Venous Excess Ultrasound for Personalized Resuscitation in Septic Shock (VESPER)

Venous Excess Ultrasound (VEXUS)-Guided Management Versus Usual Care in Patients with Septic Shock: a Pilot Randomized Controlled Trial

The goal of this pilot clinical trial is to determine if conducting a larger study using venous excess ultrasound (VEXUS) to guide fluid management in patients with septic shock is feasible. Septic shock is a life-threatening condition where infection causes dangerously low blood pressure. While fluids are essential for treatment, too much fluid can harm the kidneys and result in the need for dialysis. The main questions it aims to answer are:

1. Is it feasible to recruit patients, obtain consent, and follow the VEXUS-guided management protocol?
2. Does VEXUS-guided management, compared with usual care, improve the health and well-being of patients with septic shock?

Researchers will compare two groups: one receiving VEXUS-guided fluid management versus another receiving standard care, to assess the feasibility of a larger trial and explore whether VEXUS prevents fluid overload and kidney problems.

Participants in the VEXUS group will:

1. Undergo VEXUS scans every 24 hours for 3 days
2. Receive fluid management guided by VEXUS findings (including fluid restriction or removal if we identify venous congestion) and undergo cardiac ultrasound if we identify moderate to severe congestion
3. Be monitored for 28 days to track kidney function, need for dialysis, and survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Sepsis; Shock; Septic Shock; Resuscitation; Critical Care, Intensive Care
• Intervention / Treatment: Other: Venous Excess Ultrasound (VEXUS)-Guided Management

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: John Basmaji, MD; Phone Number: 55661 1-519-685-8500; Email: John.basmaji@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • London Health Sciences Center
      • Contact: John Basmaji, MD; Phone Number: 55661 1-519-685-8500; Email: John.basmaji@lhsc.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adult patients (≥18 years)
2. Within 12 hours of meeting septic shock diagnosis based on following Sepsis-3 criteria: requirement for vasopressors to maintain organ perfusion, lactate > 2 mmol/L, and suspected or confirmed infection)
3. Within 48 hours of intensive care unit admission.

Exclusion Criteria:

