinary tract infection) or pulmonary related septic shock, defined by SEPSIS III criteria diagnosed within less than 12 hours. Written consent or oral by the patient (and/or consent signed by the next of skin) Patient has social security affiliation or who beneficiary of such social security Exclusion Criteria: Patient with life expectancy inferior to 24 hours at the time of inclusion. Cardiac arrest Allergy to albumin Pregnancy Traumatic brain injury Limitation of invasive therapeutics, palliative care Patient under guardianship or curatorship

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: stepped wedge cluster randomized trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Minifluid challenge<br>100 ml of 4% Albumin will be deliver to assess fluid responsiveness | Other: Minifluid challenge<br>* Pragmatic optimization fluid management protocol based on Mini-Fluid Challenge (MFC) in treating an acute circulatory failure. MFC consist of an infusion of 100 ml of colloid solution (4% human serum albumin) during 1 minute via a separate venous line. Before and after each MFC and depending on the hemodynamic device used, the attending physician will perform a first set of hemodynamic measurements, including cardiac index (CI) or cardiac output (CO); stroke volume (SV), indexed stroke volume (iSV) or velocity time index (VTI). If the variation in measurement is superior to 10%, the attending physician will infuse 400 ml of buffered crystalloid solution or saline solution. After an infusion of 500 ml, fluid responsiveness will be evaluated with CI or CO measurement. For non-responders, fluid challenge must be stopped and other therapeutics should be considered. For responder, another MFC should be consider if hemodynamic status is not stabilized.<br>|
| Experimental: Control<br>Patient will be treated as defined by most recent surviving sepsis campaign guidelines | Other: Usual practice<br>* Patients included in control group will be managed according to the last surviving sepsis recommendations edited in 2017.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Delta SOFA score (Day0 - Day5) | Delta SOFA score is the difference between SOFA (Sepsis-related Organ Failure Assessment) measured at day 0 and at Day 5. SOFA score was developed to quantify organ dysfunction in patients with sepsis and to determine treatment effectiveness. SOFA score is a scale range from 0 to 24, with higher scores indicating worse organ dysfunction. Five organs dysfunctions are analyzed: Respiratory: PaO2/FiO2 ratio Cardio-vascular: severity of hypotension and need of vasopressors (µ/kg/min) Renal: creatinine (mg/dl) Hemostasis: Platelet count (G/l) Liver: Bilirubin (mg/dl) Neurologic: Glasgow coma scale | Day 5 | 
| ICU length of stay until ability to ICU discharge |  | 90 days | 
| Length of stay in hospital |  | 90 days | 
| Ventilator free days at day 28 |  | 28 days | 
| Renal failure free days at day 28 |  | 28 days | 
| Catecholamine free days at day 10 |  | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at day 28 |  | 28 days | 
| Mortality at day 90 |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Fluid optimisation, Minifluid challenge, Fluid overload