SepsisNCT07863323
Non-invasive Hemodynamic Optimization of Sepsis in Internal Medicine: a Randomized Study Comparing Therapy Guided by Non-invasive Hemodynamic Indices Versus Standard of Care.
A study testing non-invasive hemodynamic assessment and Treatment per SSC Guidelines in people with Sepsis and Septic Shock, run by Regione del Veneto - AULSS n. 7 Pedemontana at 2 sites in Italy.
Trial summary
Background and Rationale Sepsis affects 20 to 30 million people globally each year, with an estimated 48.9 million cases in 2017. Despite medical advances, it still carries a high risk of death. Since sepsis progresses rapidly, early treatment is essential. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Septic Shock
- What is being tested?
- non-invasive hemodynamic assessment and Treatment per SSC Guidelines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 430 participants
- Where
- 2 sitesItaly
- Study dates
- 3 Jun 2025to Nov 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
- Provision of specific informed consent;
- Confirmed or suspected diagnosis of sepsis, defined according to the latest SSC guidelines as: "the presence of a clear or suspected infection with life-threatening organ dysfunction caused by a dysregulated host response to infection indicated by a SOFA (Sequential Organ Failure Assessment) score ≥ 2";
- Patients of both sexes, aged 18 years or older;
- Patients evaluated in the Emergency Department for suspected infection requiring hospital admission, at the General Medicine ward of Ospedale Alto Vicentino in Santorso (VI, Italy) or the Emergency Medicine ward of the Policlinico Universitario of Pisa (Italy).
Who cannot join
- Stay in the Emergency Department of more than six hours, considered as the time between ED admission and ward admission;
- Administration of more than 1000 cc of crystalloid therapy in the three hours prior to patient arrival in the ward;
- Any admission from a facility or ward other than the Emergency Department;
- Sepsis related to an ongoing hospital stay or any sepsis not fitting the definition of community-acquired infection;
- Previous hospital admission within four weeks prior to ED access;
- Sepsis related to trauma;
Show all 12Show fewer
- Presence of severe oncological disease with life expectancy less than 3 months at enrollment;
- Active major bleeding;
- Dialysis therapy;
- Suspected or confirmed pregnancy;
- Age under 18 years;
- Patients who do not provide informed consent to the study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Italy2 sites, 2 recruiting
- Recruiting
Policlinico Universitario di Pisa - UOC Medicina d'Urgenza
Pisa, Pisa, 56124
Lorenzo Ghiadoni, Prof., +39 050-996120, medurguni@ao-pisa.toscana.it
- Recruiting
AULSS 7 Pedemontana - UOC Medicina Generale PO Alto Vicentino - Santorso (VI)
Santorso, Vicenza, 36014
Massimo Marchetti, Dr., +39 0445 571608, massimo.marchetti@aulss7.veneto.it
About this study
Official title: Ottimizzazione Emodinamica Non-invasiva Della Sepsi in Medicina Interna: Studio Randomizzato di Confronto Tra Terapia Diretta Agli Indici Emodinamici Non-invasivi Versus Standard di Cura. Codice Protocollo: EMODINAMICA_SEPSI
Background and Rationale Sepsis affects 20 to 30 million people globally each year, with an estimated 48.9 million cases in 2017. Despite medical advances, it still carries a high risk of death. Since sepsis progresses rapidly, early treatment is essential. This includes not only starting antibiotics quickly but also managing fluid levels effectively. Research suggests that in sepsis, fluid problems are often due to poor distribution in the body rather than an actual lack of fluids.
Currently, fluid and blood pressure management is often based only on monitoring arterial pressure, which may not provide a full picture of what's happening in the patient's circulatory system. More advanced indicators like Stroke Volume, Cardiac Output, and Peripheral Vascular Resistance can offer better guidance to optimize treatment and improve outcomes.
Read more
New non-invasive devices such as NICaS (Non-Invasive Cardiac System) make it easier and faster to monitor these values. NICaS uses electrical impedance technology and is approved by both the FDA and CE. It is easy to use, does not require specialized training, and allows for a more personalized and accurate treatment approach by tracking key heart and circulation parameters in real time.
Primary Objective
The main goal of this study is to compare two treatment strategies for patients with sepsis admitted to medical wards, and see which one leads to better survival:
- Fluid and/or vasopressor therapy guided by non-invasive hemodynamic monitoring (using NICaS), based on values like Stroke Volume, Cardiac Power Index, and Peripheral Vascular Resistance.
