Renal Outcomes in the Early Use of Vasopressin in the Treatment of Septic Shock (EVSS)

The aim of the present study is to verify whether the earlier association of vasopressin and norepinephrine, in patients in septic shock, determines variations in terms of use of renal function replacement techniques in the first 7 days of hospitalization in Intensive Care, compared to patients in whom vasopressin is added only when norepinephrine reaches a higher dose.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Renal Function Replacement
• Intervention / Treatment: Drug: vasopressin infusion when the norepinephrine dosage is equal to or greater than 0.25 mcg/kg/min; Drug: vasopressin infusion when the norepinephrine dosage is equal to or greater than 0.5 mcg/kg/min

Detailed Description

The aim of the present study is to verify whether the earlier association of vasopressin and norepinephrine, in patients in septic shock, determines variations in terms of use of renal function replacement techniques in the first 7 days of hospitalization in Intensive Care, compared to patients in whom vasopressin is added only when norepinephrine reaches a higher dose. The study is aimed at patients admitted to the ICU with a diagnosis of septic shock on admission or in the first 24 hours of admission.

Patients will be divided and randomized in a 1:1 ratio through a computer-generated scheme, when the dose of norepinephrine administered is ≥ 0.25 mcg/kg/min, into the following groups:

• Group A: when the norepinephrine dosage is equal to or greater than 0.25 mcg/kg/min in the absence of adequate MAP (Mean arterial pressure >65 mmhg), vasopressin infusion will be associated with the standard dosage of 0.3UI/min.
• Group B (control): the infusion of vasopressin at a dosage of 0.3 IU/min will be associated if norepinephrine exceeds the dosage of 0.5 mcg/kg/min in the absence of adequate MAP.

• Study Type: Interventional
• Enrollment (Estimated): 264
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lorenzo Giuntoli, Md; Phone Number: 0516478868; Email: lorenzo.giuntoli@ausl.bologna.it

Study Locations

• Italy
  • Bologna, Italy, 40100
    • Recruiting
    • Azienda Unità Sanitaria Locale
    • Contact: Lorenzo Giuntoli, Md; Phone Number: 0516478868; Email: lorenzo.giuntoli@ausl.bologna.it
    • Principal Investigator: Lorenzo Giuntoli, Md

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• patients suffering from septic shock hospitalized in an intensive setting
• patients over 18 years and under 80 years of age
• patients within 24 hours of clinical diagnosis, and requiring, in this time window, a norepinephrine dosage equal to or greater than 0.25 mcg/kg/min according to the patient's ideal weight (IBW)
• patients capable of expressing informed consent to treatment.

Exclusion Criteria:

• patients in the absence of consent to participate in the study and to the processing of personal and particular data;
• patients under 18 years of age or over 80 years of age;
• patients who died within the first 24 hours of admission to the ICU;
• patients requiring a norepinephrine dosage lower than 0.25 mcg/kg/min in the first 24 hours of hospitalization in the ICU;
• patients with recent acute coronary syndrome (within the previous 7 days);
• patients with allergy/intolerance to the drugs used in the study or to any component of the study drug including excipients;
• pregnant patients;
• breastfeeding individuals;
• patients who need to start renal replacement treatment within 24 hours of admission to the ICU for dialysis emergencies that cannot be deferred;
• patients with a history of end-stage renal failure or already undergoing dialysis treatment (CKD stages 4 and 5, with glomerular filtration < 30 ml/min);
• single kidney patients;
• patients with bilateral renal hypoplasia;
• patients undergoing kidney transplant;
• patients undergoing haemoperfusion with an adsorbent cartridge for bacterial endotoxin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Group A: when the norepinephrine dosage is equal to or greater than 0.25 mcg/kg/min in the absence of adequate MAP (Mean arterial pressure >65 mmhg), vasopressin infusion will be associated with the standard dosage of 0.3UI/min.	Drug: vasopressin infusion when the norepinephrine dosage is equal to or greater than 0.25 mcg/kg/min; when the norepinephrine dosage is equal to or greater than 0.25 mcg/kg/min in the absence of adequate MAP (Mean arterial pressure >65 mmhg), vasopressin infusion will be associated with the standard dosage of 0.3UI/min.
Active Comparator: Group B; Group B (control): the infusion of vasopressin at a dosage of 0.3 IU/min will be associated if norepinephrine exceeds the dosage of 0.5 mcg/kg/min in the absence of adequate MAP.	Drug: vasopressin infusion when the norepinephrine dosage is equal to or greater than 0.5 mcg/kg/min; the infusion of vasopressin at a dosage of 0.3 IU/min will be associated if norepinephrine exceeds the dosage of 0.5 mcg/kg/min in the absence of adequate MAP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30% or more reduction in terms of the use of renal function replacement	The primary objective of the study is to verify whether the earlier association of vasopressin and norepinephrine determines a 30% or more reduction in terms of the use of renal function replacement techniques in the first 7 days of hospitalization in the Intensive Care Unit (ICU), compared to patients in whom the vasopressin is added only when norepinephrine reaches a higher dosage.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
early association of vasopressin improves renal function	To assess the protective effect of early vasopressin association, the Kidigo score will be calculated for every subject at enrollment time, and daily, for 7 days. The maximum value and the greatest increase will be evaluated and compared between study and control group	7 days
rly addition of vasopressin modifies renal perfusion	verify whether the early addition of vasopressin modifies renal perfusion assessed ultrasoundally according to the CEUS method;	7 days
addition of vasopressin modifies the fluid balance of patients	To assess the impact of early vasopressin association on the total amount of fluids administrated in the resuscitative phase of septic shock treatment, the fluid balance at 48 hours and 72 hours since ICU admission will be calculated for every subject, and compared between study and control group.	48 and 72 hours
early combined treatment with vasopressin reduces the duration of the need for CRRT	verify whether early combined treatment with vasopressin reduces the duration of the need for CRRT (Continuous Renal Replacement Therapy) in patients who require such support during hospitalization in the ICU	7 days
early association of vasopressin reduces the onset of supraventricular arrhythmias	verify whether the early association of vasopressin reduces the onset of supraventricular arrhythmias (atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia) during treatment with vasopressor drugs	7 days
intestinal and/or digital and/or limb ischemia;	The incidence of intestinal and/or digital and/or limb ischemia during the study period (7 days since enrollment) will be evaluated and compared between study and control group.	7 days since enrollment
Length of stay in ICU	Length of stay in ICU (days) will be compared between study and control group	28 and 90 days
Mortality	Mortality at 28 and 90 days will be evaluated for every subject and between study and control group	28 and 90 days

Collaborators and Investigators

• Sponsor: Azienda Usl di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): May 15, 2024
• Primary Completion (Estimated): May 15, 2026
• Study Completion (Estimated): May 15, 2026

Study Registration Dates

• First Submitted: May 14, 2024
• First Submitted That Met QC Criteria: June 17, 2024
• First Posted (Actual): June 24, 2024

Study Record Updates

• Last Update Posted (Actual): June 24, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Septic Shock; norepinephrine; vasopressin; renal function replacement
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Natriuretic Agents; Hemostatics; Coagulants; Sympathomimetics; Vasoconstrictor Agents; Antidiuretic Agents; Norepinephrine; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: 23171 - EVSS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No