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

University of Sao Paulo

Status and phase: Enrolling; Phase 4

Conditions: Vasoplegic Syndrome of Cardiac Surgery

Treatments: Drug: Norepinephrine intravenous infusion; Drug: Vasopressin intravenous infusion

Study type: Interventional

Funder types: Other

Identifiers

NCT06934798

16286719.1.0000.8069

Details and patient eligibility

About

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.

Full 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

Enrollment: 350 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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350 participants in 2 patient groups

Vasopressin

Experimental group

Description:

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).

Treatment:

Drug: Vasopressin intravenous infusion

Noradrenaline

Active Comparator group

Description:

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).

Treatment:

Drug: Norepinephrine intravenous infusion