- Standard fluid therapy based on the international Surviving Sepsis Campaign (SSC) guidelines.
Secondary Objectives
- Use of vasopressors: Check which strategy leads to less frequent use of vasopressor drugs and shorter treatment duration with them.
- Kidney function: See which method is linked to fewer cases needing dialysis or kidney support.
- Timing of vasopressors: Understand if giving vasopressors earlier leads to better short- and mid-term outcomes, such as lower death rates after 30 days, fewer ICU admissions, and shorter hospital stays.
- Albumin levels and circulation: Track how blood albumin levels change with circulation status, to see if there's a link with fluid leakage (capillary leak) and risk of death.
- Fluid balance: Analyze how fluid gains and losses relate to changes in heart and circulation measurements.
- Microcirculation: Test if adding signs of small vessel (microcirculation) issues to the main heart and blood flow indicators improves predictions of how patients will do.
- Prediction scores: Investigate whether combining NICaS readings with common scoring systems like SOFA or APACHE helps doctors predict patient outcomes more accurately.
- Time to stability: Compare how quickly patients in each treatment group recover to a stable condition. According to Rosenthal and Kavic's criteria, a patient is considered stable when: -Their illness is improving -There's low risk of getting worse again - Organ support is stable - There's little chance of new problems arising - There are no major complications.
Conclusion This study aims to evaluate whether a more personalized approach using real-time, non-invasive hemodynamic monitoring can lead to better outcomes in septic patients compared to standard care. If successful, this method could help reduce deaths, complications, and treatment costs in sepsis management.
Read the detailed description
This study is a prospective, multicenter, randomized, open-label, parallel-group interventional trial designed to compare two different strategies for the hemodynamic management of patients with sepsis admitted to medical wards. Participants will be randomly assigned in a 1:1 ratio to either a usual-care strategy or a treatment strategy guided by serial non-invasive hemodynamic monitoring.
The hemodynamic-guided strategy uses the Non-Invasive Cardiac System (NICaS; NI Medical, Petah-Tikva, Israel), an impedance-based non-invasive hemodynamic monitoring device. NICaS provides measurements of several macrohemodynamic parameters, including cardiac index, stroke volume index, cardiac power index, systemic vascular resistance index, and total body water. These measurements are used to characterize the patient's hemodynamic profile and to assess changes following fluid administration and during subsequent treatment.
After enrollment, patients assigned to the hemodynamic-guided group undergo an initial non-invasive hemodynamic assessment followed by a standardized fluid challenge consisting of 10 mL/kg of crystalloid administered over 20 minutes. A subsequent NICaS assessment is performed to evaluate the hemodynamic response to fluid administration, including changes in stroke volume and other hemodynamic parameters. The resulting hemodynamic profile is used to support decisions regarding continuation of fluid therapy and/or initiation or adjustment of vasopressor therapy.
During the first 12 hours after enrollment, serial non-invasive hemodynamic assessments are performed at 180-minute intervals. Based on the evolution of the measured parameters and the patient's clinical condition, fluid and/or vasopressor therapy may be modified with the aim of optimizing the patient's hemodynamic status. Treatment modifications, fluid administration, vasopressor therapy, and relevant clinical parameters are recorded prospectively.
Patients randomized to the usual-care group are managed according to current clinical practice and applicable Surviving Sepsis Campaign recommendations. Fluid resuscitation and subsequent decisions regarding fluid administration and vasopressor therapy are made by the treating physician according to the patient's clinical condition and response to treatment.
In both groups, standardized clinical and laboratory reassessments are performed at predefined time points during the initial days after enrollment. These assessments include vital signs, fluid intake, urine output, blood gas analysis, laboratory parameters, and clinical assessment of organ function. Clinical severity scores are also recorded according to the study protocol. In the hemodynamic-guided group, the serial non-invasive hemodynamic measurements provide additional information to support treatment decisions.
The study will compare the clinical course of patients managed using usual care with that of patients managed using additional serial non-invasive hemodynamic information. In addition to the primary clinical outcome, the study will examine treatment requirements, organ support, fluid balance, vasopressor use, changes in organ dysfunction, and relationships between hemodynamic parameters and other clinical characteristics.
Participants will be followed during hospitalization and for 30 days after enrollment. Vital status and other relevant clinical information will be collected during follow-up.
