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

Sponsor

University of Sao Paulo (Other)

Overall Status

Unknown status

CT.gov ID

NCT03483753

Collaborator

(none)

338

Enrollment

Arms

Anticipated Duration (Months)

Study Details

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

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Jan 1, 2019

Anticipated Primary Completion Date :

Jul 1, 2019

Anticipated Study Completion Date :

Jul 1, 2020

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 Names: 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 Names: Blinded Norepinephrine

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 Names:

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 Names:

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 [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 [30 days after randomization]
mortality rate of any cause
Acute myocardial infarction [30 days after randomization]
to compare between groups the incidence of acute myocardial infarction
Cardiogenic shock [30 days after randomization]
to compare between groups the incidence of cardiogenic shock
Ventricular and / or supraventricular arrhythmia [30 days]
to compare between groups the incidence of Ventricular and / or supraventricular arrhythmia
Acute respiratory distress syndrome (ARDS) [30 days]
to compare between groups the incidence of Acute respiratory distress syndrome (ARDS)
Stroke and transient ischemic attack [30 days]
to compare between groups the incidence of Stroke and transient ischemic attack
Delirium [30 days]
to compare between groups the incidence of Delirium
Acute renal failure (AKIN 1 or more) [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 [30 days]
Length of time in the Intensive Care Unit (ICU) and hospital
Length of mechanical ventilation [30 days]
Length of mechanical ventilation
Septic shock [30 days]
to compare between groups the incidence of septic shock
hospital and ICU readmission rate [30 days]
hospital and ICU readmission rate
Reoperation [30 days]
number of patients who required reoperation
Incidence of severe adverse events [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.