NCT05336357

Non-invasive Goal-directed thErapy oN cIrcUlatory Shock

The Effect of Non-invasive Hemodynamic Goal-directed Therapy on the Incidence of Acute Kidney Injury in Circulatory Shock: a Randomized Clinical Trial

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 380 (estimated)
• Sponsor: University of Sao Paulo · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

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

• Hemodynamics Instability

Interventions

Type	Name	Description
DEVICE	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.

Timeline

• Start date: 2024-02-20
• Primary completion: 2026-02-22
• Completion: 2026-10-30
• First posted: 2022-04-20
• Last updated: 2024-08-26

Locations

1 site across 1 country: Brazil