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The study was terminated due to lack of feasibility.
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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:
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 and measurements of oxygen in tissues from a sensor placed on one of the hands will be taken. Participants who are not ordered the drug vasopressin and only ordered the drug norepinephrine will contribute only one blood sample. At the time the sample is collected, advanced echocardiography pictures and measurements of oxygen in tissues from a sensor placed on one of the hands will be taken. This research also involves analyzing data obtained during the participant's hospital stay.
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 and microcirculation measurements. In the current study, the investigators seek to clarify the link between vasopressin, immune response, hemodynamic profile, and microcirculatory measurments. The central goal of this proposal is to identify "vasopressin response" as an easily-identifiable bedside indicator of a distinct septic shock subphenotype.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vasopressin plus norepinephrine | Patients with septic shock ordered vasopressin as an adjunct to norepinephrine |
| |
| Norepinephrine | Active control cohort of patients with septic shock who are only receiving norepinephrine |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vasopressin | Drug | Fixed dosage vasopressin ordered as an adjunctive vasopressor to norepinephrine |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of plasma interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) | Compare baseline ratio of plasma concentrations of interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) 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 45 minutes of order placement). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 45 minutes of order placement). |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma interleukin-1β (IL-1β) concentration | Compare plasma interleukin-1β (IL-1β) 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
Inclusion Criteria:
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Seth Bauer, PharmD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic Main Campus | Cleveland | Ohio | 44195 | United States |
Individual participant data may be available through reasonable request to the study principal investigator and completion of a data use agreement.
Study data will become available at the time of initial manuscript publication and remain available for 5 years after initial manuscript publication.
Individual participant data may be available through reasonable request to the study principal investigator and completion of a data use agreement.
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| D014667 | Vasopressins |
| D001127 | Arginine Vasopressin |
| ID | Term |
|---|---|
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
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Blood collected into EDTA test tubes
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Lipopolysaccharide-stimulated monocyte TNF-α secretion | Compare lipopolysaccharide-stimulated monocyte TNF-α 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| StO2 recovery slope (%/min) | Compare tissue oxygenation (StO2) recovery slope, during the reperfusion phase of a vascular occlusion test (VOT), over time between 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Difference in StO2 (%) | Compare the difference between maximum tissue oxygenation (StO2) and minimum StO2, during the reperfusion phase of a vascular occlusion test (VOT), over time between 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Plasma interferon-gamma (IFN-γ) concentration | Compare plasma interferon-gamma (IFN-γ) 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Plasma vasopressin concentration | Evaluate the association of plasma vasopressin concentration with ratio of plasma interleukin-10 (IL-10) to tumor necrosis factor-α (TNF-α) 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Baseline tissue oxygenation (StO2) | Compare baseline tissue oxygenation (StO2) over time between 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 45 minutes of order placement). |
| Tissue oxygenation (StO2) deperfusion slope | Compare tissue oxygenation (StO2) deperfusion slope, during a vascular occlusion test, over time between 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Minimum tissue oxygenation (StO2) | Compare minimum tissue oxygenation (StO2), during a vascular occlusion test, over time between 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Tissue oxygenation (StO2) area under the curve (AUC) | Compare tissue oxygenation (StO2) area under the curve (AUC), during a vascular occlusion test, over time between 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 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| Capillary refill time (CRT) | Compare capillary refill time (CRT) over time between vasopressin responders vs non-responders. The active control of cohort of patients who are only receiving norepinephrine will serve as a control for this analysis. | Baseline (before vasopressin initiation and within 45 minutes of order placement) through one to six hours after vasopressin initiation. |
| 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 45 minutes of order placement) through the sooner of intensive care unit discharge or 14 days. |
| 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 45 minutes of order placement) through intensive care unit discharge. |
| Incidence of in-hospital mortality | Compare the incidence of hospital mortality in vasopressin responders vs. non-responders. | Baseline (before vasopressin initiation and within 45 minutes of order placement) through hospital discharge. |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |