Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis

Phase 3RecruitingNCT06464510

Hospital do Coracao2,800 enrolled

Overview

The norepinephrine and vasopressin for rescue versus early vasopressin for vasopressor dependent sepsis (NoVa) is a phase 3, multicenter, open-label, randomized controlled trial comparing an early vasopressin initiation strategy versus norepinephrine plus vasopressin initiation only as a rescue strategy for hemodynamic management of critically ill patients with vasopressor dependent sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated body response to infection. Its most severe form, septic shock, occurs when underlying circulatory and cellular metabolic abnormalities are pronounced, indicating greater severity and higher mortality. Vasopressor use is a cornerstone aspect in the treatment of critically ill patients with sepsis-associated hemodynamic dysfunction, with norepinephrine, a catecholamine, being the vasopressor of choice. Vasopressin is an endogenous peptide hormone with potential advantages over norepinephrine in a catecholamine-sparing strategy for treating sepsis-associated hemodynamic dysfunction. This is a phase 3, multicenter, open-label, randomized controlled trial. Adult patients with sepsis-associated hemodynamic dysfunction in the ICU may be eligible to participate. We aim to enroll 2,800 patients.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

2,800

Conditions

Septic Shock

Interventions

Early VasopressinDRUG

Early Vasopressin group: Vasopressin up to 0.04U/min initiated after randomization.

Norepinephrine and Vasopressin for RescueDRUG

Norepinephrine and Vasopressin for Rescue group: Vasopressin up to 0.04U/min initiated only if norepinephrine dose exceeds 0.5 μg/kg/min.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with vasopressor dependent sepsis, defined by infection suspicion and antibiotic administration or laboratory confirmed viral infection, plus hypotension with the need of vasopressors for at least one hour; * Admitted or expected to be admitted to the ICU in the next 12 hours * Adequate volume resuscitation in the opinion of the attending physician * Use of norepinephrine \> 0.05μg/Kg/min and ≤ 0.25μg/Kg/min for at least 1 hour and at most 24 hours at the time of inclusion Exclusion Criteria: * Use of norepinephrine \> 0.25μg/Kg/min in the last 24 hours, except when administered transiently in the context of sedation for a procedure or the initial phase of volume resuscitation for a period of less than one hour * Dialysis-dependent chronic kidney disease or acute kidney injury that received renal replacement therapy during current hospitalization or are expected to receive renal replacement therapy in the next 24 hours * Use of other vasopressors (except norepinephrine) at the moment of inclusion * Use of vasopressors for sepsis in the last 7 days * Suspected or confirmed acute mesenteric ischemia * Anaphylaxis or known hypersensitivity to the study drug * Expect to die in the next 24 hours * Medical team not committed to full support at the time of inclusion * Previous inclusion in the study

Locations (8)

Hospital Geral de Caxias do Sul

Caxias do Sul, Rio Grande do Sul, Brazil

RECRUITING

Hospital Nereu Ramos

Florianópolis, Santa Catarina, Brazil

RECRUITING

Hospital SEPACO

São Paulo, S, Brazil

Outcomes

Primary Outcomes

All-cause mortality or renal replacement therapy

Composite of all-cause mortality or renal replacement therapy within 28 days after randomization.

Time frame: 28 days

Secondary Outcomes

All-cause mortality

All-cause mortality within 28 days after randomization

Time frame: 28 days

Renal replacement-therapy

Need of renal replacement therapy within 28 days after randomization.

Time frame: 28 days

Renal replacement-free days

Renal-replacement free days are defined by the number of days a patient is alive and free of renal replacement support between randomization and day 28. Non-survivors will be considered to have zero renal replacement-free days.

Time frame: 28 days

ICU-free days

Number of days a patient is alive and outside the ICU between randomization and day 28. Non-survivors will be considered to have zero ICU-free days.

Time frame: 28 days

Hospital-free days

Number of days a patient is alive and outside the hospital between randomization and day 28. Non-survivors will be considered to have zero hospital-free days.

Time frame: 28 days

Organ support-free days and its components

The definition of organ support involves three components: renal replacement therapy, invasive mechanical ventilation, and vasopressor use. Organ support-free days are defined by the number of days a patient is alive and free of all three organ support therapies between randomization and day 28. Non-survivors will be considered to have zero organ support-free days.

Central Contacts

Bruno M Tomazini, MD

CONTACT

+5511982839173 btomazini@hcor.com.br

Alexandre Biasi Cavalcanti, PhD

CONTACT

+551130536611 abiasi@hcor.com.br

Data from ClinicalTrials.gov

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