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Vasoplegic Syndrome of Cardiac SurgeryPhase 4INVASCNCT06934798

Inotropic Effects of Vasopressin Versus Noradrenaline In Patients With Vasoplegic Syndrome After Cardiac Surgery

A Phase 4 study testing Vasopressin intravenous infusion and Norepinephrine intravenous infusion in people with Vasoplegic Syndrome of Cardiac Surgery, run by University of Sao Paulo at 1 site in Brazil.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This is a randomized, double-blind clinical trial designed to compare the inotropic effects of vasopressin versus norepinephrine in patients who develop vasoplegic syndrome in the immediate postoperative period following cardiac surgery. Read more about this study

Who is it for?
Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for
Vasoplegic Syndrome of Cardiac Surgery
What is being tested?
Vasopressin intravenous infusion and Norepinephrine intravenous infusion
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
350 participants
Where
1 siteBrazil
Study dates
1 Apr 2024to 30 Jul 2025
Phase
Phase 4
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
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age over 18.
  • Patients undergoing coronary artery bypass grafting, valve surgery or both, with a diagnosis of vasoplegic syndrome in the immediate postoperative period (<24 hours), defined as mean arterial pressure < 65 mmHg (measured using an invasive blood pressure catheter) and resistance to fluid replacement - at least 1000ml of crystalloids.

Who cannot join

  • Pregnancy or breastfeeding.
  • Aortic surgery.
  • Surgeries to correct congenital heart disease.
  • Heart transplants.
  • Emergency surgery.
  • Use of vasopressor therapy in the preoperative period.
Show all 12Show fewer
  • Presence of a ventricular assist device other than an intra-aortic balloon in the postoperative period.
  • Severe hyponatremia in the postoperative period (serum sodium less than 130mEq/l).
  • Postoperative acute coronary syndrome.
  • Mesenteric ischemia in the postoperative period.
  • History of Raynaud's disease.
  • History of neoplasia.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

José León contact

+55 (11) 2661-5795

aro@incor.usp.br

Brazil1 site, 1 recruiting

  • Instituto do Coração HCFMUSP

    São Paulo, 05403-000

    José D León, Dr, +55 (11) 2661-5795, aro@incor.usp.br

    Ludhmila A Hajjar, Full Professor

    Recruiting

Other trials in Brazil

About this study

This is a randomized, double-blind clinical trial designed to compare the inotropic effects of vasopressin versus norepinephrine in patients who develop vasoplegic syndrome in the immediate postoperative period following cardiac surgery.

Vasoplegic syndrome is characterized by severe hypotension due to systemic vasodilation, despite adequate fluid resuscitation and preserved or elevated cardiac output. Vasopressors are essential in restoring hemodynamic stability in this context; however, their impact on myocardial performance remains uncertain. While norepinephrine is the standard first-line agent, vasopressin has shown potential benefits, including reduced catecholamine exposure and fewer adverse cardiovascular effects.

This study aims to assess changes in cardiac output and other echocardiographic and hemodynamic parameters after administration of either vasopressin or norepinephrine. The findings are expected to contribute to optimizing vasopressor selection in vasoplegic patients after cardiac surgery and improving clinical outcomes.

Read the detailed description

This prospective, randomized, double-blind clinical trial investigates the inotropic effects of vasopressin versus norepinephrine in patients who develop vasoplegic syndrome (VS) in the immediate postoperative period following cardiac surgery.

Vasoplegic syndrome is characterized by severe hypotension with low systemic vascular resistance despite adequate cardiac output, often unresponsive to standard fluid resuscitation and catecholamine vasopressors. It is associated with significant morbidity and mortality, especially in cardiac surgery patients. In recent years, vasopressin has been explored as an alternative or adjunctive treatment due to its different mechanism of action and potentially fewer adverse effects compared to catecholamines.

Eligible patients (≥18 years) undergoing coronary artery bypass grafting or valve surgery, who develop vasoplegic syndrome within 24 hours postoperatively, will be randomized in a 1:1 ratio to receive vasopressin or norepinephrine. Drug allocation will be blinded to the clinical and research teams, with identically prepared infusion bags.

