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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.
GOAL study is a stepped wedge cluster-randomized trial. Centers will switch randomly from the control to the intervention at regular intervals:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Minifluid challenge | Experimental | 100 ml of 4% Albumin will be deliver to assess fluid responsiveness |
|
| Control | Experimental | Patient will be treated as defined by most recent surviving sepsis campaign guidelines |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minifluid challenge | Other | 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. |
| 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:
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality at day 28 | 28 days | |
| Mortality at day 90 | 90 days |
| Measure | Description | Time Frame |
|---|---|---|
| SF-36 (Short-Form 36) | The SF-36 is an indicator of health status and quality of life. The SF-36 has eight dimensions; the scores are weighted sums of the questions in each section. This scores range from 0 - 100. Lower scores indicate more disability and higher scores less disability. The eight dimensions of this score are:
|
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Angers university hospital | Angers | France | ||||
| Besançon university hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26903338 | Background | 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. | |
| 24638143 |
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All collected data that underlie results in a publication
All collected data that underlie results in a publication
Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
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stepped wedge cluster randomized trial
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|
| Usual practice | Other | Patients included in control group will be managed according to the last surviving sepsis recommendations edited in 2017. |
|
| 6 months |
| CANTAB test (Cambridge Neuropsychological Test Automated Battery) | CANTAB test have demonstrated sensitivity to detecting changes in neuropsychological performance and include tests of working memory, learning and executive function; visual, verbal and episodic memory; attention, information processing and reaction time; social and emotion recognition, decision making and response control | 6 months |
| PCL-5 | Quality of life with PCL-5 questionnaire | 6 months |
| Besançon |
| France |
| Brest university hospital | Brest | 29200 | France |
| Brest university hospital | Brest | France |
| Chartres Hospital | Chartres | 28000 | France |
| Clermont Ferrand university hospital | Clermont-Ferrand | France |
| Le Mans hospital | Le Mans | France |
| Marseille university horpital | Marseille | France |
| Morlaix hospital | Morlaix | France |
| Nantes university hospital | Nantes | France |
| Nîmes university hospital | Nîmes | 30029 | France |
| George Pompidou university hospital (APHP) | Paris | France |
| Kremlin Bicêtre university hospital (APHP) | Paris | France |
| Poitiers university hospital | Poitiers | France |
| Rouen university hospital | Rouen | France |
| Toulon hospital | Toulon | France |
| Tours university hospital | Tours | France |
| Hôpital privé de l'ouest parisen | Trappes | 78190 | France |
| Background |
| Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000-2012. JAMA. 2014 Apr 2;311(13):1308-16. doi: 10.1001/jama.2014.2637. |
| 11794169 | Background | Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001 Nov 8;345(19):1368-77. doi: 10.1056/NEJMoa010307. |
| 25432556 | Background | Malbrain ML, Marik PE, Witters I, Cordemans C, Kirkpatrick AW, Roberts DJ, Van Regenmortel N. Fluid overload, de-resuscitation, and outcomes in critically ill or injured patients: a systematic review with suggestions for clinical practice. Anaesthesiol Intensive Ther. 2014 Nov-Dec;46(5):361-80. doi: 10.5603/AIT.2014.0060. |
| 28101605 | Background | 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. |
| 27922878 | Background | Sakr Y, Rubatto Birri PN, Kotfis K, Nanchal R, Shah B, Kluge S, Schroeder ME, Marshall JC, Vincent JL; Intensive Care Over Nations Investigators. Higher Fluid Balance Increases the Risk of Death From Sepsis: Results From a Large International Audit. Crit Care Med. 2017 Mar;45(3):386-394. doi: 10.1097/CCM.0000000000002189. |
| 28130687 | Background | Marik PE, Linde-Zwirble WT, Bittner EA, Sahatjian J, Hansell D. Fluid administration in severe sepsis and septic shock, patterns and outcomes: an analysis of a large national database. Intensive Care Med. 2017 May;43(5):625-632. doi: 10.1007/s00134-016-4675-y. Epub 2017 Jan 27. |
| 26162676 | Background | 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. |
| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D004487 | Edema |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D012816 | Signs and Symptoms |
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