Clinical trial NCT03461900: Guided Fluid-balance Optimization With Mini-fluid chALlenge During Septic Shock
Official title: Guided Fluid-balance Optimization With Mini-fluid chALlenge During Septic Shock: A Multicenter, Stepped Wedge Cluster Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Septic Shock
Keywords: Septic shock
Fluid optimisation
Minifluid challenge
Fluid overload
Lead sponsor: University Hospital, Brest
Sponsor class: OTHER
First posted: 2018-03-12
Enrollment: 535
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: stepped wedge cluster randomized trial
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Delta SOFA score (Day0 - Day5)
timeFrame: Day 5
measure: ICU length of stay until ability to ICU discharge
timeFrame: 90 days
measure: Length of stay in hospital
timeFrame: 90 days
measure: Ventilator free days at day 28
timeFrame: 28 days
measure: Renal failure free days at day 28
timeFrame: 28 days
measure: Catecholamine free days at day 10
timeFrame: 10 days
Secondary outcomes:
measure: Mortality at day 28
timeFrame: 28 days
measure: Mortality at day 90
timeFrame: 90 days
Other outcomes:
measure: SF-36 (Short-Form 36)
timeFrame: 6 months
measure: CANTAB test (Cambridge Neuropsychological Test Automated Battery)
timeFrame: 6 months
measure: PCL-5
timeFrame: 6 months
Locations:
city: Angers
country: France
facility: Angers university hospital
city: Besançon
country: France
facility: Besançon university hospital
city: Brest
country: France
facility: Brest university hospital
city: Brest
country: France
facility: Brest university hospital
city: Chartres
country: France
facility: Chartres Hospital
city: Clermont-Ferrand
country: France
facility: Clermont Ferrand university hospital
city: Le Mans
country: France
facility: Le Mans hospital
city: Marseille
country: France
facility: Marseille university horpital
city: Morlaix
country: France
facility: Morlaix hospital
city: Nantes
country: France
facility: Nantes university hospital
city: Nîmes
country: France
facility: Nîmes university hospital
city: Paris
country: France
facility: George Pompidou university hospital (APHP)
city: Paris
country: France
facility: Kremlin Bicêtre university hospital (APHP)
city: Poitiers
country: France
facility: Poitiers university hospital
city: Rouen
country: France
facility: Rouen university hospital
city: Toulon
country: France
facility: Toulon hospital
city: Tours
country: France
facility: Tours university hospital
city: Trappes
country: France
facility: Hôpital privé de l'ouest parisen
Study officials:
References:
citation: Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
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citation: Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Mar;43(3):304-377. doi: 10.1007/s00134-017-4683-6. Epub 2017 Jan 18.
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citation: Cecconi M, Hofer C, Teboul JL, Pettila V, Wilkman E, Molnar Z, Della Rocca G, Aldecoa C, Artigas A, Jog S, Sander M, Spies C, Lefrant JY, De Backer D; FENICE Investigators; ESICM Trial Group. Fluid challenges in intensive care: the FENICE study: A global inception cohort study. Intensive Care Med. 2015 Sep;41(9):1529-37. doi: 10.1007/s00134-015-3850-x. Epub 2015 Jul 11.