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

Official title

Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis: An Open-label, Multicenter, Randomized, Controlled Trial: NoVa

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• All-cause mortality or renal replacement therapy [Time frame: 28 days]

Secondary outcome measures (8)

• All-cause mortality [Time frame: 28 days]
• Renal replacement-therapy [Time frame: 28 days]
• Renal replacement-free days [Time frame: 28 days]
• ICU-free days [Time frame: 28 days]
• Hospital-free days [Time frame: 28 days]
• Organ support-free days and its components [Time frame: 28 days]
• Cardiac arrhythmias [Time frame: 28 days]
• Ischemic events [Time frame: 28 days]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 8 centers

• Hospital Geral de Caxias do Sul — Caxias do Sul
• Hospital Nereu Ramos — Florianópolis
• Hospital SEPACO — São Paulo
• Hospital de Amor - Unidade Barretos (Fundação PIO XII) — Barretos
• Hospital do Coracao — São Paulo
• BP-A Beneficiência Portuguesa de São Paulo — São Paulo
• Hospital Alemão Oswaldo Cruz — São Paulo
• Hospital São Paulo - UNIFESP — São Paulo

Identifiers

NCT: NCT06464510 · ip_hcor_nova

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