Clinical trial NCT04580888: Emergency Echocardiography in Sepsis
Official title: Impact of Early Haemodynamic Assessment by Echocardiography on Organ Dysfunction of Patients Admitted in the Emergency Department for Sepsis or Septic Shock
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Sepsis
Echocardiography
Organ Dysfunction Syndrome Sepsis
Emergencies
Keywords: Sepsis
Echocardiography
Haemodynamic
Emergency Medicine
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2020-10-09
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Sequential Organ Failure Assessment (SOFA) score
timeFrame: change from Hour 0 at Day 1
Secondary outcomes:
measure: Interruption of fluid resuscitation
timeFrame: Hour 3
measure: Maintains of fluid resuscitation
timeFrame: Hour 3
measure: Initiation of inotropes
timeFrame: Hour 3
measure: Initiation of vasopressor support
timeFrame: Hour 3
measure: Therapeutic modification
timeFrame: Hour 3
measure: Persisting hypovolemia
timeFrame: Hour 0
measure: Left ventricular failure
timeFrame: Hour 0
measure: Vasoplegia with left ventricular hyperkinesia
timeFrame: Hour 0
measure: Right ventricular failure
timeFrame: Hour 0
measure: Stabilized hemodynamic status
timeFrame: Hour 0
measure: Hydrostatic pulmonary edema
timeFrame: through study completion, an average of 1 month
measure: Supraventricular arrhythmias
timeFrame: through study completion, an average of 1 month
measure: ventricular arrhythmias
timeFrame: through study completion, an average of 1 month
measure: acute coronary syndrome,
timeFrame: through study completion, an average of 1 month
measure: ischemic stroke
timeFrame: through study completion, an average of 1 month
measure: hemorrhagic stroke
timeFrame: through study completion, an average of 1 month
measure: Lactate clearance
timeFrame: Hour 0 to Hour 6
measure: septic shock
timeFrame: Hour 24
measure: Patient course
timeFrame: through study completion, an average of 1 month
measure: Mortality
timeFrame: Day 7 and through study completion, an average of 1 month
Other outcomes:
Locations:
city: Albi
country: France
facility: CH d'Albi
city: Eaubonne
country: France
facility: CH d'Eaubonne - Montmorency
city: La Tronche
country: France
facility: Grenoble university hospital
city: Limoges
country: France
facility: Limgoes university hospital
city: Lyon
country: France
facility: Hospices civils de Lyon
city: Nantes
country: France
facility: Nantes university hospital
city: Nice
country: France
facility: Nice university hospital
city: Poitiers
country: France
facility: Poitiers university hospital
city: Saint-Pierre
country: France
facility: La réunion university hospital
city: Toulouse
country: France
facility: Toulouse university hospital
Study officials:
References: