Fluid Responsiveness Evaluation in Sepsis-associated Hypotension

Not Applicable

Completed

• Conditions: Sepsis; Hypotension
• Interventions: Device: Treatment Starling SV monitor

• Registration Number: NCT02837731
• Lead Sponsor: Cheetah Medical Inc.

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2016-07-14
• Study First Submitted QC: 2016-07-15
• Study First Posted: 2016-07-20
• Study Start: 2016-10
• Primary Completion: 2019-03
• Study Completion: 2019-03-13
• Results First Submitted: 2020-08-17
• Status Verified: 2020-11
• Results First Submitted QC: 2020-11-10
• Last Update Submitted: 2020-11-10
• Results First Posted: 2020-12-03
• Last Update Posted: 2020-12-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. 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

2. Refractory hypotension despite initial fluid resuscitation (1L of treatment fluid)

3. Patient enrolled in study as soon as possible (ideal window of 0-12 hours) and within 24 hours of arrival to the hospital

4. Anticipated ICU admission

5. Able to provide signed informed consent or consent can be obtained from the patient's authorized representative

Exclusion Criteria

1. 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
2. Known aortic insufficiency, or aortic abnormalities
3. Hemodynamic instability due to active gastrointestinal hemorrhage
4. Patient has received >3 liters of IV fluid prior to study randomization
5. Requires immediate surgery
6. Patient transferred to the ICU from another hospital unit
7. Do not attempt resuscitation (DNAR or DNR) order
8. Advanced directives restricting implementation of the resuscitation protocol
9. Contraindication to blood transfusion
10. Attending clinician deems aggressive resuscitation unsuitable
11. Transferred from another in-hospital setting
12. Not able to commence treatment protocol within 1 hour after randomization
13. Known intraventricular heart defect, such as ventral septal defect or atrial septal defect
14. Use of additional hemodynamic monitoring involving stroke volume variation (SVV) to determine fluid responsiveness
15. Seizure in the last 24 hours
16. Prisoner
17. Pregnancy
18. Age <18
19. Known allergy to sensor material or gel
20. Inability or contraindication to doing a passive leg raise with both extremities, such as inability to interrupt venous compression boots
21. Patient has an epidural catheter in place
22. Suspected intra-abdominal hypertension
23. Inability to obtain IV access
24. Diabetic ketoacidosis
25. Hyper-osmolarity syndrome
26. Patient uncouples from treatment algorithm
27. Patient should be excluded based on the opinion of the Clinician/Investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Starling SV monitor	Treatment Starling SV monitor	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.

Primary Outcome Measures

Name	Time	Method
Fluid Balance	72 hours	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Requiring Renal Replacement Therapy	Day 1 to Day 30	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.
Percentage of Participants Requiring Ventilator Use	Day 1 to Day 30	Patients did not enter the study on ventilation, but required ventilator use during the study are included in the analysis.
Number of Hours of Ventilator Use	Day 1 to Day 30	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).
Number of Hours of Vasopressor Use	Day 1 to Day 30	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.
Length of ICU Stay	Day 1 to Day 30	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.
Change From Baseline in Serum Creatinine Levels at 72 Hours	Baseline, 72 hours	The diagnosis of Acute Kidney Injury (AKI) is traditionally based on a rise in serum creatinine

Trial Locations

Locations (12)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Royal Surrey County Hospital; 🇬🇧 Guildford, United Kingdom

Grady Memorial Hospital; 🇺🇸 Atlanta, Georgia, United States

Indiana University Methodist Hospital; 🇺🇸 Indianapolis, Indiana, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

New York Presbyterian Brooklyn Methodist Hospital; 🇺🇸 New York, New York, United States

Ohio State University Hospital; 🇺🇸 Columbus, Ohio, United States

Denver Health; 🇺🇸 Denver, Colorado, United States

University of California San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

NYU School of Medicine; 🇺🇸 New York, New York, United States

Rhode Island Hospital; 🇺🇸 Providence, Rhode Island, United States