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

NCT06934798 | Recruiting Phase 4

• 1 other identifier: 16286719.1.0000.8069
• Study Type: interventional
• Target: 350
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Vasoplegic Syndrome of Cardiac Surgery

Keywords

Shock Cardiogenic; Postoperative Complications; Cardiac Surgical Procedures

Outcome Measures

Primary Outcomes (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

  Up to 1 hour after initiation of vasopressor therapy

Secondary Outcomes (7)

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

  Up to 1 hour after vasopressor initiation

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

  Up to 1 hour

• Change in heart rate (HR) between T0 and T1

  Up to 1 hour

• Change in arterial lactate levels between T0 and T1

  Up to 1 hour

• Change in central venous oxygen saturation (SvO₂)

  Up to 1 hour

Study Arms (2)

Vasopressin

EXPERIMENTAL

Participants 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).

Drug: Vasopressin intravenous infusion

Noradrenaline

ACTIVE COMPARATOR

Participants 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).

Drug: Norepinephrine intravenous infusion

Interventions

Vasopressin intravenous infusion DRUG

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.

Also known as: Arginine Vasopressin, ADH, Pitressin

Vasopressin

Norepinephrine intravenous infusion DRUG

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.

Also known as: Noradrenaline, Levophed

Noradrenaline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Pregnancy or breastfeeding.
• Aortic surgery.
• Surgeries to correct congenital heart disease.
• Heart transplants.
• Emergency surgery.
• Use of vasopressor therapy in the preoperative period.
• 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.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Hospital Universitário Cassiano Antônio de Moraes/HUCAM: collaborator
• Hospital Santa Casa de Misericórdia de Vitória: collaborator

Study Sites (1)

Instituto do Coração HCFMUSP

São Paulo, 05403-000, Brazil

RECRUITING

Related Publications (21)

• 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.

  PMID: 26558621 BACKGROUND

• 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.

  PMID: 24621650 BACKGROUND

• 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.

  PMID: 12732600 BACKGROUND

• 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.

  PMID: 29452808 BACKGROUND

• 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.

  PMID: 20670424 BACKGROUND

• 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.

  PMID: 22508204 BACKGROUND

• 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.

  PMID: 24993769 BACKGROUND

• 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.

  PMID: 18305265 BACKGROUND

• 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.

  PMID: 12645718 BACKGROUND

• 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.

  PMID: 29801010 BACKGROUND

• 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.

  PMID: 28057037 BACKGROUND

• 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.

  PMID: 25029144 BACKGROUND

• 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.

  PMID: 27841822 BACKGROUND

• 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.

  PMID: 28915214 BACKGROUND

• 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.

  PMID: 18496368 BACKGROUND

• Levy B, Fritz C, Tahon E, Jacquot A, Auchet T, Kimmoun A. Vasoplegia treatments: the past, the present, and the future. Crit Care. 2018 Feb 27;22(1):52. doi: 10.1186/s13054-018-1967-3.

  PMID: 29486781 BACKGROUND

• Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000 Dec;52(4):595-638.

  PMID: 11121511 BACKGROUND

• Gomes WJ, Carvalho AC, Palma JH, Goncalves I Jr, Buffolo E. Vasoplegic syndrome: a new dilemma. J Thorac Cardiovasc Surg. 1994 Mar;107(3):942-3. No abstract available.

  PMID: 8127127 BACKGROUND

• Bolliger D, Erb JM. Vasopressin-Magic Bullet in Vasoplegia Syndrome After Cardiac Surgery? J Cardiothorac Vasc Anesth. 2018 Oct;32(5):2233-2235. doi: 10.1053/j.jvca.2018.06.006. Epub 2018 Jun 20. No abstract available.

  PMID: 30005847 BACKGROUND

• Levin RL, Degrange MA, Bruno GF, Del Mazo CD, Taborda DJ, Griotti JJ, Boullon FJ. Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery. Ann Thorac Surg. 2004 Feb;77(2):496-9. doi: 10.1016/S0003-4975(03)01510-8.

  PMID: 14759425 BACKGROUND

• Zeng LA, Hwang NC. Vasoplegia: More Magic Bullets? J Cardiothorac Vasc Anesth. 2019 May;33(5):1308-1309. doi: 10.1053/j.jvca.2019.01.010. Epub 2019 Jan 4. No abstract available.

  PMID: 30709595 BACKGROUND

Related Links

• Morais, V D. Vasopressor Agents in Vasoplegic Syndrome after Cardiac Surgery: Systematic Review and Meta-Analysis of Multiple Treatments \[thesis\]. Porto Alegre: Federal University of Rio Grande do Sul; 2014 \[cited 2019-05-25\].

MeSH Terms

Conditions

Shock, Cardiogenic; Postoperative Complications

Interventions

Arginine Vasopressin; Vasopressins; Norepinephrine

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Shock

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Biogenic Monoamines; Biogenic Amines; Catecholamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Ludhmila A Hajjar, Full Professor

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Central Study Contacts

José León

CONTACT

+55 (11) 2661-5795; aro@incor.usp.br

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study is double-blinded. Vasopressin and norepinephrine solutions will be prepared by the pharmacy in identical intravenous bags, labeled only with the participant's identification code. The pharmacy team will be the only party unblinded to treatment allocation. All other clinical staff, investigators, research personnel, participants, and their families will remain blinded throughout the study period.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: April 11, 2025
• First Posted: April 18, 2025
• Study Start: April 1, 2024
• Primary Completion: July 30, 2025
• Study Completion: July 30, 2025
• Last Updated: April 30, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)