- Conditions
- Sepsis, Septic Shock
- Being tested
- non-invasive hemodynamic assessment, Treatment per SSC Guidelines
- Keywords
- sepsis, septic shock, non invasive hemodynamics, fluid therapy, vasopressors
- Medical subject headings
- Sepsis, Shock, Septic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-invasive hemodynamic assessmentDiagnostic test
Patients will be evaluated with non-invasive hemodynamic monitoring using NICaS, measuring cardiac index, stroke volume, cardiac power, vascular resistance, and total body water. A fluid challenge (10 ml/kg crystalloids in 20 minutes) will assess fluid responsiveness. Patients with >15% stroke volume increase ("fluid responders") will continue hydration therapy per guidelines. Those with ≤15% increase or altered hemodynamics ("fluid non-responders") will start vasopressor treatment. Hemodynamic monitoring repeats every 3 hours for 12 hours to guide therapy adjustments aiming to optimize key parameters (CI, SV, CPI, SVRI). All treatments, fluid balances, and vital signs are recorded systematically.
Treatment per SSC GuidelinesOther
Patients receive fluid resuscitation with 30 ml/kg crystalloids over 3 hours. Fluid responsiveness is assessed by blood pressure increase and urine output.
Fluid responders (MAP >65 mmHg and urine output >1 ml/kg/h) continue maintenance fluids (1-2 ml/kg/h), adjusted by the physician.
Non-fluid responders (MAP ≤65 mmHg or urine output <1 ml/kg/h) start vasopressors to maintain MAP >65 mmHg, with dosage and fluid therapy managed by the physician.
All therapy changes are recorded.
| Study group | Role | What they receive |
|---|---|---|
| A - Usual Care strategy | Active comparator | Treatment per SSC Guidelines
Patients receive fluid resuscitation with 30 ml/kg crystalloids over 3 hours. Fluid responsiveness is assessed by blood pressure increase and urine output.
Fluid responders (MAP >65 mmHg and urine output >1 ml/kg/h) continue maintenance fluids (1-2 ml/kg/h), adjusted by the physician.
Non-fluid responders (MAP ≤65 mmHg or urine output <1 ml/kg/h) start vasopressors to maintain MAP >65 mmHg, with dosage and fluid therapy managed by the physician.
All therapy changes are recorded. Receives: Other: Treatment per SSC Guidelines |
| B - Strategy guided by non-invasive hemodynamic assessment | Experimental | For patients enrolled in arm B, a non-invasive hemodynamic assessment will be performed using the Non-Invasive Cardiac System (NICaS, NI Medical, Israel). The following parameters will be recorded: cardiac index (CI), stroke volume index (SV), cardiac power index (CPI), systemic vascular resistance index (SVRI), and total body water percentage (TBW).
A fluid challenge will then be administered with 10 ml/kg of crystalloids over 20 minutes to assess fluid responsiveness. Hemodynamic response post-fluid challenge will be measured via NICaS. A SV increase >15% defines a "fluid responder" who will continue fluid therapy at 1-2 ml/kg/hr per guidelines. Those with less than 15% SV increase, decreased SVRI, or altered CPI are "fluid non-responders" and will receive vasopressor support, adjusted and recorded accordingly.
Hemodynamic evaluations via NICaS will be repeated every 180 minutes for the first 12 hours. Therapy will be adjusted to optimize CI, SV, CPI, SVRI. Receives: Diagnostic Test: non-invasive hemodynamic assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality at 30 days
The primary endpoint of the study will be all-cause mortality at 30 days from hospital admission. Patient survival will be determined using one of the following methods: review of medical records, phone calls to the patient or their designated contact, or to the healthcare facility.
Measured: 30 days from hospital admission
Secondary outcomes (8)
Need for organ support
Proportion of participants who require initiation of mechanical ventilation and/or renal replacement therapy after study enrollment during the hospitalization period.
Measured: From enrollment through hospital discharge
Days free of organ support
defined as a patient alive and without assisted breathing, new invasive renal replacement therapy, or use of vasopressors (excluding vasopressor use before 48 hours). Each day a patient is alive and free of organ support counts as a day alive and free of organ support.
Measured: 30 days after enrollment
Hours free of renal replacement therapy
the number of hours between enrollment and the start of renal replacement therapy. If a decision is made to initiate palliative care instead of renal replacement therapy, the hours counted will be from enrollment until the decision to start palliative care.
