Clinical trial NCT02837731: Fluid Responsiveness Evaluation in Sepsis-associated Hypotension
Official title: Evaluation of Fluid Volume in Patients With Sepsis and Refractory Hypotension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sepsis
Hypotension
Lead sponsor: Baxter Healthcare Corporation
Sponsor class: INDUSTRY
First posted: 2016-07-20
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fluid Balance
timeFrame: 72 hours
Secondary outcomes:
measure: Percentage of Participants Requiring Renal Replacement Therapy
timeFrame: Day 1 to Day 30
measure: Percentage of Participants Requiring Ventilator Use
timeFrame: Day 1 to Day 30
measure: Length of ICU Stay
timeFrame: Day 1 to Day 30
measure: Number of Hours of Ventilator Use
timeFrame: Day 1 to Day 30
measure: Number of Hours of Vasopressor Use
timeFrame: Day 1 to Day 30
measure: Change From Baseline in Serum Creatinine Levels at 72 Hours
timeFrame: Baseline, 72 hours
Other outcomes:
measure: Volume of Fluid
timeFrame: 72 hours
measure: Percentage of Participants With Major Adverse Cardiac Event (MACE)
timeFrame: Day 1 to Day 30
measure: Number of Participants Experiencing an Adverse Event (AE) Related to Study Device
timeFrame: Day 1 to Day 30
measure: Percentage of Participants With Hospital Discharge Without ICU Readmission
timeFrame: Day 1 to Day 30
measure: Percentage of Participants Within Overall 30 Day Mortality Rate
timeFrame: Day 1 to Day 30
measure: Number of Participants by Hospital Discharge Location
timeFrame: Day 1 to Day 30
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Denver
country: United States
facility: Denver Health
state: Colorado
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Methodist Hospital
state: Indiana
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: New York
country: United States
facility: New York Presbyterian Brooklyn Methodist Hospital
state: New York
city: Columbus
country: United States
facility: Ohio State University Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
Study officials:
References:
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.