Non-invasive Goal-directed thErapy oN cIrcUlatory Shock

NCT ID: NCT05336357

Last Updated: 2024-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

380 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-02-20

Study Completion Date

2026-10-30

Brief Summary

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Circulatory shock occurs when the oxygen supply to the tissues decreases, leading to cellular damage and affecting about one-third of patients admitted to Intensive Care Units (ICUs). Cardiac Output (CO) is defined as the volume of blood ejected by the left ventricle per minute and is a crucial hemodynamic parameter for monitoring patients with signs of circulatory shock. However, this parameter is underutilized in patients treated in Emergency Units because its measurement typically involves invasive methods, which are not commonly available in this setting. Any method capable of measuring CO without the need for pulmonary artery catheter insertion is referred to as minimally invasive CO monitoring. Evaluating these parameters allows for a quicker determination of the etiology of circulatory shock, enabling the early initiation of goal-directed therapy. Goal-directed therapy has been proven effective in reducing morbidity and mortality, ICU length of stay, and mechanical ventilation duration in ICU patients who respond to fluid resuscitation. Currently, there are no data on the impact of a hemodynamic optimization strategy in patients during the early hours of shock.

The objective is to assess whether goal-directed hemodynamic therapy, through non-invasive hemodynamic monitoring, reduces the time required for hemodynamic resuscitation in patients with septic shock. A multicenter, randomized, open-label study will be conducted in Emergency Units, Intensive Care Units, and Hospital Wards.

Patients over 18 years old admitted with signs of septic shock (defined as systolic blood pressure less than 90 mmHg and/or mean arterial pressure less than 65 mmHg, along with at least one of the following criteria: lactate greater than 2 mEq/L, oliguria, neurological alteration, or capillary refill time greater than 3 seconds) will be included Participants will be randomized in a 1:1 ratio into two groups. In the Goal-Directed Therapy Group, patients will be monitored using the HemoSphere HPI™ (Edwards Life Sciences, Irvine, CA, USA), where parameters such as cardiac index (CI), stroke volume (SV), systolic blood pressure (SBP), mean arterial pressure (MAP), and HPI will guide medical management. In the Conventional Therapy Group, patients will be evaluated with the standard hemodynamic monitoring equipment typically found in emergency units..

Detailed Description

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Introduction: Sepsis is a severe condition where the body responds inadequately to an infection. Septic shock is a subset of sepsis characterized by significantly increased mortality due to severe circulatory and/or cellular metabolism abnormalities. Septic shock involves persistent hypotension (defined as the need for vasopressors to maintain a mean arterial pressure ≥ 65 mm Hg and a serum lactate level \< 18 mg/dL \[2 mmol/L\]) despite adequate fluid resuscitation. Cardiac Output (CO) is defined as the volume of blood ejected by the left ventricle per minute and is a crucial hemodynamic parameter for monitoring patients with signs of circulatory shock, as it can aid in defining the etiology and management of such patients. However, this parameter is underutilized in patients treated in Emergency Units because its measurement typically involves invasive methods, which are not readily available in this setting. The pulmonary artery catheter is considered the gold standard for determining CO, but since it is an invasive method, other devices capable of providing this hemodynamic variable in a less invasive manner have been developed in recent decades. Any method capable of providing CO without the need for pulmonary artery catheter insertion is referred to as minimally invasive CO monitoring.

The potential advantages of using these methods include the simplicity of measurements, faster acquisition of hemodynamic parameters, and the possibility of implementing monitoring strategies in places such as emergency departments and urgent care settings. Evaluating these parameters allows for a quicker determination of the etiology of circulatory shock, enabling the early initiation of goal-directed therapy. It is known that the use of goal-directed therapy has proven effective in reducing morbidity and mortality in the peri- and postoperative periods of high-risk surgical patients; this strategy is also associated with reduced mortality, ICU length of stay, and mechanical ventilation duration in fluid-responsive ICU patients. To date, there are no data regarding the impact of hemodynamic optimization strategies in patients with septic shock during the early hours of shock.