1. Already receiving renal replacement therapy
2. Patients for whom a decision to initiate renal replacement therapy has been made prior to study enrolment
3. Patients who have limitations on medical therapy or restrictions on goals of care
4. Active bleeding causing hemodynamic instability
5. Veno-venous or veno-arterial extracorporeal membrane oxygenation
6. Previously enrolment in study
7. 10% or more of body surface area acute burn injury
8. Suspected or confirmed liver cirrhosis
9. Established allergy to sulfa drugs;
10. Patients receiving treatments that require continuous IV fluid infusions (e.g., diabetic ketoacidosis, diabetes insipidus)
11. Unable to measure fluid balance accurately
12. Contra-indication to study recommended interventions (e.g., diuretics, inotropes)
13. Unable to perform VEXUS due to anatomical barriers (e.g., surgical dressings);
14. Unable to complete VEXUS scan during the 6-hour resuscitation window
15. Moderate to Severe Tricuspid Regurgitation
16. Untreated Metabolic/biochemical findings (Hypokalemia [K+]< 3.0 mmol/L; metabolic alkalosis [Bicarbonate > 40 mmol/L and/or pH > 7.55], Hypomagnesemia [Mg2+] < 0.6, and Hypernatremia [Na+] > 155 mmol/L)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venous Excess Ultrasound (VEXUS)-Guided Management	Other: Venous Excess Ultrasound (VEXUS)-Guided Management; Expert operators will perform VEXUS within 6 hours of randomization and repeat the assessment every 24 hours for 3 days, or until ICU discharge or death. After each assessment, investigators will grade the severity of venous congestion using a modified version of the VEXUS score and provide updated management recommendations. Patients without congestion will receive standard fluid management. For mild congestion, investigators will implement fluid restriction (e.g., minimizing maintenance fluids) while maintaining nutrition and blood product administration as clinically indicated. For moderate to severe congestion, investigators will 1. target negative fluid balance (-1 to -2L/24h) through fluid restriction and diuretics, 2. perform cardiac ultrasound to guide inotrope administration and optimize RV physiology, and 3. optimize PEEP for ventilated patients. All patients will receive the standard of care based on Surviving Sepsis Campaign guidelines.
No Intervention: Control Arm; Investigators will provide patients with the standard of care according to the Surviving Sepsis Campaign guidelines. This includes fluid resuscitation, the recommended mean arterial pressure target of ≥65 mmHg, early broad-spectrum antibiotics, source control when applicable, vasopressor support with norepinephrine as the first-line agent, stress-dose corticosteroids, early nutrition, and lung-protective mechanical ventilation when required. Clinicians may utilize hemodynamics assessment tools such as dynamic measures of fluid responsiveness and point-of-care ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	Number of participants enrolled during the recruitment period who successfully complete study procedures and follow-up.	Up to 160 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consent rate	The total number of eligible participants consented divided by the total number of eligible participants approached for consent.	From enrollment to the end of the study period at 28 days
VEXUS scan completion rate	The number of participants who successfully undergo a VEXUS scan and, if applicable, cardiac evaluation, divided by the total number of participants randomized to the intervention arm.	From enrollment to the end of treatment period at 3 days
Protocol Adherence	Intervention arm: For fluid balance adherence, we will calculate the proportion of participants who achieved the protocol-specified fluid balance targets on days 1 to 3, divided by the total number of participants in the intervention arm. This metric will account for participants who withdraw or deviate from the protocol. To assess adherence to inotrope initiation based on POCUS findings, we will determine the percentage of participants who received inotropes when indicated by POCUS results, as per protocol guidelines, divided by the total number of participants with POCUS findings warranting inotrope initiation. Control arm: The number of participants in the control arm who do NOT receive a VEXUS scan during the 28-day study period (or until ICU discharge or death) divided by the total number randomized to this arm.	From enrollment to the end of treatment period at 3 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Metabolic abnormalities: hypokalemia < 3.0 mmol/L; hyponatremia <130 mmol/L, or hypernatremia > 155 mmol/L, metabolic alkalosis pH>7.55 or bicarbonate >40 mmol/L, and hypomagnesemia < 0.6 mmol/L) Hemodynamic events: hypotension episodes (defined as mean arterial pressure < 60 mmHg for 5 minutes or more), hypotension episodes requiring intervention (greater than 20% increase in vasopressor requirements from baseline or need for fluid bolus), tachyarrhythmias Organ Injury: acute kidney injury All adverse events will be reported daily for days 1 to 3	From enrollment to the end of treatment period at 3 days
28-Day Mortality		From enrollment to 28 days
90-Day Mortality		From enrollment to 90 days
Duration of Vasoactive Medication	Defined as the time from initiation to the first successful discontinuation of vasopressors and inotropes, where successful discontinuation means no reinitiation for at least 12 consecutive hours	From enrollment to the discontinuation of vasoactive medication, assessed up to 52 weeks
Days alive and free of vasoactive medications at 28 days		From enrollment to 28 days
Duration of mechanical ventilation	Defined as the time from initiation to the first successful liberation of mechanical ventilation, where successful liberation means no reinitiation of mechanical ventilation for at least 12 consecutive hours	From enrollment to the discontinuation of mechanical ventilation, assessed up to 52 weeks
Days alive and free of mechanical ventilation at 28 days		From enrollment to 28 days
Need for Renal Replacement Therapy	Proportion of patients who require renal replacement therapy at 28 days	From enrollment to 28 days
Days alive and free of renal replacement therapy at 28 days		From enrollment to 28 days

Collaborators and Investigators

• Sponsor: Western University, Canada
• Collaborators: London Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2024
• Primary Completion (Estimated): December 28, 2027
• Study Completion (Estimated): December 28, 2027

Study Registration Dates

• First Submitted: November 14, 2024
• First Submitted That Met QC Criteria: November 18, 2024
• First Posted (Estimated): November 20, 2024

Study Record Updates

• Last Update Posted (Estimated): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Ultrasound; Randomized Controlled Trial; Septic Shock; Resuscitation; Pilot Study; Venous Congestion
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic
• Other Study ID Numbers: 125708

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No