Fluid Intolerance Signals as Safety Limits to Prevent Fluid-induced Harm During Septic Shock Resuscitation

NCT06568744 | Recruiting

• 2 other identifiers: 2206070151230475
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this multicentric randomized controlled trial is to compare, in septic shock patients who require further fluid resuscitation, two strategies of administering fluids. The intervention group will integrate fluid intolerance signals to the decision making process, while the control group will follow standard of care, for a 6 hour study protocol. The main question it aims to answer is

1. 1.To compare the effect of both resuscitation strategies on fluid-induced harm, assessed by the change in pulmonary, cardiac, and renal function biomarkers during the study period.
2. 2.To assess the safety of both resuscitation strategies on hypoperfusion resolution, measured by the improvement of capillary refill time (CRT) and lactate during the study period.
3. 3.To determine the dynamics of the different fluid intolerance signals

Conditions

Septic Shock

Keywords

fluid overload; resuscitation; capillary refill time; POCUS

Outcome Measures

Primary Outcomes (1)

• Delta of PaO2: fraction of inspired oxygen (FiO2) ratio between 0-6 hours

  evolution of lung function during the study period (6h)

  6 hours

Secondary Outcomes (5)

• Delta of proBNP between 0-6 hours

  6 hours

• Delta of plasma neutrophil gelatinase-associated lipocalin (NGAL) between 0-6 hours

  6 hours

• Delta of creatinine between 0-6 hours

  6 hours

• Delta of capillary refill time between 0-6 hours

  6 hours

• Delta of arterial lactate between 0-6 hours

  6 hours

Other Outcomes (10)

• Delta of PaO2:FiO2 ratio between 24 hours

  24 hours

• Delta of plasma NGAL between 0-24 hours

  24 hours

• Delta of creatinine between 0-24 hours

  24 hours

Study Arms (2)

Intervention

EXPERIMENTAL

This group will follow a resuscitation algorithm aimed at macrohemodynamic stabilization and improvement of tissue hypoperfusion. Fluid administration will be tailored according to fluid responsiveness status, fluid intolerance signals, and hypoperfusion signals such as capillary refill time. Mechanical ventilation and sedation will follow standard management as per current recommendations.

Other: Intervention resuscitation

Standard of Care

ACTIVE COMPARATOR

This group will follow a resuscitation algorithm aimed at macrohemodynamic stabilization and improvement of tissue hypoperfusion. Fluid administration will be tailored according to fluid responsiveness status, and hypoperfusion signals such as capillary refill time. Mechanical ventilation and sedation will follow standard management as per current recommendations.

Other: Standard of Care resuscitation

Interventions

Intervention resuscitation OTHER

In fluid responsive patients, fluid intolerance will be checked. Lung Ultrasound (LUS): Anterior LUS with 4-point assessment at each hemithorax. Min:0 and a max:24. Low risk: \< 10; intermediate risk: 10-14 or delta of 2 points. High risk: \>14, or an increase \>4 from baseline. VExUS: Low risk: Grade 0-1. Intermediate risk: 2. High risk: 3 E/e' ratio: Low risk: \<8. Intermediate risk: 8-13. High risk \>14. Central venous pressure (CVP): Low risk \<12 mmHg. Intermediate risk: 12-15 mmHg or a delta of 3 mmHg. High risk \> 15 mmHg or \>5 mmHg increase after a fluid challenge. In low-risk, a fluid challenge of 500 ml of balanced crystalloid will be performed in 30 minutes. If intermediate risk, a fluid challenge of 250 ml of balanced crystalloid in 30 minutes. If high-risk signals, alternative strategies (vasopressor and inodilator tests) will be deployed. After each challenge, peripheral perfusion, fluid responsiveness and intolerance will be re-assessed.

Intervention

Standard of Care resuscitation OTHER

In fluid responsive patients, fluid challenges of 500 ml of balanced crystalloid will be performed in 30 minutes. After a fluid challenge, peripheral perfusion status and fluid responsiveness will be re-measured. If the patient persists with hypoperfusion, successive fluid challenges will be performed until hypoperfusion resolves or the patient becomes fluid unresponsive. If hypoperfusion signals persists and the patient becomes fluid unresponsive, alternative resuscitation interventions will be deployed, which include: 1) vasopressor titration to higher mean arterial pressure (MAP) targets in a MAP-test, and 2) addition of an inotrope to increase cardiac output in an inodilator test. If hypoperfusion fails to resolve, rescue therapies such as high-volume hemofiltration will be initiated.

Standard of Care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed or suspected septic shock
• \< 24 hours since diagnosis
• Hypoperfusion signal (altered arterial lactate or CRT) that requires further resuscitation
• Mechanical ventilation
• Positive fluid responsiveness status

You may not qualify if:

• Pregnancy
• Do-not-resuscitate status
• Acute coronary syndrome
• Active bleeding
• Severe concomitant acute respiratory distress syndrome (ARDS) (PaO2:FiO2 ratio \< 100)
• Anticipated surgery, prone positioning, or renal replacement therapy in the next 6 hours
• Refractory shock according to attending physician
• BMI \> 40.
• Inadequate echocardiographic window

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile: lead

Study Sites (3)

Hospital Biprovincial Quillota-Petorca

Quillota, Chile

RECRUITING

Hospital Barros Luco

Santiago, Chile

RECRUITING

Hospital Clinico UC Christus

Santiago, Chile

RECRUITING

Related Publications (7)

• Munoz F, Born P, Bruna M, Ulloa R, Gonzalez C, Philp V, Mondaca R, Blanco JP, Valenzuela ED, Retamal J, Miralles F, Wendel-Garcia PD, Ospina-Tascon GA, Castro R, Rola P, Bakker J, Hernandez G, Kattan E. Coexistence of a fluid responsive state and venous congestion signals in critically ill patients: a multicenter observational proof-of-concept study. Crit Care. 2024 Feb 19;28(1):52. doi: 10.1186/s13054-024-04834-1.

