Hemodynamics InstabilityGENIUSNCT05336357
Non-invasive Goal-directed thErapy oN cIrcUlatory Shock
A study testing Goal-Directed Therapy in people with Hemodynamics Instability, run by University of Sao Paulo at 1 site in Brazil.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodynamics Instability
- What is being tested?
- Goal-Directed Therapy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 380 participants
- Where
- 1 siteBrazil
- Study dates
- 20 Feb 2024to 30 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
Show all 9Show fewer
- Capillary refill time > 3 s (after digital compression for 10 seconds);
- Poor skin perfusion.
- Signed Informed Consent Form.
Who cannot join
- 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
Show all 9Show fewer
- Patients with ST-segment elevation Myocardial Infarction
- Patients requiring Invasive Mechanical Ventilation
- Patients already participating in another study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Brazil1 site, 1 recruiting
- Recruiting
Instituto do Coração
São Paulo, 05403-000
Ludhmila Hajjar, MD, PhD, +55 11 2661-4246, ludhmila@usp.br
About this study
Official title: The Effect of Non-invasive Hemodynamic Goal-directed Therapy on the Incidence of Acute Kidney Injury in Circulatory Shock: a Randomized Clinical Trial
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..
Read the 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
- Being tested
- Goal-Directed Therapy
- Keywords
- Shock, Sepsis, Early Goal Directed Therapy
- Medical subject headings
- Shock, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Goal-Directed TherapyDevice
Also called ClearSight™ System
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.
| Study group | Role | What they receive |
|---|---|---|
| Goal-Directed Therapy Group | Experimental | 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. Receives: Device: Goal-Directed Therapy |
| Conventional Therapy Group | No intervention | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Resuscitation after 6 hours of treatment
Time to Resuscitation: After 6 hours of treatment, the number of patients who achieve the following goals:
Mean arterial pressure > 65mmHg Urine output greater than 0.5 mL/kg/h for more than 2 hours, and/or Decrease of more than 10% in serum lactate compared to the initial value
Measured: 6 hours
Secondary outcomes (8)
Number of Participants with Myocardial Injury
Presence of elevated troponin levels to values above the 99th percentile.
Measured: 30 days
Number of Participants with Acute Myocardial Infarction
Presence of Myocardial Injury, associated with at least one of the following factors:
- Symptoms of acute myocardial ischemia;
- Dynamic alteration on Electrocardiogram;
- Evidence of new myocardial segmental contractility loss, diagnosed by Echocardiogram and/or Cardiac Resonance.
Measured: 30 days
Patients with Acute Kidney Injury
Number of patients with Acute Kidney Injury within 72 hours
Measured: 72 hours
Assessment of health costs
The health costs will be measured in US dollars using the Brazilian Public Health database, which contains data on procedures, medicines, and hospital stay prices.
Measured: 1 year
Length of hospital stay
Length of the patient's hospital stay
Measured: 180 days
Amount of fluid administered
- Amount of fluid administered, fluid balance, and the amount of vasoactive and inotropic drugs administered
Measured: at the time of randomization, 2 hours, 6 hours, 24 hours, 48 hours, and 72 hours
Quality of life assessment
The assessment of quality of life will be made using the EQ-5D Dimensions questionnaire (EQ-5D), which consists of an instrument that assesses five dimensions (mobility, personal care, usual activities, pain/discomfort and anxiety/depression), where the patient indicates the degree of impairment in each dimension, in addition to a visual scale that varies from zero to one hundred, in relation to their perception of health on the day of the test, with one hundred indicating the best possible level of health, and zero indicating the worst possible level. This questionnaire was validated for use in the Brazilian population.
Measured: Hospital admission and at 30 days
Rate of mortality
Mortality at 30 days and 6 months
Measured: 30 days and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2022
- Study start20 Feb 2024
- Primary completion22 Feb 2026 (estimated)
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (23)Papers the sponsor has linked to this study.
