Non-invasive Goal-directed thErapy oN cIrcUlatory Shock

NCT05336357 | Recruiting DMC

• 1 other identifier: GENIUS
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief 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..

Conditions

Hemodynamics Instability

Keywords

Shock; Sepsis; Early Goal Directed Therapy

Outcome Measures

Primary Outcomes (1)

• 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

  6 hours

Secondary Outcomes (8)

• Number of Participants with Myocardial Injury

  30 days

• Number of Participants with Acute Myocardial Infarction

  30 days

• Patients with Acute Kidney Injury

  72 hours

• Assessment of health costs

  1 year

• Length of hospital stay

  180 days

Study Arms (2)

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.

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.

Interventions

Goal-Directed Therapy 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.

Also known as: ClearSight™ System

Goal-Directed Therapy Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo: lead
• Instituto Dante Pazzanese de Cardiologia: collaborator

Study Sites (1)

Instituto do Coração

São Paulo, 05403-000, Brazil

RECRUITING

Related Publications (23)

• 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.

  PMID: 25392034 BACKGROUND

• Gonzalez-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.

  PMID: 31996854 BACKGROUND

• Sakr 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.

  PMID: 16505643 BACKGROUND

• Vincent JL. Understanding cardiac output. Crit Care. 2008;12(4):174. doi: 10.1186/cc6975. Epub 2008 Aug 22.

  PMID: 18771592 BACKGROUND

• Kislitsina 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.

  PMID: 30543176 BACKGROUND

• Swan 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.

  PMID: 5434111 BACKGROUND

• Auler 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.

  PMID: 19365234 BACKGROUND

• Sangkum 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.

  PMID: 26961819 BACKGROUND

• De 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.

  PMID: 29725695 BACKGROUND

• Teboul 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.

  PMID: 27155605 BACKGROUND

• Kobe 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.

  PMID: 30648673 BACKGROUND

• Broch 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.

  PMID: 22324797 BACKGROUND

• Bubenek-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.

  PMID: 23757471 BACKGROUND

• Sokolski 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.

  PMID: 21941196 BACKGROUND

• Hamilton 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.

  PMID: 20966436 BACKGROUND

• Geisen M, Rhodes A, Cecconi M. Less-invasive approaches to perioperative haemodynamic optimization. Curr Opin Crit Care. 2012 Aug;18(4):377-84. doi: 10.1097/MCC.0b013e328355894f.

  PMID: 22732438 BACKGROUND

• Giglio M, Manca F, Dalfino L, Brienza N. Perioperative hemodynamic goal-directed therapy and mortality: a systematic review and meta-analysis with meta-regression. Minerva Anestesiol. 2016 Nov;82(11):1199-1213. Epub 2016 Apr 13.

  PMID: 27075210 BACKGROUND

• Pearse RM, Harrison DA, MacDonald N, Gillies MA, Blunt M, Ackland G, Grocott MP, Ahern A, Griggs K, Scott R, Hinds C, Rowan K; OPTIMISE Study Group. Effect of a perioperative, cardiac output-guided hemodynamic therapy algorithm on outcomes following major gastrointestinal surgery: a randomized clinical trial and systematic review. JAMA. 2014 Jun 4;311(21):2181-90. doi: 10.1001/jama.2014.5305.

  PMID: 24842135 BACKGROUND

• Kapoor PM, Kakani M, Chowdhury U, Choudhury M, Lakshmy, Kiran U. Early goal-directed therapy in moderate to high-risk cardiac surgery patients. Ann Card Anaesth. 2008 Jan-Jun;11(1):27-34. doi: 10.4103/0971-9784.38446.

  PMID: 18182756 BACKGROUND

• Osawa EA, Rhodes A, Landoni G, Galas FR, Fukushima JT, Park CH, Almeida JP, Nakamura RE, Strabelli TM, Pileggi B, Leme AC, Fominskiy E, Sakr Y, Lima M, Franco RA, Chan RP, Piccioni MA, Mendes P, Menezes SR, Bruno T, Gaiotto FA, Lisboa LA, Dallan LA, Hueb AC, Pomerantzeff PM, Kalil Filho R, Jatene FB, Auler Junior JO, Hajjar LA. Effect of Perioperative Goal-Directed Hemodynamic Resuscitation Therapy on Outcomes Following Cardiac Surgery: A Randomized Clinical Trial and Systematic Review. Crit Care Med. 2016 Apr;44(4):724-33. doi: 10.1097/CCM.0000000000001479.

  PMID: 26646462 BACKGROUND

• Aya HD, Cecconi M, Hamilton M, Rhodes A. Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis. Br J Anaesth. 2013 Apr;110(4):510-7. doi: 10.1093/bja/aet020. Epub 2013 Feb 27.

  PMID: 23447502 BACKGROUND

• Nowak RM, Nanayakkara P, DiSomma S, Levy P, Schrijver E, Huyghe R, Autunno A, Sherwin RL, Divine G, Moyer M. Noninvasive hemodynamic monitoring in emergency patients with suspected heart failure, sepsis and stroke: the PREMIUM registry. West J Emerg Med. 2014 Nov;15(7):786-94. doi: 10.5811/westjem.2014.8.21357. Epub 2014 Sep 23.

  PMID: 25493119 BACKGROUND

• McGregor D, Sharma S, Gupta S, Ahmad S, Godec T, Harris T. Emergency department non-invasive cardiac output study (EDNICO): a feasibility and repeatability study. Scand J Trauma Resusc Emerg Med. 2019 Mar 11;27(1):30. doi: 10.1186/s13049-019-0586-6.

  PMID: 30867006 BACKGROUND

MeSH Terms

Conditions

Shock; Sepsis

Interventions

Early Goal-Directed Therapy

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Critical Care; Patient Care; Therapeutics

Study Officials

• Ludhmila A Hajjar, MD, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ludhmila A Hajjar, MD, PhD

CONTACT

+55 11 26615795; ludhmila@usp.br

ARO F InCor, MD

CONTACT

+55 11 26615795; aro@incor.usp.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 17, 2022
• First Posted: April 20, 2022
• Study Start: February 20, 2024
• Primary Completion: February 22, 2026
• Study Completion (Estimated): October 30, 2026
• Last Updated: August 26, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)