Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery (VANCSIII)

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ClinicalTrials.gov Identifier: NCT03483753

Recruitment Status : Unknown

Verified October 2018 by Tais Felix Szeles, University of Sao Paulo.
Recruitment status was: Not yet recruiting

First Posted : March 30, 2018

Last Update Posted : October 11, 2018

Sponsor:

Information provided by (Responsible Party):

Tais Felix Szeles, University of Sao Paulo

Study Description

Brief Summary:

The purpose of the present study is to evaluate the effect of vasopressin compared to norepinephrine on the clinical complications of patients with vasospastic shock after noncardiac surgeries.

Condition or disease	Intervention/treatment	Phase
Circulatory Shock Non-cardiac Surgery	Drug: Vasopressin Drug: Norepinephrine	Phase 2 Phase 3

Detailed Description:

The Systemic Inflammatory Response Syndrome (SIRS) is a common complication after non-cardiac surgery, impacting negatively on patient outcome and with high incidence rates. Vasoplegic syndrome is the most serious complication of SIRS and can happen after any type of surgery. The etiology of the vasoplegic syndrome has not yet been fully elucidated, but is known to occur more frequently in patients at high surgical risk, submitted to major surgeries, or in the presence of perioperative complications and patients with comorbidities. In this circumstance, the depletion of vasopressin stocks is described, which may contribute to the refractoriness of the shock and the lack of response to the catecholaminergic drugs. The standard treatment of perioperative vasoplegia has been adequate volume replacement and administration of vasopressors, with norepinephrine being the most commonly used. However, it is known that norepinephrine may have deleterious effects on the body and in 20% of patients with vasospastic shock it is ineffective. Previous studies have suggested benefits of adding vasopressin in refractory situations, especially in septic shock. Recently the VANCS study (Vasopressin or norepinephrine in the vasopregic shock after cardiac surgery: double-blind, controlled and randomized study) demonstrated superiority of vasopressin in the reversion of vasoplegic shock after cardiac surgery, as well as a lower incidence of renal insufficiency, atrial fibrillation and shorter hospitalization time. (Anesthesiology. 2017 Jan;126(1):85-93.)

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	338 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	Vasopressin or Norepinephrine in Vasoplegic Shock After Non-cardiac Surgery: a Randomized and Controlled Trial
Estimated Study Start Date :	January 2019
Estimated Primary Completion Date :	July 2019
Estimated Study Completion Date :	July 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Shock

Drug Information available for: Norepinephrine Argipressin Vasopressin

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Vasopressin group Blinded vasopressin	Drug: Vasopressin Blinded Vasopressin will be started if there is persistent hypotension, characterized by mean arterial pressure <65 mmHg after fluid replacement. Continuous infusion of the drug at doses ranging from 0.01 U / min to 0.06 U / min Other Name: Blinded Vasopressin
Active Comparator: Norepinephrine group Blinded norepinephrine	Drug: Norepinephrine Blinded Norepinephrine will be started if there is persistent hypotension, characterized by mean arterial pressure <65 mmHg after fluid replacement. Continuous infusion of the drug at doses ranging from 0.1 mcg / kg / min to 1.0 mcg / kg / min. Other Name: Blinded Norepinephrine

Outcome Measures

Primary Outcome Measures :

Incidence between groups of a composite outcome of all-cause mortality, cardiovascular and renal complications after high-risk non-cardiac surgeries [ Time Frame: 30 days ]
Cardiovascular complications include: stroke, acute myocardial infarction, cardiogenic shock, nonfatal myocardial injury, and ventricular or supraventricular arrhythmias.

Renal complications: Acute renal failure with AKIN stage 1 or higher or renal support therapy.

Secondary Outcome Measures :

All-cause mortality [ Time Frame: 30 days after randomization ]
mortality rate of any cause
Acute myocardial infarction [ Time Frame: 30 days after randomization ]
to compare between groups the incidence of acute myocardial infarction
Cardiogenic shock [ Time Frame: 30 days after randomization ]
to compare between groups the incidence of cardiogenic shock
Ventricular and / or supraventricular arrhythmia [ Time Frame: 30 days ]
to compare between groups the incidence of Ventricular and / or supraventricular arrhythmia
Acute respiratory distress syndrome (ARDS) [ Time Frame: 30 days ]
to compare between groups the incidence of Acute respiratory distress syndrome (ARDS)
Stroke and transient ischemic attack [ Time Frame: 30 days ]
to compare between groups the incidence of Stroke and transient ischemic attack
Delirium [ Time Frame: 30 days ]
to compare between groups the incidence of Delirium
Acute renal failure (AKIN 1 or more) [ Time Frame: 30 days ]
to compare between groups the incidence of Acute renal failure (AKIN 1 or more)
Length of time in the Intensive Care Unit (ICU) and hospital [ Time Frame: 30 days ]
Length of time in the Intensive Care Unit (ICU) and hospital
Length of mechanical ventilation [ Time Frame: 30 days ]
Length of mechanical ventilation
Septic shock [ Time Frame: 30 days ]
to compare between groups the incidence of septic shock
hospital and ICU readmission rate [ Time Frame: 30 days ]
hospital and ICU readmission rate
Reoperation [ Time Frame: 30 days ]
number of patients who required reoperation
Incidence of severe adverse events [ Time Frame: 30 days ]
to compare the incidence of severe adverse outcomes defined as mesenteric ischemia, digital ischemia, hyponatremia (Na<130mEq/L), myocardial infarction or stroke

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age greater than 18 years;
Patients undergoing high-risk non-cardiac surgery;
vasopressor need within 24 hours after surgery, defined as mean arterial pressure (MAP) <65 mmHg after volume resuscitation with at least 1 liter of crystalloid solution (Ringer's lactate) and maintaining a cardiac index> 2.2 ml / min / m²;
Signature of the informed consent form.

Exclusion Criteria:

Allergy to vasoactive drugs;
Previous use of vasopressor;
Gestation;
Presence of Raynaud's phenomenon, altered Allen's test, systemic sclerosis or vasospastic diathesis;
Severe hyponatremia (Na <130 mEq / L);
Acute mesenteric ischemia;
Acute coronary syndrome;
Participation in another study;
Refusal to participate in the study.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03483753

Contacts

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Contact: Tais F Szeles, MD	+5519992859415	taisfelix@usp.br
Contact: Ludhmila A Hajjar, MD, PhD	+55993194401	ludhmila@terra.com.br

Sponsors and Collaborators

University of Sao Paulo

Investigators

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Principal Investigator:	Juliano P Almeida, MD, PhD	University of Sao Paulo
Principal Investigator:	Tais F Szeles, MD	University of Sao Paulo

More Information

Publications of Results:

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.

Takenaka K, Ogawa E, Wada H, Hirata T. Systemic inflammatory response syndrome and surgical stress in thoracic surgery. J Crit Care. 2006 Mar;21(1):48-53; discussion 53-5.

Haga Y, Beppu T, Doi K, Nozawa F, Mugita N, Ikei S, Ogawa M. Systemic inflammatory response syndrome and organ dysfunction following gastrointestinal surgery. Crit Care Med. 1997 Dec;25(12):1994-2000.

Dubin A, Pozo MO, Casabella CA, Pálizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Pálizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13(3):R92. doi: 10.1186/cc7922. Epub 2009 Jun 17.

Other Publications:

Levin MA, Lin HM, Castillo JG, Adams DH, Reich DL, Fischer GW. Early on-cardiopulmonary bypass hypotension and other factors associated with vasoplegic syndrome. Circulation. 2009 Oct 27;120(17):1664-71. doi: 10.1161/CIRCULATIONAHA.108.814533. Epub 2009 Oct 12.

Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med. 2001 Aug 23;345(8):588-95. Review.

Gkisioti S, Mentzelopoulos SD. Vasogenic shock physiology. Open Access Emerg Med. 2011 Jan 6;3:1-6. doi: 10.2147/OAEM.S10388. eCollection 2011. Review.

Teboul JL, Monnet X. Detecting volume responsiveness and unresponsiveness in intensive care unit patients: two different problems, only one solution. Crit Care. 2009;13(4):175. doi: 10.1186/cc7979. Epub 2009 Aug 10.

Brown SM, Lanspa MJ, Jones JP, Kuttler KG, Li Y, Carlson R, Miller RR 3rd, Hirshberg EL, Grissom CK, Morris AH. Survival after shock requiring high-dose vasopressor therapy. Chest. 2013 Mar;143(3):664-671. doi: 10.1378/chest.12-1106.

Morales D, Madigan J, Cullinane S, Chen J, Heath M, Oz M, Oliver JA, Landry DW. Reversal by vasopressin of intractable hypotension in the late phase of hemorrhagic shock. Circulation. 1999 Jul 20;100(3):226-9.

Russell JA, Walley KR, Singer J, Gordon AC, Hébert 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.

Russell JA. Vasopressin, Norepinephrine, and Vasodilatory Shock after Cardiac Surgery: Another "VASST" Difference? Anesthesiology. 2017 Jan;126(1):9-11.

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Responsible Party:	Tais Felix Szeles, PhD student, University of Sao Paulo
ClinicalTrials.gov Identifier:	NCT03483753
Other Study ID Numbers:	62586316.6.0000.0065
First Posted:	March 30, 2018 Key Record Dates
Last Update Posted:	October 11, 2018
Last Verified:	October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No
Product Manufactured in and Exported from the U.S.:	Yes

Keywords provided by Tais Felix Szeles, University of Sao Paulo:


Vasopressin Norepinephrine Post-operative Critical Care

Additional relevant MeSH terms:

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Shock Pathologic Processes Vasopressins Arginine Vasopressin Norepinephrine Adrenergic alpha-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action	Physiological Effects of Drugs Sympathomimetics Autonomic Agents Peripheral Nervous System Agents Vasoconstrictor Agents Hemostatics Coagulants Antidiuretic Agents Natriuretic Agents

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