Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis: An Open-label, Multicenter, Randomized, Controlled Trial: NoVa
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Hospital do Coracao
- Enrollment
- 2,800
- Locations
- 8
- Primary Endpoint
- All-cause mortality or renal replacement therapy
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Early Vasopressin (Drug)
Norepinephrine plus 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.
Intervention: Norepinephrine and Vasopressin for Rescue (Drug)
Outcomes
Primary Outcomes
All-cause mortality or renal replacement therapy
Time Frame: 28 days
Composite of all-cause mortality or renal replacement therapy within 28 days after randomization.
Secondary Outcomes
- All-cause mortality(28 days)
- Renal replacement-therapy(28 days)
- Ischemic events(28 days)
- Renal replacement-free days(28 days)
- ICU-free days(28 days)
- Hospital-free days(28 days)
- Organ support-free days and its components(28 days)
- Cardiac arrhythmias(28 days)