- Other trials for Hemodynamics InstabilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 380 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto Dante Pazzanese de Cardiologia
- Responsible party
- Principal investigator, Ludhmila Abrahão Hajjar MD, PhD, University of Sao Paulo
- Investigators
- Ludhmila A Hajjar, MD, PhD, Principal investigator, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05336357
- Sponsor's protocol ID
- GENIUS
- Acronym
- GENIUS
- Status last verified
- Aug 2024
- First submitted
- 17 Mar 2022
- Last updated
- 26 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13.
PubMed 25392034Gonzalez-Hermosillo JA, Palma-Carbajal R, Rojas-Velasco G, Cabrera-Jardines R, Gonzalez-Galvan LM, Manzur-Sandoval D, Jimenez-Rodriguez GM, Ortiz-Solis WA. Hemodynamic profiles related to circulatory shock in cardiac care units. Arch Cardiol Mex. 2020;90(1):47-54. doi: 10.24875/ACM.19000016.
PubMed 31996854Sakr Y, Reinhart K, Vincent JL, Sprung CL, Moreno R, Ranieri VM, De Backer D, Payen D. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med. 2006 Mar;34(3):589-97. doi: 10.1097/01.CCM.0000201896.45809.E3.
PubMed 16505643Vincent JL. Understanding cardiac output. Crit Care. 2008;12(4):174. doi: 10.1186/cc6975. Epub 2008 Aug 22.
PubMed 18771592Kislitsina ON, Rich JD, Wilcox JE, Pham DT, Churyla A, Vorovich EB, Ghafourian K, Yancy CW. Shock - Classification and Pathophysiological Principles of Therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi: 10.2174/1573403X15666181212125024.
PubMed 30543176Swan HJ, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med. 1970 Aug 27;283(9):447-51. doi: 10.1056/NEJM197008272830902. No abstract available.
PubMed 5434111Auler JO Jr, Galas FR, Sundin MR, Hajjar LA. Auler JO Jr, Galas FR, Sundin MR, Hajjar LA: Arterial pulse pressure variation predicting fluid responsiveness in critically ill patients. Shock 30(Suppl 1):18-22, 2008. Shock. 2009 May;31(5):542. doi: 10.1097/SHK.0b013e3181a2e492. No abstract available.
PubMed 19365234Sangkum L, Liu GL, Yu L, Yan H, Kaye AD, Liu H. Minimally invasive or noninvasive cardiac output measurement: an update. J Anesth. 2016 Jun;30(3):461-80. doi: 10.1007/s00540-016-2154-9. Epub 2016 Mar 9.
PubMed 26961819De Backer D, Bakker J, Cecconi M, Hajjar L, Liu DW, Lobo S, Monnet X, Morelli A, Myatra SN, Perel A, Pinsky MR, Saugel B, Teboul JL, Vieillard-Baron A, Vincent JL. Alternatives to the Swan-Ganz catheter. Intensive Care Med. 2018 Jun;44(6):730-741. doi: 10.1007/s00134-018-5187-8. Epub 2018 May 3.
PubMed 29725695Teboul JL, Saugel B, Cecconi M, De Backer D, Hofer CK, Monnet X, Perel A, Pinsky MR, Reuter DA, Rhodes A, Squara P, Vincent JL, Scheeren TW. Less invasive hemodynamic monitoring in critically ill patients. Intensive Care Med. 2016 Sep;42(9):1350-9. doi: 10.1007/s00134-016-4375-7. Epub 2016 May 7.
PubMed 27155605Kobe J, Mishra N, Arya VK, Al-Moustadi W, Nates W, Kumar B. Cardiac output monitoring: Technology and choice. Ann Card Anaesth. 2019 Jan-Mar;22(1):6-17. doi: 10.4103/aca.ACA_41_18.
PubMed 30648673Broch O, Renner J, Gruenewald M, Meybohm P, Schottler J, Caliebe A, Steinfath M, Malbrain M, Bein B. A comparison of the Nexfin(R) and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery. Anaesthesia. 2012 Apr;67(4):377-83. doi: 10.1111/j.1365-2044.2011.07018.x. Epub 2012 Feb 11.
PubMed 22324797Bubenek-Turconi SI, Craciun M, Miclea I, Perel A. Noninvasive continuous cardiac output by the Nexfin before and after preload-modifying maneuvers: a comparison with intermittent thermodilution cardiac output. Anesth Analg. 2013 Aug;117(2):366-72. doi: 10.1213/ANE.0b013e31829562c3. Epub 2013 Jun 11.
PubMed 23757471Sokolski M, Rydlewska A, Krakowiak B, Biegus J, Zymlinski R, Banasiak W, Jankowska EA, Ponikowski P. Comparison of invasive and non-invasive measurements of haemodynamic parameters in patients with advanced heart failure. J Cardiovasc Med (Hagerstown). 2011 Nov;12(11):773-8. doi: 10.2459/JCM.0b013e32834cfebb.
PubMed 21941196Hamilton MA, Cecconi M, Rhodes A. A systematic review and meta-analysis on the use of preemptive hemodynamic intervention to improve postoperative outcomes in moderate and high-risk surgical patients. Anesth Analg. 2011 Jun;112(6):1392-402. doi: 10.1213/ANE.0b013e3181eeaae5. Epub 2010 Oct 21.
PubMed 20966436
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Non-invasive Hemodynamic Goal-directed Therapy on the Incidence of Acute Kidney Injury in Circulatory Shock: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05336357
- Acronym / sponsor ID
- GENIUS / GENIUS
- Conditions
- Hemodynamics Instability
- Keywords
- Shock, Sepsis, Early Goal Directed Therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 380 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Instituto Dante Pazzanese de Cardiologia
- Study start
- 20 Feb 2024 (actual)
- Primary completion
- 22 Feb 2026 (estimated)
- Study completion
- 30 Oct 2026 (estimated)
- First posted
- 20 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Goal-Directed Therapy Group | Experimental | Device: Goal-Directed TherapyPatients 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. |
| Conventional Therapy Group | No intervention | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- Signed Informed Consent Form.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Goal-Directed TherapyAlso: ClearSight™ SystemPatients 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. | Device | Goal-Directed Therapy Group |
Primary outcome
Time to Resuscitation after 6 hours of treatment
Time frame: 6 hours
Time to Resuscitation: After 6 hours of treatment, the number of patients who achieve the following goals: Mean arterial pressure > 65mmHg Urine output greater than 0.5 mL/kg/h for more than 2 hours, and/or Decrease of more than 10% in serum lactate compared to the initial value
8 secondary outcomes
Number of Participants with Myocardial Injury
Time frame: 30 days
Number of Participants with Acute Myocardial Infarction
Time frame: 30 days
Patients with Acute Kidney Injury
Time frame: 72 hours
Assessment of health costs
Time frame: 1 year
Length of hospital stay
Time frame: 180 days
Amount of fluid administered
Time frame: at the time of randomization, 2 hours, 6 hours, 24 hours, 48 hours, and 72 hours
Quality of life assessment
Time frame: Hospital admission and at 30 days
Rate of mortality
Time frame: 30 days and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2024.
- Background: PubMed 25392034Cecconi M, De Backer D, Antonelli M, Beale R, Bakker J, Hofer C, Jaeschke R, Mebazaa A, Pinsky MR, Teboul JL, Vincent JL, Rhodes A. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med. 2014 Dec;40(12):1795-815. doi: 10.1007/s00134-014-3525-z. Epub 2014 Nov 13.
- Background: PubMed 31996854Gonzalez-Hermosillo JA, Palma-Carbajal R, Rojas-Velasco G, Cabrera-Jardines R, Gonzalez-Galvan LM, Manzur-Sandoval D, Jimenez-Rodriguez GM, Ortiz-Solis WA. Hemodynamic profiles related to circulatory shock in cardiac care units. Arch Cardiol Mex. 2020;90(1):47-54. doi: 10.24875/ACM.19000016.