Measured: 30 days after enrollment
Initiation of vasopressor therapy
Proportion of participants requiring initiation of vasopressor therapy after study enrollment. The use of vasopressors will be recorded during the hospitalization period, including the type of vasopressor and the time of initiation.
Measured: From enrollment through hospital discharge
Hours free of vasopressor
the number of hours between patient admission and start of vasopressor therapy. Patients requiring vasopressors who are instead started on palliative support therapy will be assigned "hours free of vasopressor" until the decision to start palliative care.
Measured: 30 days after enrollment
Change in SOFA score from baseline
Change in the Sequential Organ Failure Assessment (SOFA) score from the score recorded at study enrollment to subsequent daily assessments during hospitalization. The SOFA score will be calculated at enrollment and daily during the hospitalization period.
Measured: From enrollment through hospital discharge, assessed daily
Early mortality
mortality at 48 hours and 7 days
Measured: 48 hours and 7 days
Length of stay
Number of days from study enrollment to hospital discharge. For participants who die before hospital discharge, the length of stay will be calculated from enrollment to the date of in-hospital death.
Measured: From enrollment through hospital discharge or in-hospital death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2026
- Study start3 Jun 2025
- Primary completionOct 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies 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
- 430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Regione del Veneto - AULSS n. 7 Pedemontana
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital of Pisa
- Responsible party
- Principal investigator, Massimo Marchetti, Regione del Veneto - AULSS n. 7 Pedemontana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07863323
- Sponsor's protocol ID
- 592CET
- Status last verified
- Sep 2026
- First submitted
- 30 May 2025
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bauer M, Gerlach H, Vogelmann T, Preissing F, Stiefel J, Adam D. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Crit Care. 2020 May 19;24(1):239. doi: 10.1186/s13054-020-02950-2.
PubMed 32430052Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014 Jan 1;5(1):4-11. doi: 10.4161/viru.27372. Epub 2013 Dec 11.
PubMed 24335434Kingren MS, Starr ME, Saito H. Divergent Sepsis Pathophysiology in Older Adults. Antioxid Redox Signal. 2021 Dec;35(16):1358-1375. doi: 10.1089/ars.2021.0056. Epub 2021 Oct 1.
PubMed 34210173Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.
PubMed 31954465Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, Allegranzi B, Reinhart K. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020 Aug;46(8):1552-1562. doi: 10.1007/s00134-020-06151-x. Epub 2020 Jun 22.
PubMed 32572531Fleischmann-Struzek C, Rudd K. Challenges of assessing the burden of sepsis. Med Klin Intensivmed Notfmed. 2023 Dec;118(Suppl 2):68-74. doi: 10.1007/s00063-023-01088-7. Epub 2023 Nov 17.
PubMed 37975898Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
PubMed 26903338Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
PubMed 34599691
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ottimizzazione Emodinamica Non-invasiva Della Sepsi in Medicina Interna: Studio Randomizzato di Confronto Tra Terapia Diretta Agli Indici Emodinamici Non-invasivi Versus Standard di Cura. Codice Protocollo: EMODINAMICA_SEPSI
- ClinicalTrials.gov ID
- NCT07863323
- Acronym / sponsor ID
- 592CET
- Conditions
- Sepsis, Septic Shock
- Keywords
- sepsis, septic shock, non invasive hemodynamics, fluid therapy, vasopressors
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 430 participants (estimated)
- Lead sponsor
- Regione del Veneto - AULSS n. 7 PedemontanaUniversity, hospital or other
- Collaborators
- University Hospital of Pisa
- Study start
- 3 Jun 2025 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 7 Oct 2026 (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.
Background and Rationale Sepsis affects 20 to 30 million people globally each year, with an estimated 48.9 million cases in 2017. Despite medical advances, it still carries a high risk of death. Since sepsis progresses rapidly, early treatment is essential. This includes not only starting antibiotics quickly but also managing fluid levels effectively. Research suggests that in sepsis, fluid problems are often due to poor distribution in the body rather than an actual lack of fluids.
Currently, fluid and blood pressure management is often based only on monitoring arterial pressure, which may not provide a full picture of what's happening in the patient's circulatory system. More advanced indicators like Stroke Volume, Cardiac Output, and Peripheral Vascular Resistance can offer better guidance to optimize treatment and improve outcomes.
New non-invasive devices such as NICaS (Non-Invasive Cardiac System) make it easier and faster to monitor these values. NICaS uses electrical impedance technology and is approved by both the FDA and CE. It is easy to use, does not require specialized training, and allows for a more personalized and accurate treatment approach by tracking key heart and circulation parameters in real time.
