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Fluid Responsiveness Evaluation in Sepsis-associated Hypotension (FRESH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02837731
Recruitment Status : Completed
First Posted : July 20, 2016
Results First Posted : December 3, 2020
Last Update Posted : December 3, 2020
Information provided by (Responsible Party):
Baxter Healthcare Corporation ( 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.

Condition or disease Intervention/treatment Phase
Sepsis Hypotension Device: Treatment Starling SV monitor Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Fluid Volume in Patients With Sepsis and Refractory Hypotension
Actual Study Start Date : October 2016
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 13, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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.
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.

No Intervention: Control
No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Primary Outcome Measures :
  1. Fluid Balance [ Time Frame: 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 :
  1. Percentage of Participants Requiring Renal Replacement Therapy [ Time Frame: 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.

  2. Percentage of Participants Requiring Ventilator Use [ Time Frame: 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.

  3. Length of ICU Stay [ Time Frame: 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.

  4. Number of Hours of Ventilator Use [ Time Frame: 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).

  5. Number of Hours of Vasopressor Use [ Time Frame: 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.

  6. Change From Baseline in Serum Creatinine Levels at 72 Hours [ Time Frame: Baseline, 72 hours ]
    The diagnosis of Acute Kidney Injury (AKI) is traditionally based on a rise in serum creatinine

Other Outcome Measures:
  1. Volume of Fluid [ Time Frame: 72 hours ]
    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

  2. Percentage of Participants With Major Adverse Cardiac Event (MACE) [ Time Frame: Day 1 to Day 30 ]
    Incidence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

  3. Number of Participants Experiencing an Adverse Event (AE) Related to Study Device [ Time Frame: Day 1 to Day 30 ]
    Adverse events associated with the treatment procedure.

  4. Percentage of Participants With Hospital Discharge Without ICU Readmission [ Time Frame: Day 1 to Day 30 ]
  5. Percentage of Participants Within Overall 30 Day Mortality Rate [ Time Frame: Day 1 to Day 30 ]
    Incidence of death.

  6. Number of Participants by Hospital Discharge Location [ Time Frame: Day 1 to Day 30 ]
    Patient location (either "home" or "other") following hospital discharge.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02837731

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United States, California
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
United States, Colorado
Denver Health
Denver, Colorado, United States, 80204
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
United States, Indiana
Indiana University Methodist Hospital
Indianapolis, Indiana, United States, 46202
United States, New York
NYU School of Medicine
New York, New York, United States, 10016
New York Presbyterian Brooklyn Methodist Hospital
New York, New York, United States, 11215
United States, Ohio
Ohio State University Hospital
Columbus, Ohio, United States, 43210
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
United Kingdom
Royal Surrey County Hospital
Guildford, United Kingdom
Sponsors and Collaborators
Cheetah Medical Inc.
  Study Documents (Full-Text)

Documents provided by Baxter Healthcare Corporation ( Cheetah Medical Inc. ):
Study Protocol  [PDF] October 30, 2017
Statistical Analysis Plan  [PDF] June 28, 2018

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Cheetah Medical Inc. Identifier: NCT02837731    
Other Study ID Numbers: PRO-OOO1
First Posted: July 20, 2016    Key Record Dates
Results First Posted: December 3, 2020
Last Update Posted: December 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Summary data will be reviewed periodically

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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
Additional relevant MeSH terms:
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Systemic Inflammatory Response Syndrome
Pathologic Processes
Vascular Diseases
Cardiovascular Diseases