- Background: PubMed 16505643Sakr Y, Reinhart K, Vincent JL, Sprung CL, Moreno R, Ranieri VM, De Backer D, Payen D. Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study. Crit Care Med. 2006 Mar;34(3):589-97. doi: 10.1097/01.CCM.0000201896.45809.E3.
- Background: PubMed 18771592Vincent JL. Understanding cardiac output. Crit Care. 2008;12(4):174. doi: 10.1186/cc6975. Epub 2008 Aug 22.
- Background: PubMed 30543176Kislitsina ON, Rich JD, Wilcox JE, Pham DT, Churyla A, Vorovich EB, Ghafourian K, Yancy CW. Shock - Classification and Pathophysiological Principles of Therapeutics. Curr Cardiol Rev. 2019;15(2):102-113. doi: 10.2174/1573403X15666181212125024.
- Background: PubMed 5434111Swan HJ, Ganz W, Forrester J, Marcus H, Diamond G, Chonette D. Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. N Engl J Med. 1970 Aug 27;283(9):447-51. doi: 10.1056/NEJM197008272830902. No abstract available.
- Background: PubMed 19365234Auler JO Jr, Galas FR, Sundin MR, Hajjar LA. Auler JO Jr, Galas FR, Sundin MR, Hajjar LA: Arterial pulse pressure variation predicting fluid responsiveness in critically ill patients. Shock 30(Suppl 1):18-22, 2008. Shock. 2009 May;31(5):542. doi: 10.1097/SHK.0b013e3181a2e492. No abstract available.
- Background: PubMed 26961819Sangkum L, Liu GL, Yu L, Yan H, Kaye AD, Liu H. Minimally invasive or noninvasive cardiac output measurement: an update. J Anesth. 2016 Jun;30(3):461-80. doi: 10.1007/s00540-016-2154-9. Epub 2016 Mar 9.
- Background: PubMed 29725695De Backer D, Bakker J, Cecconi M, Hajjar L, Liu DW, Lobo S, Monnet X, Morelli A, Myatra SN, Perel A, Pinsky MR, Saugel B, Teboul JL, Vieillard-Baron A, Vincent JL. Alternatives to the Swan-Ganz catheter. Intensive Care Med. 2018 Jun;44(6):730-741. doi: 10.1007/s00134-018-5187-8. Epub 2018 May 3.
- Background: PubMed 27155605Teboul JL, Saugel B, Cecconi M, De Backer D, Hofer CK, Monnet X, Perel A, Pinsky MR, Reuter DA, Rhodes A, Squara P, Vincent JL, Scheeren TW. Less invasive hemodynamic monitoring in critically ill patients. Intensive Care Med. 2016 Sep;42(9):1350-9. doi: 10.1007/s00134-016-4375-7. Epub 2016 May 7.
- Background: PubMed 30648673Kobe J, Mishra N, Arya VK, Al-Moustadi W, Nates W, Kumar B. Cardiac output monitoring: Technology and choice. Ann Card Anaesth. 2019 Jan-Mar;22(1):6-17. doi: 10.4103/aca.ACA_41_18.
- Background: PubMed 22324797Broch O, Renner J, Gruenewald M, Meybohm P, Schottler J, Caliebe A, Steinfath M, Malbrain M, Bein B. A comparison of the Nexfin(R) and transcardiopulmonary thermodilution to estimate cardiac output during coronary artery surgery. Anaesthesia. 2012 Apr;67(4):377-83. doi: 10.1111/j.1365-2044.2011.07018.x. Epub 2012 Feb 11.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ludhmila A Hajjar, MD, PhD principal investigator
University of Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Goal-Directed Therapy in people with Hemodynamics Instability, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ludhmila A Hajjar, MD, PhD (+55 11 26615795, ludhmila@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to Resuscitation after 6 hours of treatment (time frame: 6 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05336357, which also lists 23 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2024.