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.
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.
Eligibility
Inclusion Criteria:
- Patients with vasopressor dependent sepsis, defined by infection suspicion and antibiotic administration 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