  PMID: 38374167 BACKGROUND

• Kenny JS, Prager R, Rola P, Haycock K, Basmaji J, Hernandez G. Unifying Fluid Responsiveness and Tolerance With Physiology: A Dynamic Interpretation of the Diamond-Forrester Classification. Crit Care Explor. 2023 Dec 12;5(12):e1022. doi: 10.1097/CCE.0000000000001022. eCollection 2023 Dec.

  PMID: 38094087 BACKGROUND

• Kattan E, Castro R, Miralles-Aguiar F, Hernandez G, Rola P. The emerging concept of fluid tolerance: A position paper. J Crit Care. 2022 Oct;71:154070. doi: 10.1016/j.jcrc.2022.154070. Epub 2022 Jun 2.

  PMID: 35660844 BACKGROUND

• Kattan E, Ospina-Tascon GA, Teboul JL, Castro R, Cecconi M, Ferri G, Bakker J, Hernandez G; ANDROMEDA-SHOCK Investigators. Systematic assessment of fluid responsiveness during early septic shock resuscitation: secondary analysis of the ANDROMEDA-SHOCK trial. Crit Care. 2020 Jan 23;24(1):23. doi: 10.1186/s13054-020-2732-y.

  PMID: 31973735 BACKGROUND

• Zampieri FG, Damiani LP, Bakker J, Ospina-Tascon GA, Castro R, Cavalcanti AB, Hernandez G. Effects of a Resuscitation Strategy Targeting Peripheral Perfusion Status versus Serum Lactate Levels among Patients with Septic Shock. A Bayesian Reanalysis of the ANDROMEDA-SHOCK Trial. Am J Respir Crit Care Med. 2020 Feb 15;201(4):423-429. doi: 10.1164/rccm.201905-0968OC.

  PMID: 31574228 BACKGROUND

• Hernandez G, Ospina-Tascon GA, Damiani LP, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Granda-Luna V, Cavalcanti AB, Bakker J; The ANDROMEDA SHOCK Investigators and the Latin America Intensive Care Network (LIVEN); Hernandez G, Ospina-Tascon G, Petri Damiani L, Estenssoro E, Dubin A, Hurtado J, Friedman G, Castro R, Alegria L, Teboul JL, Cecconi M, Cecconi M, Ferri G, Jibaja M, Pairumani R, Fernandez P, Barahona D, Cavalcanti AB, Bakker J, Hernandez G, Alegria L, Ferri G, Rodriguez N, Holger P, Soto N, Pozo M, Bakker J, Cook D, Vincent JL, Rhodes A, Kavanagh BP, Dellinger P, Rietdijk W, Carpio D, Pavez N, Henriquez E, Bravo S, Valenzuela ED, Vera M, Dreyse J, Oviedo V, Cid MA, Larroulet M, Petruska E, Sarabia C, Gallardo D, Sanchez JE, Gonzalez H, Arancibia JM, Munoz A, Ramirez G, Aravena F, Aquevedo A, Zambrano F, Bozinovic M, Valle F, Ramirez M, Rossel V, Munoz P, Ceballos C, Esveile C, Carmona C, Candia E, Mendoza D, Sanchez A, Ponce D, Ponce D, Lastra J, Nahuelpan B, Fasce F, Luengo C, Medel N, Cortes C, Campassi L, Rubatto P, Horna N, Furche M, Pendino JC, Bettini L, Lovesio C, Gonzalez MC, Rodruguez J, Canales H, Caminos F, Galletti C, Minoldo E, Aramburu MJ, Olmos D, Nin N, Tenzi J, Quiroga C, Lacuesta P, Gaudin A, Pais R, Silvestre A, Olivera G, Rieppi G, Berrutti D, Ochoa M, Cobos P, Vintimilla F, Ramirez V, Tobar M, Garcia F, Picoita F, Remache N, Granda V, Paredes F, Barzallo E, Garces P, Guerrero F, Salazar S, Torres G, Tana C, Calahorrano J, Solis F, Torres P, Herrera L, Ornes A, Perez V, Delgado G, Lopez A, Espinosa E, Moreira J, Salcedo B, Villacres I, Suing J, Lopez M, Gomez L, Toctaquiza G, Cadena Zapata M, Orazabal MA, Pardo Espejo R, Jimenez J, Calderon A, Paredes G, Barberan JL, Moya T, Atehortua H, Sabogal R, Ortiz G, Lara A, Sanchez F, Hernan Portilla A, Davila H, Mora JA, Calderon LE, Alvarez I, Escobar E, Bejarano A, Bustamante LA, Aldana JL. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA. 2019 Feb 19;321(7):654-664. doi: 10.1001/jama.2019.0071.

  PMID: 30772908 BACKGROUND

• Bagshaw SM, Brophy PD, Cruz D, Ronco C. Fluid balance as a biomarker: impact of fluid overload on outcome in critically ill patients with acute kidney injury. Crit Care. 2008;12(4):169. doi: 10.1186/cc6948. Epub 2008 Jul 24.

  PMID: 18671831 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 Officials

• Eduardo Kattan, MD, PhD

  Pontifiia Universidad Catolica de Chile

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eduardo Kattan, MD, PhD

CONTACT

+56223543292; e.kattan@gmail.com

Ricardo Castro, MD

CONTACT

+56223543292; rcastro.med@gmail.com

Study Design

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

Study Record Dates

• First Submitted: August 21, 2024
• First Posted: August 23, 2024
• Study Start: August 22, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: October 2, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: After study completion
• Access Criteria: upon reasonable request to the PI.

Locations

CL (3)