Septic Shock
Conditions
Keywords
Vasopressin, Norepinephrine, Vasopressor dependent sepsis, Septic shock, Critically ill
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.
Interventions
DRUGEarly Vasopressin
Early Vasopressin group: Vasopressin up to 0.04U/min initiated after randomization.
DRUGNorepinephrine 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.
Sponsors
Hospital do Coracao
Brazilian Research in Intensive Care Network (BRICNet)
National Institute of Science and Technology (INCT) in Precision Intensive Care Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality or renal replacement therapy | 28 days | Composite of all-cause mortality or renal replacement therapy within 28 days after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| Ischemic events | 28 days | Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28 |
Countries
Brazil
Contacts
CONTACTBruno M Tomazini, MD
CONTACTAlexandre Biasi Cavalcanti, PhD
PRINCIPAL_INVESTIGATORBruno M Tomazini, MD
Hcor Research Institute
STUDY_CHAIRMachado R Flavia, PhD
Universidade Federal de São Paulo
Outcome results
None listed