Primary Objective
The main goal of this study is to compare two treatment strategies for patients with sepsis admitted to medical wards, and see which one leads to better survival:
- Fluid and/or vasopressor therapy guided by non-invasive hemodynamic monitoring (using NICaS), based on values like Stroke Volume, Cardiac Power Index, and Peripheral Vascular Resistance.
- Standard fluid therapy based on the international Surviving Sepsis Campaign (SSC) guidelines.
Secondary Objectives
- Use of vasopressors: Check which strategy leads to less frequent use of vasopressor drugs and shorter treatment duration with them.
- Kidney function: See which method is linked to fewer cases needing dialysis or kidney support.
- Timing of vasopressors: Understand if giving vasopressors earlier leads to better short- and mid-term outcomes, such as lower death rates after 30 days, fewer ICU admissions, and shorter hospital stays.
- Albumin levels and circulation: Track how blood albumin levels change with circulation status, to see if there's a link with fluid leakage (capillary leak) and risk of death.
- Fluid balance: Analyze how fluid gains and losses relate to changes in heart and circulation measurements.
- Microcirculation: Test if adding signs of small vessel (microcirculation) issues to the main heart and blood flow indicators improves predictions of how patients will do.
- Prediction scores: Investigate whether combining NICaS readings with common scoring systems like SOFA or APACHE helps doctors predict patient outcomes more accurately.
- Time to stability: Compare how quickly patients in each treatment group recover to a stable condition. According to Rosenthal and Kavic's criteria, a patient is considered stable when: -Their illness is improving -There's low risk of getting worse again - Organ support is stable - There's little chance of new problems arising - There are no major complications.
Conclusion This study aims to evaluate whether a more personalized approach using real-time, non-invasive hemodynamic monitoring can lead to better outcomes in septic patients compared to standard care. If successful, this method could help reduce deaths, complications, and treatment costs in sepsis management.
Detailed description
This study is a prospective, multicenter, randomized, open-label, parallel-group interventional trial designed to compare two different strategies for the hemodynamic management of patients with sepsis admitted to medical wards. Participants will be randomly assigned in a 1:1 ratio to either a usual-care strategy or a treatment strategy guided by serial non-invasive hemodynamic monitoring.
The hemodynamic-guided strategy uses the Non-Invasive Cardiac System (NICaS; NI Medical, Petah-Tikva, Israel), an impedance-based non-invasive hemodynamic monitoring device. NICaS provides measurements of several macrohemodynamic parameters, including cardiac index, stroke volume index, cardiac power index, systemic vascular resistance index, and total body water. These measurements are used to characterize the patient's hemodynamic profile and to assess changes following fluid administration and during subsequent treatment.
After enrollment, patients assigned to the hemodynamic-guided group undergo an initial non-invasive hemodynamic assessment followed by a standardized fluid challenge consisting of 10 mL/kg of crystalloid administered over 20 minutes. A subsequent NICaS assessment is performed to evaluate the hemodynamic response to fluid administration, including changes in stroke volume and other hemodynamic parameters. The resulting hemodynamic profile is used to support decisions regarding continuation of fluid therapy and/or initiation or adjustment of vasopressor therapy.
During the first 12 hours after enrollment, serial non-invasive hemodynamic assessments are performed at 180-minute intervals. Based on the evolution of the measured parameters and the patient's clinical condition, fluid and/or vasopressor therapy may be modified with the aim of optimizing the patient's hemodynamic status. Treatment modifications, fluid administration, vasopressor therapy, and relevant clinical parameters are recorded prospectively.
Patients randomized to the usual-care group are managed according to current clinical practice and applicable Surviving Sepsis Campaign recommendations. Fluid resuscitation and subsequent decisions regarding fluid administration and vasopressor therapy are made by the treating physician according to the patient's clinical condition and response to treatment.
In both groups, standardized clinical and laboratory reassessments are performed at predefined time points during the initial days after enrollment. These assessments include vital signs, fluid intake, urine output, blood gas analysis, laboratory parameters, and clinical assessment of organ function. Clinical severity scores are also recorded according to the study protocol. In the hemodynamic-guided group, the serial non-invasive hemodynamic measurements provide additional information to support treatment decisions.
The study will compare the clinical course of patients managed using usual care with that of patients managed using additional serial non-invasive hemodynamic information. In addition to the primary clinical outcome, the study will examine treatment requirements, organ support, fluid balance, vasopressor use, changes in organ dysfunction, and relationships between hemodynamic parameters and other clinical characteristics.
Participants will be followed during hospitalization and for 30 days after enrollment. Vital status and other relevant clinical information will be collected during follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A - Usual Care strategy | Active comparator | Other: Treatment per SSC GuidelinesTreatment per SSC Guidelines Patients receive fluid resuscitation with 30 ml/kg crystalloids over 3 hours. Fluid responsiveness is assessed by blood pressure increase and urine output. Fluid responders (MAP >65 mmHg and urine output >1 ml/kg/h) continue maintenance fluids (1-2 ml/kg/h), adjusted by the physician. Non-fluid responders (MAP ≤65 mmHg or urine output <1 ml/kg/h) start vasopressors to maintain MAP >65 mmHg, with dosage and fluid therapy managed by the physician. All therapy changes are recorded. |
| B - Strategy guided by non-invasive hemodynamic assessment | Experimental | Diagnostic Test: non-invasive hemodynamic assessmentFor patients enrolled in arm B, a non-invasive hemodynamic assessment will be performed using the Non-Invasive Cardiac System (NICaS, NI Medical, Israel). The following parameters will be recorded: cardiac index (CI), stroke volume index (SV), cardiac power index (CPI), systemic vascular resistance index (SVRI), and total body water percentage (TBW). A fluid challenge will then be administered with 10 ml/kg of crystalloids over 20 minutes to assess fluid responsiveness. Hemodynamic response post-fluid challenge will be measured via NICaS. A SV increase >15% defines a "fluid responder" who will continue fluid therapy at 1-2 ml/kg/hr per guidelines. Those with less than 15% SV increase, decreased SVRI, or altered CPI are "fluid non-responders" and will receive vasopressor support, adjusted and recorded accordingly. Hemodynamic evaluations via NICaS will be repeated every 180 minutes for the first 12 hours. Therapy will be adjusted to optimize CI, SV, CPI, SVRI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Provision of specific informed consent;
- Confirmed or suspected diagnosis of sepsis, defined according to the latest SSC guidelines as: "the presence of a clear or suspected infection with life-threatening organ dysfunction caused by a dysregulated host response to infection indicated by a SOFA (Sequential Organ Failure Assessment) score ≥ 2";
- Patients of both sexes, aged 18 years or older;
- Patients evaluated in the Emergency Department for suspected infection requiring hospital admission, at the General Medicine ward of Ospedale Alto Vicentino in Santorso (VI, Italy) or the Emergency Medicine ward of the Policlinico Universitario of Pisa (Italy).
Key exclusion criteria (12 listed)
- Stay in the Emergency Department of more than six hours, considered as the time between ED admission and ward admission;
- Administration of more than 1000 cc of crystalloid therapy in the three hours prior to patient arrival in the ward;
- Any admission from a facility or ward other than the Emergency Department;
- Sepsis related to an ongoing hospital stay or any sepsis not fitting the definition of community-acquired infection;
- Previous hospital admission within four weeks prior to ED access;
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 |
|---|---|---|
| non-invasive hemodynamic assessmentPatients will be evaluated with non-invasive hemodynamic monitoring using NICaS, measuring cardiac index, stroke volume, cardiac power, vascular resistance, and total body water. A fluid challenge (10 ml/kg crystalloids in 20 minutes) will assess fluid responsiveness. Patients with >15% stroke volume increase ("fluid responders") will continue hydration therapy per guidelines. Those with ≤15% increase or altered hemodynamics ("fluid non-responders") will start vasopressor treatment. Hemodynamic monitoring repeats every 3 hours for 12 hours to guide therapy adjustments aiming to optimize key parameters (CI, SV, CPI, SVRI). All treatments, fluid balances, and vital signs are recorded systematically. | Diagnostic test | B - Strategy guided by non-invasive hemodynamic assessment |
| Treatment per SSC GuidelinesPatients receive fluid resuscitation with 30 ml/kg crystalloids over 3 hours. Fluid responsiveness is assessed by blood pressure increase and urine output. Fluid responders (MAP >65 mmHg and urine output >1 ml/kg/h) continue maintenance fluids (1-2 ml/kg/h), adjusted by the physician. Non-fluid responders (MAP ≤65 mmHg or urine output <1 ml/kg/h) start vasopressors to maintain MAP >65 mmHg, with dosage and fluid therapy managed by the physician. All therapy changes are recorded. | Other | A - Usual Care strategy |
Primary outcome
All-cause mortality at 30 days
Time frame: 30 days from hospital admission
The primary endpoint of the study will be all-cause mortality at 30 days from hospital admission. Patient survival will be determined using one of the following methods: review of medical records, phone calls to the patient or their designated contact, or to the healthcare facility.
