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NCT Number: NCT07009665

Fluid Management and Individualized Resuscitation in Sepsis

The goal of this clinical trial is to find out if a personalized treatment approach can improve care for people with sepsis in the emergency department (ED).

Sepsis is a life-threatening condition that happens when the body has an uncontrolled response to an infection. This can lead to low blood pressure, organ failure, and death if not treated quickly. Right now, most people with sepsis receive a standard amount of fluids to raise their blood pressure. But this one-size-fits-all approach can lead to fluid overload and other complications. Because each person responds differently, this study will test whether a more personalized treatment-based on how the heart responds to fluids-can lead to safer and more effective care.

The study will include 188 adults who come to the ED at the University Medical Centre Groningen (UMCG) with suspected sepsis in need of hemodynamic resuscitation. Everyone in the study will receive fluids to support their blood pressure.

Participants will be randomly assigned to one of two groups:

* Personalized treatment group: Fluids and vasopressors (medications that raise blood pressure) will be given based on how the heart responds to each fluid dose. This response is measured using a non-invasive monitor that tracks stroke volume index (ΔSVI)-a measure of how much blood the heart pumps. * Standard care group: Fluids will be given based on current guidelines (30 milliliters per kilogram of body weight), as decided by the treating doctor.

Researchers will compare how much fluid is given during the first 3 hours of care. They will also look at:

* When and how much vasopressor medicine is used * How well blood pressure and circulation respond * Signs of organ recovery or damage * How long participants stay in the hospital * Any problems or side effects during treatment

The researchers hope that this personalized approach will lead to using less fluid, starting vasopressors earlier, and helping people with sepsis recover more safely and quickly.

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Key information

Conditions

Sepsis Critical Care, Fluid Resuscitation Emergency Medicine Fluid Responsiveness Infections Inflammation Pathologic Processes Pathological Conditions, Signs and Symptoms Personalized Medicine Shock Systemic Inflammatory Response Syndrome

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Adult patients (≥ 18 years of age);
  • Referred to internal medicine, nephrology, geriatric medicine, oncology, hematology, lung medicine, rheumatology, gastrointestinal / liver medicine, urology, or emergency medicine (non-trauma);
  • Confirmed or suspected infection according to the physician's judgement upon arrival to the ED, based the presence of an acute phase response not due to an alternative non-infectious cause (i.e., body temperature < 36°C or >38°C, leukocyte count > 12 x109/L or C-reactive protein > 50 mg/L), and/or on symptoms suggestive for an infection (e.g. productive cough, dyspnea, dysuria, pollakisuria, abdominal pain, erythema)
  • Need for hemodynamic resuscitation, based on any of the following (first measurement at ED arrival [triage]):
  • Mean arterial pressure (MAP) < 70 mmHg
  • Systolic blood pressure (SBP) < 90 mmHg or a SBP decrease >40 mmHg
  • Lactate > 4.0 mmol/L
  • Shock index* > 0.9
  • Enrolled in study within one hour after ED arrival

Exclusion criteria

  • Primary diagnosis of: acute cerebral vascular event, acute coronary syndrome, acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, drug overdose, or injury from burn or trauma, diabetic ketoacidosis, hyper-osmolarity syndrome, pancreatitis
  • Known aortic insufficiency, aortic abnormalities, or intraventricular heart defect, such as ventral septal defect or atrial septal defect
  • Known advanced heart failure - meaning NYHA IV functional class HF, on waiting list for heart transplant, LVAD recipient or chronic inotrope use.
  • Known end-stage kidney disease (dialysis-dependent CKD stage 5 or eGFR <15 mL/min/1.73 m²)
  • Decompensated liver cirrhosis at ED admission (e.g., ascites, hepatic encephalopathy, or variceal bleeding)
  • Hemodynamic instability due to active bleeding
  • Patient has received >1 liter of IV fluid prior to study randomization
  • Requires immediate surgery
  • Transfer from another hospital after initiation of therapy (a.o. referred by another hospital ICU) or another in-hospital setting
  • Pregnant women
  • Trauma patients
  • Suspected intra-abdominal hypertension, based on the presence of portal hypertension (i.e. presence of ascites due to liver cirrhosis, esophageal varices or as measured by Doppler ultrasound)
  • Inability to obtain IV access
  • Patient uncouples from treatment algorithm
  • Patient should be excluded based on the opinion of the Clinician/Investigator
  • Not able to commence treatment protocol within 1 hour after randomization
  • Potential ICU-admission unwanted by advanced care directive (e.g., limited life expectancy)

