Fluid Responsiveness Evaluation in Sepsis-associated Hypotension

Study Overview
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Brief Summary
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This study assesses the mean difference in fluid balance at ICU discharge and associated patient outcomes, based on a dynamic assessment of fluid responsiveness in septic patients with refractory hypotension in an ICU setting.

Detailed Description
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Multi-center randomized study comparing dynamic assessment of fluid responsiveness utilizing Starling SV monitor compared to a control group. Subjects will be randomized in a 2:1 treatment to control group ratio to increase power for sub-analysis by patient population. Patients randomized to the Starling SV arm will have treatment guided by a dynamic assessment of fluid responsiveness (measured by a change in stroke volume index > 10%) as assessed by passive leg raise (PLR). Patients randomized to the control group will receive standard of care treatment.

Official Title
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Evaluation of Fluid Volume in Patients With Sepsis and Refractory Hypotension

Conditions
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Hypotension, Sepsis

Intervention / Treatment
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* Device: Treatment Starling SV monitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of sepsis, as exhibited by 2 or more of the following systemic inflammatory response syndrome (SIRS) criteria and a known or presumed infection at time of screening: Temperature of > 38 C or < 36 C Heart rate of > 90/min Respiratory rate of > 20/min or PaCO2 < 32 mm Hg (4.3 kPA) White blood cell count > 12000/mm3 or < 4000/mm3 or >10% immature bands Refractory hypotension despite initial fluid resuscitation (1L of treatment fluid) Patient enrolled in study as soon as possible (ideal window of 0-12 hours) and within 24 hours of arrival to the hospital Anticipated ICU admission Able to provide signed informed consent or consent can be obtained from the patient's authorized representative 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 Known aortic insufficiency, or aortic abnormalities Hemodynamic instability due to active gastrointestinal hemorrhage Patient has received >3 liters of IV fluid prior to study randomization Requires immediate surgery Patient transferred to the ICU from another hospital unit Do not attempt resuscitation (DNAR or DNR) order Advanced directives restricting implementation of the resuscitation protocol Contraindication to blood transfusion Attending clinician deems aggressive resuscitation unsuitable Transferred from another in-hospital setting Not able to commence treatment protocol within 1 hour after randomization Known intraventricular heart defect, such as ventral septal defect or atrial septal defect Use of additional hemodynamic monitoring involving stroke volume variation (SVV) to determine fluid responsiveness Seizure in the last 24 hours Prisoner Pregnancy Age <18 Known allergy to sensor material or gel Inability or contraindication to doing a passive leg raise with both extremities, such as inability to interrupt venous compression boots Patient has an epidural catheter in place Suspected intra-abdominal hypertension Inability to obtain IV access Diabetic ketoacidosis Hyper-osmolarity syndrome Patient uncouples from treatment algorithm Patient should be excluded based on the opinion of the Clinician/Investigator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Starling SV monitor<br>A dynamic assessment of fluid responsiveness using the Starling SV monitor will be performed at every clinical decision point for the first 72 hours of study enrollment. Examples of a clinical decision point include a mean arterial pressure (MAP) of < 65, the decision to give additional fluid volume, and the decision to either escalate or wean vasopressors. Fluid responsiveness will be assessed using a passive leg raise (PLR) to guide corresponding treatment. | Device: Treatment Starling SV monitor<br>* A dynamic assessment of fluid responsiveness will be performed at every clinical decision point for the first 72 hours of study enrollment. Fluid responsiveness will be assessed using a passive leg raise (PLR) and Starling SV hemodynamic monitor to guide corresponding treatment.<br>|
| No Intervention: Control<br>No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid Balance | Fluid balance is defined as all intravenous fluids administered over a 72 hour period (or ICU discharge, whichever occurred first), minus all fluid output. Urine output was measured in the ICU in 12 hour increments. | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Requiring Renal Replacement Therapy | Renal replacement therapy (RRT) is therapy that replaces the normal blood-filtering function of the kidneys. It is used when the kidneys are not working well, which is called kidney failure and includes acute kidney injury and chronic kidney disease. Patient receives new treatment with dialysis. | Day 1 to Day 30 | 
| Percentage of Participants Requiring Ventilator Use | Patients did not enter the study on ventilation, but required ventilator use during the study are included in the analysis. | Day 1 to Day 30 | 
| Length of ICU Stay | Intensive Car Unit (ICU) length of stay will be calculated using the earliest of date that the subject is medically ready for discharge when captured, the date of discharge, or the study exit date. | Day 1 to Day 30 | 
| Number of Hours of Ventilator Use | Patients that did not enter the study on ventilation, but required ventilator use during the study are included in the analysis.Ventilator use might have improved (less use of ventilator support), had no change, or worsened (more use of ventilator support). | Day 1 to Day 30 | 
| Number of Hours of Vasopressor Use | Vasopressor drugs are provided to restore and maintain blood pressure in patients with septic shock. Patients that have vasopressors initiated throughout the trial are included in this analysis. | Day 1 to Day 30 | 
| Change From Baseline in Serum Creatinine Levels at 72 Hours | The diagnosis of Acute Kidney Injury (AKI) is traditionally based on a rise in serum creatinine | Baseline, 72 hours |