8 secondary outcomes
Need for organ support
Time frame: From enrollment through hospital discharge
Days free of organ support
Time frame: 30 days after enrollment
Hours free of renal replacement therapy
Time frame: 30 days after enrollment
Initiation of vasopressor therapy
Time frame: From enrollment through hospital discharge
Hours free of vasopressor
Time frame: 30 days after enrollment
Change in SOFA score from baseline
Time frame: From enrollment through hospital discharge, assessed daily
Early mortality
Time frame: 48 hours and 7 days
Length of stay
Time frame: From enrollment through hospital discharge or in-hospital death
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 7 Oct 2026.
- Background: PubMed 32430052Bauer M, Gerlach H, Vogelmann T, Preissing F, Stiefel J, Adam D. Mortality in sepsis and septic shock in Europe, North America and Australia between 2009 and 2019- results from a systematic review and meta-analysis. Crit Care. 2020 May 19;24(1):239. doi: 10.1186/s13054-020-02950-2.
- Background: PubMed 24335434Mayr FB, Yende S, Angus DC. Epidemiology of severe sepsis. Virulence. 2014 Jan 1;5(1):4-11. doi: 10.4161/viru.27372. Epub 2013 Dec 11.
- Background: PubMed 34210173Kingren MS, Starr ME, Saito H. Divergent Sepsis Pathophysiology in Older Adults. Antioxid Redox Signal. 2021 Dec;35(16):1358-1375. doi: 10.1089/ars.2021.0056. Epub 2021 Oct 1.
- Background: PubMed 31954465Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7.
- Background: PubMed 32572531Fleischmann-Struzek C, Mellhammar L, Rose N, Cassini A, Rudd KE, Schlattmann P, Allegranzi B, Reinhart K. Incidence and mortality of hospital- and ICU-treated sepsis: results from an updated and expanded systematic review and meta-analysis. Intensive Care Med. 2020 Aug;46(8):1552-1562. doi: 10.1007/s00134-020-06151-x. Epub 2020 Jun 22.
- Background: PubMed 37975898Fleischmann-Struzek C, Rudd K. Challenges of assessing the burden of sepsis. Med Klin Intensivmed Notfmed. 2023 Dec;118(Suppl 2):68-74. doi: 10.1007/s00063-023-01088-7. Epub 2023 Nov 17.
- Background: PubMed 26903338Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
- Background: PubMed 34599691Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, Machado FR, Mcintyre L, Ostermann M, Prescott HC, Schorr C, Simpson S, Wiersinga WJ, Alshamsi F, Angus DC, Arabi Y, Azevedo L, Beale R, Beilman G, Belley-Cote E, Burry L, Cecconi M, Centofanti J, Coz Yataco A, De Waele J, Dellinger RP, Doi K, Du B, Estenssoro E, Ferrer R, Gomersall C, Hodgson C, Moller MH, Iwashyna T, Jacob S, Kleinpell R, Klompas M, Koh Y, Kumar A, Kwizera A, Lobo S, Masur H, McGloughlin S, Mehta S, Mehta Y, Mer M, Nunnally M, Oczkowski S, Osborn T, Papathanassoglou E, Perner A, Puskarich M, Roberts J, Schweickert W, Seckel M, Sevransky J, Sprung CL, Welte T, Zimmerman J, Levy M. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov;47(11):1181-1247. doi: 10.1007/s00134-021-06506-y. Epub 2021 Oct 2. No abstract available.
- 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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing non-invasive hemodynamic assessment and Treatment per SSC Guidelines in people with Sepsis and Septic Shock, run by Regione del Veneto - AULSS n. 7 Pedemontana at 2 sites in Italy.
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 4 inclusion and 12 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 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. 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 Massimo Marchetti, Dr. (+39 0445571608, massimo.marchetti@aulss7.veneto.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality at 30 days (time frame: 30 days from hospital admission). 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 NCT07863323, which also lists 8 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 7 Oct 2026.