Treatment and study plan

Personalized SV-guided resuscitation

Other

Participants will receive an IV fluid bolus directly after inclusion. Next, measurement of the cardiac output change in response to the fluid bolus by the Starling SV will be used to determine fluid responsiveness. Vital parameters and fluid responsiveness will be used to guide hemodynamic resuscitation, consisting of IV fluids and/or vasopressors, during the first 3 hours.

Standard Care Resuscitation

Other

In the control group, IV fluid and vasopressor administration will be determined at the discretion of the physician and in accordance with currently available guidelines (e.g. Sepsis Surviving Campaign).

Primary outcomes

  1. The volume of IV fluids in ml administered within the first three hours after study enrolment.

    Time frame: Up to three hours, after study enrolment.

    The primary endpoint is the volume of IV fluids in ml administered within the first three hours after study enrolment.

Secondary outcomes

  1. Length-of-stay in hospital/intensive care unit (ICU)

    Time frame: Until hospital discharge, an average of 2 weeks

    Length-of-stay in hospital and on intensive care unit (ICU) in days

  2. New onset organ failure

    Time frame: Up to 48 hours after hospitalization

    Any of the following within 48 hours:

    • Rise in Sequential Organ Failure Assessment (SOFA) score of at least 2
    • Organ support (i.e. vasopressor use [non-]invasive mechanical ventilation, acute dialysis, ECMO)

  3. Fluid balance

    Time frame: Up to three hours after hospitalization

    Net fluid balance calculated as the total volume of fluids administered (intravenous and oral, including prehospital) minus the total volume of fluid output (urine and other measurable losses) within the first three hours after ED presentation

  4. Fluid resuscitation

    Time frame: Up to 7 days after hospitalization

    Volume of IV fluid resusciation within 7 days

  5. Time to recovery of hemodynamic stability

    Time frame: The time interval from hospital admission until hemodynamic stability, measured in hours.

    Hemodynamic stability (HDS) is defined as MAP ≥ 70 mmHg, SBP ≥ 90 mmHg, lactate ≤ 4 mmol/L and SI ≤ 0.9.

  6. Pre-tibial edema development

    Time frame: Up to 48h after hospitalization

    Pre-tibial edema rise of ≥ 2 (grade 1-4), measured at triage, after 3h, 24h and 48h

  7. Fluid overload at three hours (assessed by Point-of-Care Ultrasound)

    Time frame: Up to three hours after hospitalization

    Venous congestion is assessed using Point-of-Care Ultrasound (PoCUS) at three hours after hospital admission. The PoCUS evaluation includes measurements of the Inferior Vena Cava (IVC), the Venous Excess Ultrasound (VExUS) score, and assessment following the Bedside Lung Ultrasound in Emergency (BLUE) protocol.

  8. Fluid overload at 24h (assessed by Point-of-Care Ultrasound)

    Time frame: Up to 24h after hospitalization

    Venous congestion is assessed using Point-of-Care Ultrasound (PoCUS) at 24 hours after hospital admission. The PoCUS evaluation includes measurements of the Inferior Vena Cava (IVC), the Venous Excess Ultrasound (VExUS) score, and assessment following the BLUE protocol.

  9. Loop diuretic use

    Time frame: Up to 7 days after hospitalization

    Loop diuretic use will be determined daily and retrieved from the electronic health records (EHR) of the hospital, general practitioner, and pharmacy.

  10. Decompensated heart failure

    Time frame: Up to 7 days after hospitalization

    Occurrence of decompensated heart failure within 7 days after admission, as determined by the clinical judgment of the treating physician.

