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

NCT03461900 | Completed

• 1 other identifier: 29BRC18.0054
• Study Type: interventional
• Target: 535
• Locations: 1 country
• Sites: 18

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.

Conditions

Septic Shock

Keywords

Septic shock; Fluid optimisation; Minifluid challenge; Fluid overload

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• Mortality at day 28

  28 days

• Mortality at day 90

  90 days

Other Outcomes (3)

• SF-36 (Short-Form 36)

  6 months

• CANTAB test (Cambridge Neuropsychological Test Automated Battery)

  6 months

• PCL-5

  6 months

Study Arms (2)

Minifluid challenge

EXPERIMENTAL

100 ml of 4% Albumin will be deliver to assess fluid responsiveness

Other: Minifluid challenge

Control

EXPERIMENTAL

Patient will be treated as defined by most recent surviving sepsis campaign guidelines

Other: Usual practice

Interventions

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.

Minifluid challenge

Usual practice OTHER

Patients included in control group will be managed according to the last surviving sepsis recommendations edited in 2017.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Cardiac arrest
• Allergy to albumin
• Pregnancy
• Traumatic brain injury
• Limitation of invasive therapeutics, palliative care
• Patient under guardianship or curatorship

Sponsors & Collaborators

• University Hospital, Brest: lead

Study Sites (18)

Angers university hospital

Angers, France

Location

Besançon university hospital

Besançon, France

Location

Brest university hospital

Brest, 29200, France

Location

Brest university hospital

Brest, France

Location

Chartres Hospital

Chartres, 28000, France

Location

Clermont Ferrand university hospital

Clermont-Ferrand, France

Location

Le Mans hospital

Le Mans, France

Location

Marseille university horpital

Marseille, France

Location

Morlaix hospital

Morlaix, France

Location

Nantes university hospital

Nantes, France

Location

Nîmes university hospital

Nîmes, 30029, France

Location

George Pompidou university hospital (APHP)

Paris, France

Location

Kremlin Bicêtre university hospital (APHP)

Paris, France

Location

Poitiers university hospital

Poitiers, France

Location

Rouen university hospital

Rouen, France

Location

Toulon hospital

Toulon, France

Location

Tours university hospital

Tours, France

Location

Hôpital privé de l'ouest parisen

Trappes, 78190, France

Location

Related Publications (8)

• 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.

  PMID: 26903338 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.

  PMID: 24638143 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.

  PMID: 11794169 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.

  PMID: 25432556 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.

  PMID: 28101605 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.

  PMID: 27922878 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.

  PMID: 28130687 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.

  PMID: 26162676 BACKGROUND

MeSH Terms

Conditions

Shock, Septic; Edema

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: stepped wedge cluster randomized trial

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 12, 2018
• Study Start: June 4, 2019
• Primary Completion: August 9, 2023
• Study Completion: January 8, 2024
• Last Updated: September 19, 2025

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: All collected data that underlie results in a publication
• Access Criteria: 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.

Locations

FR (18)