Emergency Echocardiography in Sepsis (GENESIS)

Impact of Early Haemodynamic Assessment by Echocardiography on Organ Dysfunction of Patients Admitted in the Emergency Department for Sepsis or Septic Shock

Acute circulatory failure that combines hypovolemia, vasoplegia and cardiac dysfunction plays a major role in the development of sepsis-related organ dysfunction. Pathophysiological mechanisms are multiple and complex. The objective of the GENESIS study is to determine the impact of early haemodynamic assessment using echocardiography in association with a therapeutic algorithm (intervention arm), when compared with standard of care based on the current Surviving Sepsis Campaign (SSC) recommendations (control arm), on the development of organ dysfunctions in patients admitted to the Emergency Department for sepsis or septic shock.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Emergencies; Echocardiography; Organ Dysfunction Syndrome Sepsis
• Intervention / Treatment: Procedure: early transthoracic echocardiography; Procedure: standards of care

Detailed Description

Sepsis is currently defined as life-threatening organ dysfunction secondary to a dysregulated host response to infection (Sepsis-3). Septic shock is a subgroup of patients who also have sustained arterial hypotension requiring vasopressors and tissue dysoxia. The mortality varies from 10 to 40% depending on the severity. The latest "bundles" of the SSC request to perform within the first hour of sepsis identification a fluid loading of 30 mL/kg of crystalloids in the presence of hypotension, and to initiate a vasopressor support in case of persistent hypotension to maintain a mean arterial pressure ≥ 65 mmHg. However, early fluid resuscitation is not necessarily associated with an improvement of sepsis prognosis and may even be deleterious when leading to excessive positive fluid balance. Accordingly, the SSC recommends investigating a personalized approach to define for each patient the appropriate volume of fluids to be administered according to the initial mechanism of sepsis-induced cardiovascular failure. Echocardiography is currently recommended as a first-line modality to identify the origin of acute circulatory failure, sepsis remaining the leading cause. It has been shown to alter ongoing treatment based on the sole SSC recommendations in the intensive care unit. In contrast, the impact of hemodynamic assessment using echocardiography at the early stage of sepsis in patients admitted to the Emergency Department (ED) is unknown.

In this randomized trial, patients will be either assessed hemodynamically using transthoracic echocardiography to guide early therapeutic management (intervention arm) or managed according to standards of care based on current SSC recommendations (control arm). Early echocardiography will be performed after 500 mL of fluid loading initiated upon identification of septic patients based on the qSOFA score (hemodynamic criterion required: systolic blood pressure ≤ 100 mmHg). This will allow identifying the hemodynamic profile at the origin of sepsis-induced circulatory failure and to monitor both the efficacy and tolerance of fluid resuscitation, or of any other therapeutic intervention (e.g., inotropic support) according to a predefined therapeutic algorithm. Patients allocated to the control arm will be managed conventionally according to current SSC recommendations, including a standardized fluid loading of 30 mL/kg.

Organ dysfunctions will be assessed in the two study arms by the SOFA score 24 hours after randomization and patient will be followed up until hospital discharge to determine outcome.

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: LAFON Thomas, MD; Phone Number: +33 555056254; Email: thomas.lafon@chu-limoges.fr
• Study Contact Backup: Name: BOURZEIX Paul, MD; Phone Number: +33 555058841; Email: paul.bourzeix@chu-limoges.fr