Objective: To evaluate whether goal-directed hemodynamic therapy, through non-invasive hemodynamic monitoring, reduces the time required for hemodynamic resuscitation in patients with septic shock.

Methods: A multicenter, randomized, open-label study will be conducted in Emergency Units, Intensive Care Units, and Hospital Wards. The study will include patients over 18 years of age who are admitted to the emergency department with signs of septic shock (systolic blood pressure less than 90 mmHg and/or mean arterial pressure less than 65 mmHg, and at least one of the following: lactate greater than 2 mEq/L, oliguria, neurological alteration, or capillary refill time greater than 3 seconds) and who have signed the Informed Consent Form (ICF). Included patients will be randomized in a 1:1 ratio into two groups.

The Goal-Directed Therapy Group will consist of patients monitored by the HemoSphere HPI™ (Edwards Life Sciences, Irvine, CA, USA) in the first 6 hours after randomization, where the parameters cardiac index (CI), stroke volume (SV), systolic blood pressure (SBP), mean arterial pressure (MAP), and HPI will guide medical management. All patients in this group will receive the first dose of antibiotics within the first hour of diagnosing septic shock, as well as an infusion of 500 mL of crystalloid solution. After this infusion, those who continue to have an SV of less than 35 mL/beat and a CI of less than 2.2 L/min/m² will receive additional aliquots of crystalloid solution until the SV no longer increases by 10% relative to the initial value. If, after the first fluid infusion, the patient presents with an SV greater than or equal to 35 mL/beat and MAP less than 65 mmHg, a vasoactive drug will be started. If, after achieving hemodynamic stability, the patient has an HPI value greater than 85%, additional aliquots of crystalloid solution and/or adjustments in the vasoactive drug dose will be administered. For patients with an SV greater than 35 mL/beat and a CI less than 2.2 L/min/m², the initiation of an inotropic drug will be considered.

In the Conventional Therapy Group, patients will be evaluated using the usual hemodynamic monitoring equipment found in emergency units, including SBP, MAP, oxygen saturation, heart rate, and respiratory rate, as well as physical examination data. All patients will receive the first dose of antibiotics within the first hour of diagnosing septic shock. Patients will receive fluid resuscitation with crystalloid solution at a minimum of 30 mL/kg in the first 3 hours of treatment. If, after this resuscitation, the patient continues to have SBP less than 90 mmHg and/or MAP less than 65 mmHg, a vasoactive drug will be started. However, if at the diagnosis of septic shock the patient presents with SBP \< 90 mmHg, MAP \< 65 mmHg, or a drop in BP \> 40 mmHg, a vasoactive drug, such as norepinephrine, will be promptly started before fluid resuscitation.

Conditions

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Hemodynamics Instability

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Goal-Directed Therapy Group

Patients allocated to the Goal-Directed Therapy group will be monitored by the ClearSight™ System (Edwards Life Sciences, Irvine, CA, USA) in the first 24 hours after randomization, where the parameters Cardiac Index (CI), Stroke Volume (SV), Systolic Blood Pressure (SBP) and Mean Arterial Pressure (MAP) will be acquired continuously.

Group Type EXPERIMENTAL

Goal-Directed Therapy

Intervention Type DEVICE

Patients will be monitored by the ClearSight™ System (Edwards Life Sciences, Irvine, CA, USA) in the first 24 hours, where the parameters Cardiac Index (CI), Stroke Volume (SV), Systolic Blood Pressure (SBP) and Mean Arterial Pressure (MAP) will be acquired continuously. The treatment goal will be to keep the CI greater than or equal to 2.2 L/min/m2, the SV greater than or equal to 35 mL/beat, and the SBP greater than or equal to 90 mmHg and/or the MAP greater than or equal to 65 mmHg.

If the CI is below 2.2 L/min/m2 and the SV less than 35 mL/beat, an aliquot of 500 mL of crystalloid solution will be administered; if there is not an increase by 10% in the CI and SV values, a new aliquot of 250 mL may be administered; if this 10% increase does not occur for at least 20 minutes, inotropic medications will be started, with doses titrated periodically. If the pre-established goal is not reached, it is suggested to consider transfusion of a concentrated red blood cell.

Conventional Therapy Group

Patients allocated to the Conventional Therapy Group will be treated according to the assistant team of the Emergency Unit, where will be measured the following parameters: invasive or non-invasive blood pressure (decided by the assistant team), peripheral oximetry, heart and respiratory rate, urinary output, in association with clinical history, complete physical examination and laboratory and imaging tests.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Goal-Directed Therapy

Patients will be monitored by the ClearSight™ System (Edwards Life Sciences, Irvine, CA, USA) in the first 24 hours, where the parameters Cardiac Index (CI), Stroke Volume (SV), Systolic Blood Pressure (SBP) and Mean Arterial Pressure (MAP) will be acquired continuously. The treatment goal will be to keep the CI greater than or equal to 2.2 L/min/m2, the SV greater than or equal to 35 mL/beat, and the SBP greater than or equal to 90 mmHg and/or the MAP greater than or equal to 65 mmHg.

If the CI is below 2.2 L/min/m2 and the SV less than 35 mL/beat, an aliquot of 500 mL of crystalloid solution will be administered; if there is not an increase by 10% in the CI and SV values, a new aliquot of 250 mL may be administered; if this 10% increase does not occur for at least 20 minutes, inotropic medications will be started, with doses titrated periodically. If the pre-established goal is not reached, it is suggested to consider transfusion of a concentrated red blood cell.

Intervention Type DEVICE

Other Intervention Names

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ClearSight™ System

Eligibility Criteria

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Inclusion Criteria

* Age \> 18 years;
* Patients admitted to Emergency Units, Intensive Care Units, and Wards within 3 hours of the diagnosis of Septic Shock:
* Systolic Blood Pressure (SBP) \< 90 mmHg and/or Mean Arterial Pressure (MAP) \< 65 mmHg (with or without norepinephrine at a dose less than 0.5 mcg/kg/min) + Clinical signs of infection and at least one of the following:

* Lactate \> 2 mEq/L;
* Oliguria (urine output \< 0.5 mL/kg/h for at least 6 hours);
* Neurological changes (mental confusion, decreased level of consciousness, psychomotor agitation, temporal-spatial disorientation);
* Capillary refill time \> 3 s (after digital compression for 10 seconds);
* Poor skin perfusion.
* Signed Informed Consent Form.

Exclusion Criteria

* Hospital admission time greater than 24 hours
* Significant edema in the fingers
* Severe peripheral vasoconstriction
* Use of Norepinephrine at a dose greater than or equal to 0.5 mcg/kg/min
* Presence of significant Aortic Insufficiency
* Patients undergoing Renal Replacement Therapy
* Patients with ST-segment elevation Myocardial Infarction
* Patients requiring Invasive Mechanical Ventilation
* Patients already participating in another study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto Dante Pazzanese de Cardiologia

OTHER

Sponsor Role collaborator

University of Sao Paulo

OTHER

Sponsor Role lead

Responsible Party

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Ludhmila Abrahão Hajjar MD, PhD

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ludhmila A Hajjar, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Sao Paulo

Locations

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Instituto do Coração

São Paulo, , Brazil

Site Status RECRUITING

Countries

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Brazil

Central Contacts

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Ludhmila A Hajjar, MD, PhD

Role: CONTACT

+55 11 26615795

ARO F InCor, MD

Role: CONTACT

+55 11 26615795

Facility Contacts

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Ludhmila Hajjar, MD, PhD

Role: primary

+55 11 2661-4246

References

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Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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GENIUS

Identifier Type: -

Identifier Source: org_study_id

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