Back to resultsFluid Responsiveness Evaluation in Sepsis-associated Hypotension (FRESH)
Primary Purpose
Sepsis, Hypotension
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Treatment Starling SV monitor
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis
Eligibility Criteria
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
Sites / Locations
- University of California San Francisco Medical Center
- Denver Health
- Grady Memorial Hospital
- Indiana University Methodist Hospital
- NYU School of Medicine
- New York Presbyterian Brooklyn Methodist Hospital
- Ohio State University Hospital
- Oregon Health and Science University
- Rhode Island Hospital
- Vanderbilt University Medical Center
- Baylor College of Medicine
- Royal Surrey County Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Treatment Starling SV monitor
Control
Arm Description
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.
No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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).
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.
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02837731
Brief Title
Fluid Responsiveness Evaluation in Sepsis-associated Hypotension
Acronym
FRESH
Official Title
Evaluation of Fluid Volume in Patients With Sepsis and Refractory Hypotension
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
October 2016 (Actual)
Primary Completion Date
March 2019 (Actual)
Study Completion Date
March 13, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cheetah Medical Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Hypotension
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Starling SV monitor
Arm Type
Experimental
Arm Description
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.
Arm Title
Control
Arm Type
No Intervention
Arm Description
No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.
Intervention Type
Device
Intervention Name(s)
Treatment Starling SV monitor
Intervention Description
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.
Primary Outcome Measure Information:
Title
Fluid Balance
Description
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.
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Percentage of Participants Requiring Renal Replacement Therapy
Description
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.
Time Frame
Day 1 to Day 30
Title
Percentage of Participants Requiring Ventilator Use
Description
Patients did not enter the study on ventilation, but required ventilator use during the study are included in the analysis.
Time Frame
Day 1 to Day 30
Title
Length of ICU Stay
Description
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.
Time Frame
Day 1 to Day 30
Title
Number of Hours of Ventilator Use
Description
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).
Time Frame
Day 1 to Day 30
Title
Number of Hours of Vasopressor Use
Description
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.
Time Frame
Day 1 to Day 30
Title
Change From Baseline in Serum Creatinine Levels at 72 Hours
Description
The diagnosis of Acute Kidney Injury (AKI) is traditionally based on a rise in serum creatinine
Time Frame
Baseline, 72 hours
Other Pre-specified Outcome Measures:
Title
Volume of Fluid
Description
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
Time Frame
72 hours
Title
Percentage of Participants With Major Adverse Cardiac Event (MACE)
Description
Incidence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.
Time Frame
Day 1 to Day 30
Title
Number of Participants Experiencing an Adverse Event (AE) Related to Study Device
Description
Adverse events associated with the treatment procedure.
Time Frame
Day 1 to Day 30
Title
Percentage of Participants With Hospital Discharge Without ICU Readmission
Time Frame
Day 1 to Day 30
Title
Percentage of Participants Within Overall 30 Day Mortality Rate
Description
Incidence of death.
Time Frame
Day 1 to Day 30
Title
Number of Participants by Hospital Discharge Location
Description
Patient location (either "home" or "other") following hospital discharge.
Time Frame
Day 1 to Day 30
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University of California San Francisco Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Denver Health
City
Denver
State/Province
Colorado
ZIP/Postal Code
80204
Country
United States
Facility Name
Grady Memorial Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
Indiana University Methodist Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
NYU School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
New York Presbyterian Brooklyn Methodist Hospital
City
New York
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
Ohio State University Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Royal Surrey County Hospital
City
Guildford
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Summary data will be reviewed periodically
Citations:
PubMed Identifier
32353418
Citation
Douglas IS, Alapat PM, Corl KA, Exline MC, Forni LG, Holder AL, Kaufman DA, Khan A, Levy MM, Martin GS, Sahatjian JA, Seeley E, Self WH, Weingarten JA, Williams M, Hansell DM. Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial. Chest. 2020 Oct;158(4):1431-1445. doi: 10.1016/j.chest.2020.04.025. Epub 2020 Apr 27.
Results Reference
derived
Learn more about this trial
Fluid Responsiveness Evaluation in Sepsis-associated Hypotension
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