Septic ShockPhase 3NoVaNCT06464510
Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis
A Phase 3 study testing Early Vasopressin and Norepinephrine and Vasopressin for Rescue in people with Septic Shock, run by Hospital do Coracao at 8 sites in Brazil.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Septic Shock
- What is being tested?
- Early Vasopressin and Norepinephrine and Vasopressin for Rescue
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,800 participants
- Where
- 8 sitesBrazil
- Study dates
- 21 Nov 2024to Sep 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Brazil8 sites, 8 recruiting
- Not yet recruiting
Hospital de Amor - Unidade Barretos (Fundação PIO XII)
Barretos, São Paulo
Cristina Amendola
- Recruiting
Hospital Geral de Caxias do Sul
Caxias do Sul, Rio Grande do Sul
Emerson Silva
- Recruiting
Hospital Nereu Ramos
Florianópolis, Santa Catarina
Israel Maia, PhD, israels.maia@gmail.com ;
- Not yet recruiting
Hospital SEPACO
São Paulo, S
Flávio Freitas
- Recruiting
Hospital do Coracao
São Paulo, São Paulo, 05435000
Marcelo Romano, MD
Luzia Taniguchi, MSc
- Not yet recruiting
BP-A Beneficiência Portuguesa de São Paulo
São Paulo, São Paulo
Viviane Veiga, dveiga@uol.com.br
- Not yet recruiting
Hospital Alemão Oswaldo Cruz
São Paulo, São Paulo
Mino Cestari, MD
- Recruiting
Hospital São Paulo - UNIFESP
São Paulo, São Paulo
Flavia Machado, frmachado@unifesp.br;
About this study
Official title: Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis: An Open-label, Multicenter, Randomized, Controlled Trial: NoVa
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.
Read the 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.
- Conditions
- Septic Shock
- Being tested
- Early Vasopressin, Norepinephrine and Vasopressin for Rescue
- Keywords
- Vasopressin, Norepinephrine, Vasopressor dependent sepsis, Septic shock, Critically ill
- Medical subject headings
- Shock, Septic, Diabetes Insipidus, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early VasopressinDrug
Early Vasopressin group: Vasopressin up to 0.04U/min initiated after randomization.
Norepinephrine and Vasopressin for RescueDrug
Norepinephrine and Vasopressin for Rescue group: Vasopressin up to 0.04U/min initiated only if norepinephrine dose exceeds 0.5 μg/kg/min.
| Study group | Role | What they receive |
|---|---|---|
| Early Vasopressin | Experimental | 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. Receives: Drug: Early Vasopressin |
| Norepinephrine plus vasopressin for rescue | Active comparator | 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. Receives: Drug: Norepinephrine and Vasopressin for Rescue |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause mortality or renal replacement therapy
Composite of all-cause mortality or renal replacement therapy within 28 days after randomization.
Measured: 28 days
Secondary outcomes (8)
All-cause mortality
All-cause mortality within 28 days after randomization
Measured: 28 days
Renal replacement-therapy
Need of renal replacement therapy within 28 days after randomization.
Measured: 28 days
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.
Measured: 28 days
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.
Measured: 28 days
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.
Measured: 28 days
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.
Measured: 28 days
Cardiac arrhythmias
Occurrence of cardiac arrhythmias between randomization and day 28
Measured: 28 days
Ischemic events
Occurrence of mesenteric ischemia, ischemic stroke, digital ischemia and acute coronary syndrome between randomization and day 28
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2024
- Study start21 Nov 2024
- Primary completionAug 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Septic ShockStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital do Coracao
- Sponsor type
- University, hospital or other
- Collaborators
- Brazilian Research In Intensive Care Network, National Institute of Science and Technology (INCT) in Precision Intensive Care Medicine
- Responsible party
- Sponsor
- Investigators
- Bruno M Tomazini, MD, Principal investigator, Hcor Research InstituteMachado R Flavia, PhD, Study chair, Universidade Federal de São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06464510
- Sponsor's protocol ID
- ip_hcor_nova
- Acronym
- NoVa
- Status last verified
- Mar 2025
- First submitted
- 11 Jun 2024
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Submission of a statistical analysis plan for the purposed analyses for the Steering Committee evaluation. Compliance with Brazilian data privacy law.
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Norepinephrine and Vasopressin for Rescue Versus Early Vasopressin for Vasopressor Dependent Sepsis: An Open-label, Multicenter, Randomized, Controlled Trial: NoVa
- ClinicalTrials.gov ID
- NCT06464510
- Acronym / sponsor ID
- NoVa / ip_hcor_nova
- Conditions
- Septic Shock
- Keywords
- Vasopressin, Norepinephrine, Vasopressor dependent sepsis, Septic shock, Critically ill
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2,800 participants (estimated)
- Lead sponsor
- Hospital do CoracaoUniversity, hospital or other
- Collaborators
- Brazilian Research In Intensive Care Network, National Institute of Science and Technology (INCT) in Precision Intensive Care Medicine
- Study start
- 21 Nov 2024 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 18 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Vasopressin | Experimental | Drug: Early VasopressinAfter 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 | Active comparator | Drug: Norepinephrine and Vasopressin for RescueAfter 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early VasopressinEarly Vasopressin group: Vasopressin up to 0.04U/min initiated after randomization. | Drug | Early Vasopressin |
| Norepinephrine and Vasopressin for RescueNorepinephrine and Vasopressin for Rescue group: Vasopressin up to 0.04U/min initiated only if norepinephrine dose exceeds 0.5 μg/kg/min. | Drug | Norepinephrine plus vasopressin for rescue |
Primary outcome
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.
8 secondary outcomes
All-cause mortality
Time frame: 28 days
Renal replacement-therapy
Time frame: 28 days
Renal replacement-free days
Time frame: 28 days
ICU-free days
Time frame: 28 days
Hospital-free days
Time frame: 28 days
Organ support-free days and its components
Time frame: 28 days
Cardiac arrhythmias
Time frame: 28 days
Ischemic events
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Individual participant dataSharing planned: Yes. Submission of a statistical analysis plan for the purposed analyses for the Steering Committee evaluation. Compliance with Brazilian data privacy law.
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Sepsis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Bruno M Tomazini, MD principal investigator
Hcor Research Institute
Machado R Flavia, PhD study chair
Universidade Federal de São Paulo
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Early Vasopressin and Norepinephrine and Vasopressin for Rescue in people with Septic Shock, run by Hospital do Coracao at 8 sites in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Bruno M Tomazini, MD (+5511982839173, btomazini@hcor.com.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause mortality or renal replacement therapy (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2026.