The study protocol includes a detailed vasopressor infusion regimen, beginning at 5 mL/h with titration every 10 minutes to a maximum of 30 mL/h, aiming for a target mean arterial pressure (MAP) ≥65 mmHg. Hemodynamic parameters (SBP, DBP, MAP, HR, lactate, SVO₂, CO₂ gap) and echocardiographic indices (LVEF, TAPSE, VTI, CO, SVR) will be collected at baseline (T0) and upon reaching the MAP goal (T1).

Primary endpoint: Comparative assessment of the inotropic effects between the two vasopressors based on echocardiographic and hemodynamic changes from T0 to T1.

Sample size: 175 patients per arm, considering a 30% effect size and 5% attrition rate, powered at 80% with a 5% type I error.

Statistical analysis will follow an intention-to-treat approach using appropriate parametric and non-parametric tests, with p-values <0.05 considered statistically significant.

This trial is expected to provide clinically relevant data on the efficacy and safety of vasopressin in improving myocardial performance in vasoplegic patients, potentially supporting its use as a first-line vasopressor in this context

Being tested
Vasopressin intravenous infusion, Norepinephrine intravenous infusion
Keywords
Shock Cardiogenic, Postoperative Complications, Cardiac Surgical Procedures
Medical subject headings
Shock, Cardiogenic, Postoperative Complications

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vasopressin intravenous infusionDrug

    Also called Arginine Vasopressin, ADH, Pitressin

    Vasopressin will be administered intravenously in a blinded 250 mL bag of 5% glucose solution, at a final concentration of 0.12 U/mL. The infusion will begin at 5 mL/h and be increased by 2.5 mL/h every 10 minutes during the first hour, up to a maximum rate of 30 mL/h (equivalent to doses from 0.01 to 0.06 U/min). The target is to reach and maintain mean arterial pressure (MAP) ≥65 mmHg. If this is not achieved, open-label norepinephrine may be added. Hemodynamic and echocardiographic parameters will be measured before and after the target MAP is reached.

  • Norepinephrine intravenous infusionDrug

    Also called Noradrenaline, Levophed

    Norepinephrine will be administered intravenously in a blinded 250 mL bag of 5% glucose solution, at a final concentration of 120 µg/mL. The infusion will begin at 5 mL/h and be increased by 2.5 mL/h every 10 minutes during the first hour, up to a maximum rate of 30 mL/h (equivalent to doses from 10 to 60 µg/min). The goal is to reach and maintain MAP ≥65 mmHg. If the MAP target is not reached, open-label norepinephrine may be initiated. Clinical and hemodynamic parameters will be collected at baseline and after MAP stabilization.

Study groups in NCT06934798
Study groupRoleWhat they receive
VasopressinExperimentalParticipants randomized to this arm will receive vasopressin intravenously in a blinded solution prepared by the pharmacy (final concentration: 0.12 U/mL in 250 mL of 5% glucose solution). The infusion will start at 5 mL/h and will be titrated by 2.5 mL/h every 10 minutes up to a maximum of 30 mL/h, corresponding to doses between 0.01 and 0.06 U/min. The infusion will be maintained until the target mean arterial pressure (MAP) ≥65 mmHg is achieved. If this target is not reached, open-label norepinephrine may be initiated. Hemodynamic and laboratory parameters will be collected at the start (T0) and after achieving target pressure (T1).
Receives: Drug: Vasopressin intravenous infusion
NoradrenalineActive comparatorParticipants randomized to this arm will receive norepinephrine intravenously in a blinded solution prepared by the pharmacy (final concentration: 120 µg/mL in 250 mL of 5% glucose solution). The infusion will start at 5 mL/h and will be titrated by 2.5 mL/h every 10 minutes up to a maximum of 30 mL/h, corresponding to doses between 10 and 60 µg/min. The infusion will be maintained until the target mean arterial pressure (MAP) ≥65 mmHg is achieved. If this target is not reached, additional open-label norepinephrine may be started. Hemodynamic and laboratory parameters will be collected at the start (T0) and after achieving target pressure (T1).
Receives: Drug: Norepinephrine intravenous infusion

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in inotropic function assessed by cardiac output between T0 and T1

    The primary outcome is the variation in cardiac output (CO), measured by transthoracic echocardiography, from the beginning of the vasopressor infusion (T0) until the achievement of target mean arterial pressure ≥65 mmHg (T1), in patients with vasoplegic syndrome after cardiac surgery. This measurement reflects the inotropic effect of vasopressin versus norepinephrine

    Measured: Up to 1 hour after initiation of vasopressor therapy

Secondary outcomes (7)

  1. Change in left ventricular ejection fraction (LVEF) between T0 and T1

    LVEF will be measured using transthoracic echocardiography at T0 (baseline) and T1 (after achieving MAP ≥65 mmHg), to assess changes in left ventricular systolic function.