Study Locations

• France
  • Albi, France, 81000
    • Recruiting
    • CH d'Albi
    • Contact: Arthur BAISSE, MD; Email: arthurbaisse@hotmail.com
    • Principal Investigator: Arthur BAISSE, MD
  • Bordeaux, France, 33076
    • Withdrawn
    • Bordeaux university hospital
  • Eaubonne, France, 95600
    • Recruiting
    • CH d'Eaubonne - Montmorency
    • Contact: Maxime GAUTIER, MD; Phone Number: +33 134066755; Email: maxime.gautier@ch-simoneveil.fr
    • Principal Investigator: Maxime GAUTIER, MD
  • La Tronche, France, 38700
    • Recruiting
    • Grenoble University Hospital
    • Contact: Damien VIGLINO, MD; Phone Number: +33 476765934; Email: dviglino@chu-grenoble.fr
    • Principal Investigator: DAMIEN VIGLINO, MD
  • Le Chesnay, France, 78150
    • Recruiting
    • Hopital de Versailles
    • Contact: Ludovic DALLE, MD; Email: ldalle@ch-versailles.fr
    • Principal Investigator: Ludovic DALLE, MD
  • Limoges, France, 87042
    • Recruiting
    • Limgoes university hospital
    • Contact: LAFON Thomas, MD; Phone Number: +33 555056254; Email: thomas.lafon@chu-limoges.fr
    • Contact: BOURZEIX Paul, MD; Phone Number: +33 555058841; Email: paul.bourzeix@chu-limoges.fr
    • Principal Investigator: LAFON Thomas, MD
    • Sub-Investigator: BAISSE Arthur, MD
  • Lyon, France, 69003
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Cécile DELAHAYE, MD; Phone Number: +33 472119572; Email: cecile.delahaye@chu-lyon.fr
    • Principal Investigator: Cécile DELAHAYE, MD
  • Nantes, France, 44093
    • Recruiting
    • Nantes university hospital
    • Contact: Philippe LE CONTE, MD; Phone Number: +33 240083934; Email: philippe.leconte@chu-nantes.fr
    • Principal Investigator: Philippe LE CONTE, MD
  • Nice, France, 06600
    • Recruiting
    • Nice University Hospital
    • Contact: Julie CONTENTI, MD; Phone Number: +33 492033242; Email: contenti.j@chu-nice.fr
  • Paris, France, 75010
    • Recruiting
    • Hôpital Lariboisière
    • Contact: Anthony CHAUVIN, MD; Email: anthony.chauvin@aphp.fr
    • Principal Investigator: Anthony CHAUVIN, MD
  • Poitiers, France, 86000
    • Recruiting
    • Poitiers university hospital
    • Principal Investigator: Nicolas MARJANOVIC, MD
    • Contact: Nicolas MARJANOVIC, MD; Phone Number: +33 549444444; Email: nicolas.marjanovic@chu-poitiers.fr
  • Saint-Pierre, France, 97410
    • Recruiting
    • La réunion university hospital
    • Contact: Adrien VAGUE, MD; Phone Number: +33 693130226; Email: adrien.vague@chu-reunion.fr
    • Principal Investigator: Adrien VAGUE, MD
  • Toulouse, France, 31059
    • Recruiting
    • Toulouse University Hospital
    • Contact: Frédéric BALEN, MD; Phone Number: +33 561772379; Email: balen.f@chu-toulouse.fr
    • Principal Investigator: Frédéric BALEN, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients admitted to the ED
• Age ≥ 18 years and affiliation to Social Security
• With sepsis (Sepsis-3 definition):

Clinically suspected or documented acute infection

AND a quick score Sequential Organ Failure Assessment (qSOFA) ≥ 2 points with:

• Systolic blood pressure ≤ 100 mmHg (1 point) requiring fluid loading
• AND encephalopathy (1 point) OR respiratory rate ≥ 22 cpm (1 point) AND a systolic blood pressure ≤ 100 mmHg after 500 mL of crystalloid vascular filling - Informed consent

Exclusion Criteria:

• Decision to limit care or moribund status
• Pregnancy or breast feeding
• Subject under juridical protection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Assessment using an early transthoracic echocardiography (after 500 mL of fluids) to identify the hemodynamic profile responsible for the acute circulatory failure associated with sepsis / septic shock and to guide ongoing treatment (therapeutic algorithm) and monitor its efficacy and tolerance.	Procedure: early transthoracic echocardiography; In the intervention arm, echocardiography will be performed immediately and potentially repeated to confirm the need for additional fluid resuscitation up to 30 mL/kg in the presence of persisting hypovolemia, or not (e.g., severe ventricular dysfunction). A therapeutic algorithm will allow standardized impact on ongoing management according to the hemodynamic profile identified by early echocardiography. After the completion of initial fluid resuscitation up to 30 mL/kg if required, a new echocardiographic assessment will be systematically performed by the same operator to stop or not fluid resuscitation, and to potentially initiate another treatment according to both the hemodynamic profile and clinical context.
Other: Control arm; Conventional management according to current standards of care based on SSC recommendations, including a standardized fluid resuscitation of 30 mL/kg.	Procedure: standards of care; In the control arm, patients will be treated according to standards of care based on current SSC recommendations, including a fluid resuscitation of 30 mL/kg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sequential Organ Failure Assessment (SOFA) score	Crude variation of the SOFA score between inclusion and 24h following randomization.	change from Hour 0 at Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interruption of fluid resuscitation	Number and proportion of patients in whom echocardiography performed in the ED (intervention arm) modified ongoing therapy based on SSC recommendations (standard of care) according to the hemodynamic profile. Interruption of fluid resuscitation before having administrated 30 mL/kg	Hour 3
Maintains of fluid resuscitation	Number and proportion of patients in whom echocardiography performed in the ED (intervention arm) modified ongoing therapy based on SSC recommendations (standard of care) according to the hemodynamic profile. Fluid resuscitation maintained beyond 30 mL/kg	Hour 3
Initiation of inotropes	Number and proportion of patients in whom echocardiography performed in the ED (intervention arm) modified ongoing therapy based on SSC recommendations (standard of care) according to the hemodynamic profile. Initiation of inotropes	Hour 3
Initiation of vasopressor support	Number and proportion of patients in whom echocardiography performed in the ED (intervention arm) modified ongoing therapy based on SSC recommendations (standard of care) according to the hemodynamic profile. Initiation of vasopressor support	Hour 3
Therapeutic modification	Number and proportion of patients in whom echocardiography performed in the ED (intervention arm) modified ongoing therapy based on SSC recommendations (standard of care) according to the hemodynamic profile. Therapeutic modification directly related to the echocardiographic examination	Hour 3
Persisting hypovolemia	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Left ventricular failure	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Vasoplegia with left ventricular hyperkinesia	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Right ventricular failure	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Stabilized hemodynamic status	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm). Stabilized hemodynamic status (none of above-mentioned abnormalities) due to adequate management of acute circulatory failure (avoid any deleterious therapeutic change).	Hour 0
Hydrostatic pulmonary edema	Number of Hydrostatic pulmonary edema (cardiogenic or volume overload) since potentially related to excessive fluid loading	through study completion, an average of 1 month
Supraventricular arrhythmias	Number of Supraventricular arrhythmias since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
ventricular arrhythmias	Number of ventricular arrhythmias since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
acute coronary syndrome,	Number of acute coronary syndrome since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
ischemic stroke	Number of ischemic stroke since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
hemorrhagic stroke	Number of hemorrhagic stroke since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
Lactate clearance	Lactate clearance (lactate 6h after randomization compared to lactate at baseline)	Hour 0 to Hour 6
septic shock	Number and proportion of patients who developed septic shock 24 h after inclusion	Hour 24
Patient course	Patient course after emergency department discharge: hospitalization in regular ward (medicine / surgery), stepdown unit or intensive care unit.	through study completion, an average of 1 month
Mortality	Mortality (all-cause and sepsis-related) at Day 7 and at hospital discharge	Day 7 and through study completion, an average of 1 month

Collaborators and Investigators

• Sponsor: University Hospital, Limoges

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2021
• Primary Completion (Estimated): August 23, 2025
• Study Completion (Estimated): August 23, 2025

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 9, 2020

Study Record Updates

• Last Update Posted (Estimated): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Emergency Medicine; Sepsis; Echocardiography; Haemodynamic
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Disease Attributes; Shock; Sepsis; Toxemia; Emergencies; Systemic Inflammatory Response Syndrome
• Other Study ID Numbers: 87RI19_0038 (GENESIS)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No