Fluid Responsiveness Evaluation in Sepsis-associated Hypotension

Sepsis Clinical Trial

— FRESH  

Official title:

Evaluation of Fluid Volume in Patients With Sepsis and Refractory Hypotension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02837731
• Other study ID #: PRO-OOO1
• Status: Completed
• Phase: N/A
• Start date: October 2016
• Est. completion date: March 13, 2019

Study information

• Verified date: November 2020
• Source: Baxter Healthcare Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: March 13, 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hypotension
• Sepsis
• Toxemia

Intervention

Device:
• Treatment Starling SV monitor
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.

Locations

Country	Name	City	State
United Kingdom	Royal Surrey County Hospital	Guildford
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Ohio State University Hospital	Columbus	Ohio
United States	Denver Health	Denver	Colorado
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Methodist Hospital	Indianapolis	Indiana
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	New York Presbyterian Brooklyn Methodist Hospital	New York	New York
United States	NYU School of Medicine	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California San Francisco Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Cheetah Medical Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Volume of Fluid	Traditional methods of assessing fluid responsiveness (FR) such as vital signs, physical examination, and static measurements of circulatory pressure have shown not to reliably correlate with fluid responsiveness. In contrast, dynamic measurement of stroke volume (SV) following an intravenous (IV) fluid bolus or passive leg raise (PLR) is a safe and feasible method of rapidly assessing the effectiveness of fluid-induced augmentation of SV and cardiac output (CO). Mean volume of treatment fluid Administered (ml) at 72 hours or ICU discharge, whichever occurs first, between the two treatment groups	72 hours
Other	Percentage of Participants With Major Adverse Cardiac Event (MACE)	Incidence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.	Day 1 to Day 30
Other	Number of Participants Experiencing an Adverse Event (AE) Related to Study Device	Adverse events associated with the treatment procedure.	Day 1 to Day 30
Other	Percentage of Participants With Hospital Discharge Without ICU Readmission		Day 1 to Day 30
Other	Percentage of Participants Within Overall 30 Day Mortality Rate	Incidence of death.	Day 1 to Day 30
Other	Number of Participants by Hospital Discharge Location	Patient location (either "home" or "other") following hospital discharge.	Day 1 to Day 30
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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