    Measured: Up to 1 hour after vasopressor initiation

  2. Time to achieve target mean arterial pressure (MAP ≥65 mmHg)

    Time (in minutes) between the start of vasopressor infusion (T0) and the point at which MAP ≥65 mmHg is reached (T1), indicating hemodynamic stabilization.

    Measured: Up to 1 hour

  3. Change in heart rate (HR) between T0 and T1

    Heart rate will be measured at baseline (T0) and after stabilization (T1) to assess the chronotropic effect of each drug.

    Measured: Up to 1 hour

  4. Change in arterial lactate levels between T0 and T1

    Arterial lactate will be used as a marker of tissue perfusion, measured at T0 and T1, to evaluate response to vasopressor therapy.

    Measured: Up to 1 hour

  5. Change in central venous oxygen saturation (SvO₂)

    SvO₂ will be measured at T0 and T1 as an indirect marker of oxygen delivery and cardiac output adequacy.

    Measured: Up to 1 hour

  6. Change in CO₂ gap (central venous-to-arterial CO₂ difference)

    The CO₂ gap will be evaluated at T0 and T1 to assess tissue hypoperfusion and response to vasopressor use.

    Measured: Up to 1 hour

  7. Need for additional open-label norepinephrine

    Number of participants in each arm requiring additional norepinephrine outside the study drug to reach MAP ≥65 mmHg.

    Measured: During initial vasopressor titration (up to 1 hour)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2025
  2. Study start1 Apr 2024
  3. Primary completion30 Jul 2025 (estimated)
  4. Study completion30 Jul 2025 (estimated)

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
350 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06934798
Sponsor's protocol ID
16286719.1.0000.8069
Acronym
INVASC
Status last verified
Apr 2025
First submitted
11 Apr 2025
Last updated
30 Apr 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Belletti A, Musu M, Silvetti S, Saleh O, Pasin L, Monaco F, Hajjar LA, Fominskiy E, Finco G, Zangrillo A, Landoni G. Non-Adrenergic Vasopressors in Patients with or at Risk for Vasodilatory Shock. A Systematic Review and Meta-Analysis of Randomized Trials. PLoS One. 2015 Nov 11;10(11):e0142605. doi: 10.1371/journal.pone.0142605. eCollection 2015.

    PubMed 26558621

  • Pelletier JS, Dicken B, Bigam D, Cheung PY. Cardiac effects of vasopressin. J Cardiovasc Pharmacol. 2014 Jul;64(1):100-7. doi: 10.1097/FJC.0000000000000092.

    PubMed 24621650

  • Dunser MW, Mayr AJ, Ulmer H, Knotzer H, Sumann G, Pajk W, Friesenecker B, Hasibeder WR. Arginine vasopressin in advanced vasodilatory shock: a prospective, randomized, controlled study. Circulation. 2003 May 13;107(18):2313-9. doi: 10.1161/01.CIR.0000066692.71008.BB. Epub 2003 May 5.

    PubMed 12732600

  • Hamzaoui O, Jozwiak M, Geffriaud T, Sztrymf B, Prat D, Jacobs F, Monnet X, Trouiller P, Richard C, Teboul JL. Norepinephrine exerts an inotropic effect during the early phase of human septic shock. Br J Anaesth. 2018 Mar;120(3):517-524. doi: 10.1016/j.bja.2017.11.065. Epub 2017 Nov 21.

