Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis
- Conditions
- Septic Shock
- Interventions
- Registration Number
- NCT06464510
- Lead Sponsor
- Hospital do Coracao
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2800
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Early Vasopressin Early Vasopressin After randomization, vasopressin will be initiated and titrated up to 0.04U/min to maintain the target mean arterial pressure (MAP). Concurrently, norepinephrine will be reduced, with the goal of using the maximum dose of vasopressin and minimizing or eliminating the use of norepinephrine, while still maintaining the target MAP. Norepinephrine plus vasopressin for rescue Norepinephrine and Vasopressin for Rescue After randomization, norepinephrine will be titrated to maintain the target MAP. Vasopressin will be introduced as a rescue strategy only if the norepinephrine dose exceeds 0.5 μg/kg/min. Once vasopressin is initiated, it can be titrated up to 0.04U/min to help maintain the target MAP if the norepinephrine dose remains above 0.5 μg/kg/min.
- Primary Outcome Measures
Name Time Method All-cause mortality or renal replacement therapy 28 days Composite of all-cause mortality or renal replacement therapy within 28 days after randomization.
- Secondary Outcome Measures
Name Time Method All-cause mortality 28 days All-cause mortality within 28 days after randomization
Renal replacement-therapy 28 days Need of renal replacement therapy within 28 days after randomization.
Ischemic events 28 days Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28
Renal replacement-free days 28 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.
ICU-free days 28 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.
Hospital-free days 28 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.
Organ support-free days and its components 28 days 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.Cardiac arrhythmias 28 days Occurrence of cardiac arrhythmias between randomization and day 28
Trial Locations
- Locations (8)
Hospital Geral de Caxias do Sul
🇧🇷Caxias do Sul, RS, Brazil
Hospital Nereu Ramos
🇧🇷Florianópolis, Sc, Brazil
Hospital de Amor - Unidade Barretos (Fundação PIO XII)
🇧🇷Barretos, SP, Brazil
Hospital Alemão Oswaldo Cruz
🇧🇷São Paulo, SP, Brazil
Hospital São Paulo - UNIFESP
🇧🇷São Paulo, SP, Brazil
Hospital SEPACO
🇧🇷São Paulo, S, Brazil
Hospital do Coracao
🇧🇷São Paulo, Brazil
BP-A Beneficiência Portuguesa de São Paulo
🇧🇷São Paulo, Brazil