Fluid Responsiveness Evaluation in Sepsis-associated Hypo... | NCT02837731

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment Starling SV monitor	Experimental	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
Control	No Intervention	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Treatment Starling SV monitor	Device	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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 Outcomes

Measure	Description	Time Frame
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

Other Outcomes

Measure	Description	Time Frame
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

Eligibility Module

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	Status	City	State	ZIP	Country	Contacts
University of California San Francisco Medical Center		San Francisco	California	94143	United States

PubMed Identifier	Type	Citation	Retractions
32353418	Derived	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 Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment Starling SV Monitor	During Allocation phase, randomization was a 2:1 allocation of SV-guided to usual care. Subjects that didn't complete Follow-up phase are those that (1) show data that indicates unacceptable bias in the measurements, (2) data collection is interrupted prior to 72 hour data collection period of ICU stay, or (3) severe agitation and/or cardiopulmonary resuscitations resulted in poor quality data. Subjects completed follow-up were included in the Analysis.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Oct 30, 2017	Aug 17, 2020

Arm/Group Information

ID	Title	Description
BG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
BG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

mITT population was predefined as including all patients who signed consent, met study eligibility criteria, were randomized and received monitoring for 72 hours or ICU discharge if earlier. mITT (n=83,41).

Posted

Mean

Standard Deviation

Liters

72 hours

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants	OG00083 OG00141

Title

Denominators

Categories

Title	Measurements
	OG0000.65± 2.85 OG0012.02± 3.44

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.021		Mean Difference (Final Values)	-1.37			2-Sided	95	-2.53	0.21					Superiority

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.

mITT

Posted

Number

percentage of participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts

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.

mITT

Posted

Number

percentage of participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

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.

mITT

Posted

Mean

Standard Deviation

days

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

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).

mITT

Posted

Mean

Standard Deviation

hours

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

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.

mITT

Posted

Mean

Standard Deviation

hours

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

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

mITT

Posted

Mean

Standard Deviation

mg/dL

Baseline, 72 hours

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

Other Pre-specified

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

mITT

Posted

Mean

Standard Deviation

72 hours

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Other Pre-specified

Percentage of Participants With Major Adverse Cardiac Event (MACE)

Incidence of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke.

mITT

Posted

Number

percentage of participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

Other Pre-specified

Number of Participants Experiencing an Adverse Event (AE) Related to Study Device

Adverse events associated with the treatment procedure.

ITT-all randomized.

Posted

Number

participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

Other Pre-specified

Percentage of Participants With Hospital Discharge Without ICU Readmission

mITT

Posted

Number

percentage of participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants	OG000

Other Pre-specified

Percentage of Participants Within Overall 30 Day Mortality Rate

Incidence of death.

mITT

Posted

Number

percentage of participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants	OG000

Other Pre-specified

Number of Participants by Hospital Discharge Location

Patient location (either "home" or "other") following hospital discharge.

mITT

Posted

Count of Participants

Participants

Day 1 to Day 30

ID	Title	Description
OG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.
OG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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) and Starling SV hemodynamic monitor to guide corresponding treatment.	20	102	10	102	0	0
EG001	Usual Care	No required therapeutic protocol will be used for patient treatment, and is determined per the discretion of the physician and hospital standards.	10	48	7	48	0	0

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac Arrest	Cardiac disorders	Other	Systematic Assessment	EG0003 events3 affected102 at risk EG0013 events3 affected48 at risk
Intubation/respiratory distress	Cardiac disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk
Severe septic shock and transition to comfort care	Cardiac disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk
Intubation and ards	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk
Pulmonary edema	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0011 events1 affected48 at risk
Intubation and surgery	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk
Hypoxic Respiratory Failure	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected48 at risk
Respiratory distress requiring intubation and transfer to ICU	Respiratory, thoracic and mediastinal disorders	Other	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected48 at risk
Multiorgan Failure	Metabolism and nutrition disorders	Other	Systematic Assessment	EG0000 events0 affected102 at risk EG0011 events1 affected48 at risk
Skin tear and possible infection related to the monitor leads	Skin and subcutaneous tissue disorders	Other	Systematic Assessment	EG0001 events1 affected102 at risk EG0010 events0 affected48 at risk

ID	Term
D007239	Infections
D018746	Systemic Inflammatory Response Syndrome
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D014652	Vascular Diseases
D002318	Cardiovascular Diseases