    PubMed 29452808

  • Hamzaoui O, Georger JF, Monnet X, Ksouri H, Maizel J, Richard C, Teboul JL. Early administration of norepinephrine increases cardiac preload and cardiac output in septic patients with life-threatening hypotension. Crit Care. 2010;14(4):R142. doi: 10.1186/cc9207. Epub 2010 Jul 29.

    PubMed 20670424

  • Elgebaly AS, Sabry M. Infusion of low-dose vasopressin improves left ventricular function during separation from cardiopulmonary bypass: a double-blind randomized study. Ann Card Anaesth. 2012 Apr-Jun;15(2):128-33. doi: 10.4103/0971-9784.95076.

    PubMed 22508204

  • Gordon AC, Mason AJ, Perkins GD, Ashby D, Brett SJ. Protocol for a randomised controlled trial of VAsopressin versus Noradrenaline as Initial therapy in Septic sHock (VANISH). BMJ Open. 2014 Jul 3;4(7):e005866. doi: 10.1136/bmjopen-2014-005866.

    PubMed 24993769

  • Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D; VASST Investigators. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008 Feb 28;358(9):877-87. doi: 10.1056/NEJMoa067373.

    PubMed 18305265

  • Morales DL, Garrido MJ, Madigan JD, Helman DN, Faber J, Williams MR, Landry DW, Oz MC. A double-blind randomized trial: prophylactic vasopressin reduces hypotension after cardiopulmonary bypass. Ann Thorac Surg. 2003 Mar;75(3):926-30. doi: 10.1016/s0003-4975(02)04408-9.

    PubMed 12645718

  • McIntyre WF, Um KJ, Alhazzani W, Lengyel AP, Hajjar L, Gordon AC, Lamontagne F, Healey JS, Whitlock RP, Belley-Cote EP. Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis. JAMA. 2018 May 8;319(18):1889-1900. doi: 10.1001/jama.2018.4528.

    PubMed 29801010

  • Masarwa R, Paret G, Perlman A, Reif S, Raccah BH, Matok I. Role of vasopressin and terlipressin in refractory shock compared to conventional therapy in the neonatal and pediatric population: a systematic review, meta-analysis, and trial sequential analysis. Crit Care. 2017 Jan 5;21(1):1. doi: 10.1186/s13054-016-1589-6.

    PubMed 28057037

  • Asfar P, Chawla L, Lerolle N, Radermacher P. Angiotensin-II: more than just another vasoconstrictor to treat septic shock-induced hypotension?*. Crit Care Med. 2014 Aug;42(8):1961-3. doi: 10.1097/CCM.0000000000000436. No abstract available.

    PubMed 25029144

  • Hajjar LA, Vincent JL, Barbosa Gomes Galas FR, Rhodes A, Landoni G, Osawa EA, Melo RR, Sundin MR, Grande SM, Gaiotto FA, Pomerantzeff PM, Dallan LO, Franco RA, Nakamura RE, Lisboa LA, de Almeida JP, Gerent AM, Souza DH, Gaiane MA, Fukushima JT, Park CL, Zambolim C, Rocha Ferreira GS, Strabelli TM, Fernandes FL, Camara L, Zeferino S, Santos VG, Piccioni MA, Jatene FB, Costa Auler JO Jr, Filho RK. Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial. Anesthesiology. 2017 Jan;126(1):85-93. doi: 10.1097/ALN.0000000000001434.

    PubMed 27841822

  • Hartmann C, Radermacher P, Wepler M, Nussbaum B. Non-Hemodynamic Effects of Catecholamines. Shock. 2017 Oct;48(4):390-400. doi: 10.1097/SHK.0000000000000879.

    PubMed 28915214

  • Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F. Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med. 2008 Jun;36(6):1701-6. doi: 10.1097/CCM.0b013e318174db05.

    PubMed 18496368

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Vasopressin intravenous infusion and Norepinephrine intravenous infusion in people with Vasoplegic Syndrome of Cardiac Surgery, run by University of Sao Paulo at 1 site 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 2 inclusion and 12 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 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 José León (+55 (11) 2661-5795, aro@incor.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in inotropic function assessed by cardiac output between T0 and T1 (time frame: Up to 1 hour after initiation of vasopressor therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06934798, which also lists 21 linked publications.

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 Apr 2025; AzTrials last refreshed its copy on 8 Nov 2026.

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