Clinical trial NCT06426407: Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator
Official title: Vasopressin Hemodynamic Response as a Septic Shock Subphenotype Indicator
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Shock, Septic
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2024-05-23
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with septic shock are eligible for this study. Patients ordered vasopressin as an adjunct to norepinephrine as part of routine care comprise the primary cohort of interest. An active control cohort of patients who are only receiving norepinephrine will also be enrolled.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ratio of plasma interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement).
Secondary outcomes:
measure: Left ventricular ejection fraction (LVEF)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement).
measure: Ratio of ratio of arterial elastance (Ea) to left ventricular end-systolic elastance (Ees)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Lipopolysaccharide-stimulated monocyte TNF-α secretion
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Monocyte adhesion
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma renin concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma angiopoietin-2 concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
Other outcomes:
measure: Plasma interleukin-1β (IL-1β) concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma interleukin-6 (IL-6) concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma interferon-gamma (IFN-γ) concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma C-X-C motif chemokine ligand 10 (CXCL10, also known as interferon gamma-induced protein 10 [IP-10]) concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma granulocyte-colony stimulating factor (G-CSF) concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma E-selectin concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma vasopressin concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Plasma copeptin concentration
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Left ventricular ejection fraction (LVEF) change
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Stroke volume (SV) by echocardiography
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Tricuspid annular plane systolic excursion (TAPSE)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Tricuspid annular systolic plane velocity (TAPSV, also known as RV S')
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Venous-arterial carbon dioxide tension gradient (Pva-CO2)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Central venous oxygen saturation (ScvO2)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Dynamic arterial elastance (Eadyn, the ratio of pulse pressure variation to stroke volume variation)
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through one to six hours after vasopressin initiation.
measure: Clinical trajectory
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through the sooner of intensive care unit discharge or 14 days.
measure: Incidence of in-hospital mortality
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through hospital discharge.
measure: Intensive care unit length of stay
timeFrame: Baseline (before vasopressin initiation and within 30 minutes of order placement) through intensive care unit discharge.
Locations:
Study officials:
affiliation: The Cleveland Clinic
name: Seth Bauer, PharmD
role: PRINCIPAL_INVESTIGATOR
References: