Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator

Shock, Septic Clinical Trial

Official title:

Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06426407
• Other study ID #: 21-047
• Status: Not yet recruiting
• Start date: June 2024
• Est. completion date: January 2026

Study information

• Verified date: May 2024
• Source: The Cleveland Clinic
• Contact: Seth Bauer, PharmD
• Phone: 2169522553
• Email: bauers[@]ccf.org
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to learn about blood pressure response to the vasopressor drug vasopressin in people with septic shock.

The main questions it aims to answer are:

• Are the levels of molecules showing communication between cells different between people whose blood pressure improves and people whose blood pressure does not improve when given a vasopressor medication?

• Are measurements found on echocardiography (heart ultrasound) different between people whose blood pressure improves and people whose blood pressure does not improve when given a vasopressor medication?

Participants will be asked to contribute one or two blood samples. Participants who are ordered the drug vasopressin will contribute two blood samples. Both samples will be about two tablespoons for a total of about four tablespoons. One sample will be drawn before starting vasopressin infusion and the second sample will be drawn between one and six hours after starting the vasopressor drug infusion. At the same time points, advanced echocardiography pictures will be taken. Participants who are not ordered the drug vasopressin and only ordered the drug norepinephrine will contribute only one sample. At the time the sample is collected, advanced echocardiography pictures will be taken. This research also involves analyzing data obtained during the participant's hospital stay.

Description:

Septic shock mortality remains high at 33% in North America; current clinical predictors of poor outcomes in septic shock are suboptimal. In addition to antibiotics and intravenous fluids, vasoactive agents are initiated to restore effective tissue perfusion. Norepinephrine (NE) is the recommended first-line vasopressor, but adjunctive arginine vasopressin is used in over one-third of patients to improve blood pressure or decrease NE dosage. However, less than half of vasopressin recipients have a clinically-apparent hemodynamic response (defined as a decrease in NE dosage at 6 hours after vasopressin initiation). Vasopressors, particularly norepinephrine, are known to be immune modulators. Further, each vasopressor has its own unique effect on a patient's hemodynamic profile as assessed by echocardiography. In the current study, the investigators seek to clarify the link between vasopressin, immune response, and hemodynamic profile. The central goal of this proposal is to identify "vasopressin response" as an easily-identifiable bedside indicator of a distinct septic shock subphenotype.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 48
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (=18 years old)

• Septic shock (as defined by Sepsis-3)

• Receiving norepinephrine

• Admitted to a medical, surgical, NeuroSciences, or mixed intensive care unit

• Central venous catheter in place

• Ordered fixed-dose vasopressin as an adjunct to norepinephrine by the primary care team (unless in active control cohort)

Exclusion Criteria:

• Vasopressin ordered for an indication other than septic shock

• Vasopressin initiated at another institution

• Receiving a primary vasopressor other than norepinephrine (eg, phenylephrine)

• Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the preceding 28 days

• Blood hemoglobin concentration <7 g/dL

• Primary treatment team determines that vasopressin initiation is emergent

• Patient or their legal authorized representative opts to not participate in the study

Related Conditions & MeSH terms

• Shock
• Shock, Septic

Intervention

Drug:
• Vasopressin
Fixed dosage vasopressin ordered as an adjunctive vasopressor to norepinephrine

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Plasma interleukin-1ß (IL-1ß) concentration	Compare plasma interleukin-1ß (IL-1ß) concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma interleukin-6 (IL-6) concentration	Compare plasma interleukin-6 (IL-6) concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma interferon-gamma (IFN-?) concentration	Compare plasma interferon-gamma (IFN-?) concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma C-X-C motif chemokine ligand 10 (CXCL10, also known as interferon gamma-induced protein 10 [IP-10]) concentration	Compare plasma C-X-C motif chemokine ligand 10 (CXCL10, also known as interferon gamma-induced protein 10 [IP-10]) concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma granulocyte-colony stimulating factor (G-CSF) concentration	Compare plasma granulocyte-colony stimulating factor (G-CSF) concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma E-selectin concentration	Compare plasma E-selectin concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma vasopressin concentration	Evaluate the association of plasma vasopressin concentration with ratio of plasma interleukin-10 (IL-10) to tumor necrosis factor-a (TNF-a) over time. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Plasma copeptin concentration	Compare plasma copeptin concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Left ventricular ejection fraction (LVEF) change	Compare left ventricular ejection fraction (LVEF) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Stroke volume (SV) by echocardiography	Compare stroke volume (SV) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Tricuspid annular plane systolic excursion (TAPSE)	Compare tricuspid annular plane systolic excursion (TAPSE) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Tricuspid annular systolic plane velocity (TAPSV, also known as RV S')	Compare tricuspid annular systolic plane velocity (TAPSV, also known as RV S') over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Venous-arterial carbon dioxide tension gradient (Pva-CO2)	Compare venous-arterial carbon dioxide tension gradient (Pva-CO2) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Central venous oxygen saturation (ScvO2)	Compare central venous oxygen saturation (ScvO2) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Dynamic arterial elastance (Eadyn, the ratio of pulse pressure variation to stroke volume variation)	Compare dynamic arterial elastance (Eadyn) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other	Clinical trajectory	Compare the ordinal outcome clinical trajectory (comprised of rapid recovery, chronic critical illness, and early recovery) between vasopressin responders vs. non-responders.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through the sooner of intensive care unit discharge or 14 days.
Other	Incidence of in-hospital mortality	Compare the incidence of hospital mortality in vasopressin responders vs. non-responders.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through hospital discharge.
Other	Intensive care unit length of stay	Compare intensive care unit length of stay in vasopressin responders vs. non-responders.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through intensive care unit discharge.
Primary	Ratio of plasma interleukin-10 (IL-10) to tumor necrosis factor-a (TNF-a)	Compare baseline ratio of plasma concentrations of interleukin-10 (IL-10) to tumor necrosis factor-a (TNF-a) in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement).
Secondary	Left ventricular ejection fraction (LVEF)	Compare baseline left ventricular ejection fraction (LVEF) in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement).
Secondary	Ratio of ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees)	Compare left ventricular-arterial coupling (ratio of arterial elastance [Ea] to left ventricular end-systolic elastance [Ees]) over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Secondary	Lipopolysaccharide-stimulated monocyte TNF-a secretion	Compare lipopolysaccharide-stimulated monocyte TNF-a secretion over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Secondary	Monocyte adhesion	Compare monocyte adhesion over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Secondary	Plasma renin concentration	Compare plasma renin concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Secondary	Plasma angiopoietin-2 concentration	Compare plasma angiopoietin-2 concentration over time in vasopressin responders vs. non-responders. The active control cohort of patients who are only receiving norepinephrine will serve as a control for this analysis.	Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.