Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis

Septic Shock Clinical Trial

— NoVa  

Official title:

Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis: An Open-label, Multicenter, Randomized, Controlled Trial: NoVa

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06464510
• Other study ID #: ip_hcor_nova
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 2024
• Est. completion date: September 2027

Study information

• Verified date: June 2024
• Source: Hospital do Coracao
• Contact: Bruno M Tomazini, MD
• Phone: +5511982839173
• Email: btomazini[@]hcor.com.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 2800
• Est. completion date: September 2027
• Est. primary completion date: August 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

• 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

Related Conditions & MeSH terms

• Sepsis
• Septic Shock
• Shock, Septic

Intervention

Drug:
• Early Vasopressin
Early Vasopressin group: Vasopressin up to 0.04U/min initiated after randomization.
• Norepinephrine 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.

Locations

Country	Name	City	State
Brazil	Hospital de Amor - Unidade Barretos (Fundação PIO XII)	Barretos	SP
Brazil	Hospital Geral de Caxias do Sul	Caxias do Sul	RS
Brazil	Hospital Nereu Ramos	Florianópolis	Sc
Brazil	BP-A Beneficiência Portuguesa de São Paulo	São Paulo
Brazil	Hospital Alemão Oswaldo Cruz	São Paulo	SP
Brazil	Hospital do Coracao	São Paulo
Brazil	Hospital São Paulo - UNIFESP	São Paulo	SP
Brazil	Hospital SEPACO	São Paulo	S
Brazil	Hospital Sírio-Libanês	São Paulo	SP

Sponsors (2)

Lead Sponsor	Collaborator
Hospital do Coracao	Brazilian Research in Intensive Care Network (BRICNet)

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause mortality or renal replacement therapy	Composite of all-cause mortality or renal replacement therapy within 28 days after randomization.	28 days
Secondary	All-cause mortality	All-cause mortality within 28 days after randomization	28 days
Secondary	Renal replacement-therapy	Need of renal replacement therapy within 28 days after randomization.	28 days
Secondary	Renal replacement-free 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.	28 days
Secondary	ICU-free 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.	28 days
Secondary	Hospital-free 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.	28 days
Secondary	Organ support-free days and its components	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.	28 days
Secondary	Cardiac arrhythmias	Occurrence of cardiac arrhythmias between randomization and day 28	28 days
Secondary	Ischemic events	Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28	28 days