Clinical trial NCT06464510: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Septic Shock
Keywords: Vasopressin
Norepinephrine
Vasopressor dependent sepsis
Septic shock
Critically ill
Lead sponsor: Hospital do Coracao
Sponsor class: OTHER
Collaborators: name: Brazilian Research in Intensive Care Network (BRICNet)
First posted: 2024-06-18
Enrollment: 2800
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality or renal replacement therapy
timeFrame: 28 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: 28 days
measure: Renal replacement-therapy
timeFrame: 28 days
measure: Renal replacement-free days
timeFrame: 28 days
measure: ICU-free days
timeFrame: 28 days
measure: Hospital-free days
timeFrame: 28 days
measure: Organ support-free days and its components
timeFrame: 28 days
measure: Cardiac arrhythmias
timeFrame: 28 days
measure: Ischemic events
timeFrame: 28 days
Other outcomes:
Locations:
city: Caxias do Sul
country: Brazil
facility: Hospital Geral de Caxias do Sul
state: RS
city: Florianópolis
country: Brazil
facility: Hospital Nereu Ramos
state: Sc
city: Barretos
country: Brazil
facility: Hospital de Amor - Unidade Barretos (Fundação PIO XII)
state: SP
city: São Paulo
country: Brazil
facility: Hospital Alemão Oswaldo Cruz
state: SP
city: São Paulo
country: Brazil
facility: Hospital São Paulo - UNIFESP
state: SP
city: São Paulo
country: Brazil
facility: Hospital SEPACO
state: S
city: São Paulo
country: Brazil
facility: Hospital do Coracao
city: São Paulo
country: Brazil
facility: BP-A Beneficiência Portuguesa de São Paulo
Study officials:
affiliation: Hcor Research Institute
name: Bruno M Tomazini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Federal de São Paulo
name: Machado R Flavia, PhD
role: STUDY_CHAIR
References: