Emergency Echocardiography in Sepsis

Sepsis Clinical Trial

— GENESIS  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04580888
• Other study ID #: 87RI19_0038 (GENESIS)
• Status: Recruiting
• Phase: N/A
• Start date: July 23, 2021
• Est. completion date: August 23, 2025

Study information

• Verified date: December 2023
• Source: University Hospital, Limoges
• Contact: LAFON Thomas, MD
• Phone: 555056254
• Email: thomas.lafon[@]chu-limoges.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 312
• Est. completion date: August 23, 2025
• Est. primary completion date: August 23, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Echocardiography
• Emergencies
• Organ Dysfunction Syndrome Sepsis
• Sepsis
• Systemic Inflammatory Response Syndrome
• Toxemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CH d'Albi	Albi
France	Bordeaux university hospital	Bordeaux
France	CH d'Eaubonne - Montmorency	Eaubonne
France	Grenoble university hospital	La Tronche
France	Hopital de Versailles	Le Chesnay
France	Limgoes university hospital	Limoges
France	Hospices civils de Lyon	Lyon
France	Nantes university hospital	Nantes
France	Nice university hospital	Nice
France	Hopital lariboisière	Paris
France	Poitiers university hospital	Poitiers
France	La réunion university hospital	Saint-Pierre
France	Toulouse university hospital	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Limoges

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Persisting hypovolemia	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Secondary	Left ventricular failure	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Secondary	Vasoplegia with left ventricular hyperkinesia	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Secondary	Right ventricular failure	Number and proportion of patients presenting at the time of early hemodynamic assessment using echocardiography (intervention arm)	Hour 0
Secondary	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
Secondary	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
Secondary	Supraventricular arrhythmias	Number of Supraventricular arrhythmias since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
Secondary	ventricular arrhythmias	Number of ventricular arrhythmias since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
Secondary	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
Secondary	ischemic stroke	Number of ischemic stroke since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
Secondary	hemorrhagic stroke	Number of hemorrhagic stroke since potentially related to the initiation of positive inotropes	through study completion, an average of 1 month
Secondary	Lactate clearance	Lactate clearance (lactate 6h after randomization compared to lactate at baseline)	Hour 0 to Hour 6
Secondary	septic shock	Number and proportion of patients who developed septic shock 24 h after inclusion	Hour 24
Secondary	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
Secondary	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