  11. Respiratory insufficiency and acute respiratory distress syndrome (ARDS)

    Time frame: Up to 7 days after hospitalization

    ARDS is defined as the presence of any of the following within 7 days after admission:

    • PaO₂/FiO₂ ratio < 53 kPa
    • Requirement for (non-)invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO)

  12. Acute Kidney Injury (AKI within 48 hours)

    Time frame: Up to 48 hours after hospitalization

    AKI is defined according to the KDIGO criteria and assessed within the first 48 hours after admission.

  13. Acute Kidney Injury (AKI within seven days)

    Time frame: Up to 7 days after hospitalization

    AKI is defined according to the KDIGO criteria and assessed within the first seven days after admission.

  14. Change in Serum Creatinine Levels (from Baseline to 48 Hours)

    Time frame: From baseline to 48 hours

    The difference in serum creatinine concentration measured at baseline and at 48 hours after admission.

  15. Change in Serum Creatinine Levels (from baseline to 7 days)

    Time frame: From baseline to 7 days

    The difference in serum creatinine concentration measured at baseline and at 7 days after admission.

  16. Requirement for renal replacement therapy (RRT) within 7 days

    Time frame: Up to 7 days after hospitalization

    Initiation of renal replacement therapy (e.g., hemodialysis, continuous renal replacement therapy) within 7 days after hospital admission, as determined from electronic health care records.

  17. Requirement for renal replacement therapy (RRT) within 30 days

    Time frame: Up to 30 days after hospitalization

    Initiation of renal replacement therapy (e.g., hemodialysis, continuous renal replacement therapy) within 30 days after hospital admission, as determined from electronic health care records.

  18. Major Adverse Cardiac Event (MACE)

    Time frame: Up to 30 days

    Occurrence of any of the following events within 30 days after admission:

    • Cardiovascular death
    • Nonfatal myocardial infarction
    • Nonfatal stroke

  19. Vasopressor initiation within three hours

    Time frame: Up to three hours

    Start of vasopressor therapy within the first three hours after hospital admission.

  20. Vasopressor initiation within 7 days

    Time frame: Up to 7 days

    Start of vasopressor therapy within the first 7 days after hospital admission.

  21. Time to vasopressor initiation

    Time frame: The time interval from hospital admission until the initiation of vasopressor therapy, measured in hours.

    The duration between hospital admission and the initiation of vasopressor treatment.

  22. All-cause mortality (up to 30 days):

    Time frame: Time from hospital admission until death from any cause, up to 30 days

    Mortality will be retrieved from the electronic health records (EHR) from the hospital and municipal registration. The cause of death will be retrieved from the EHR from the hospital.

Other outcomes

  1. Cost-effectiveness

    Time frame: Up to 30 days after hospitalization

    Evaluation of cost-effectiveness based on hospital length of stay, requirement for advanced care, and costs associated with diagnostic and monitoring measurements.

  2. Starling SV monitor trends

    Time frame: Up to three hours after hospitalization

    Continuous monitoring and recording of stroke volume index (SVI), cardiac index (CI), and total peripheral resistance index (TPRI) trends using the Starling SV device throughout the fluid resuscitation period in the intervention group.

  3. Hemodynamic parameter trends

    Time frame: Up to three hours after hospitalization

    Measurement of hemodynamic parameters, including systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, lactate levels, and capillary refill time, during resuscitation period, recorded up to three hours after arrival at the emergency department.

  4. Photoplethysmographic (PPG) waveform trends

    Time frame: Up to three hours after hospitalization

    Measurement of photoplethysmography (PPG) waveform features, including systolic and diastolic peak amplitudes, pulse interval and perfusion index, recorded continuously during the emergency department stay, up to three hours after arrival.

  5. Electrocardiography (ECG) waveform trends

    Time frame: Up to three hours after hospitalization

    Measurement of Electrocardiography (ECG) waveform features, including pulse transit time (PTT) and heart rate variability (HRV), recorded continuously during the emergency department stay, up to three hours after arrival.

Study contacts

Contact information is provided by the study sponsor or research team.

Sanne Ter Horst, MD

CONTACT

[email protected]

+31 6 25650284 (FLUIDS phone)

Sanne Ter Horst, MD

CONTACT

[email protected]

Sponsors and collaborators

Lead sponsor

University Medical Center Groningen

Other

Registry information

Acronym: FLUIDS

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jun 6, 2025
Registry last updated
Dec 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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