Clinical trial NCT06934798: Inotropic Effects of Vasopressin Versus Noradrenaline In Patients With Vasoplegic Syndrome After Cardiac Surgery
Official title: Inotropic Effects of Vasopressin Versus Noradrenaline In Patients With Vasoplegic Syndrome After Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Vasoplegic Syndrome of Cardiac Surgery
Keywords: Shock Cardiogenic
Postoperative Complications
Cardiac Surgical Procedures
Lead sponsor: University of Sao Paulo
Sponsor class: OTHER
Collaborators: name: Hospital Universitário Cassiano Antônio de Moraes/HUCAM
name: Hospital Santa Casa de Misericórdia de Vitória
First posted: 2025-04-18
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Change in inotropic function assessed by cardiac output between T0 and T1
timeFrame: Up to 1 hour after initiation of vasopressor therapy
Secondary outcomes:
measure: Change in left ventricular ejection fraction (LVEF) between T0 and T1
timeFrame: Up to 1 hour after vasopressor initiation
measure: Time to achieve target mean arterial pressure (MAP ≥65 mmHg)
timeFrame: Up to 1 hour
measure: Change in heart rate (HR) between T0 and T1
timeFrame: Up to 1 hour
measure: Change in arterial lactate levels between T0 and T1
timeFrame: Up to 1 hour
measure: Change in central venous oxygen saturation (SvO₂)
timeFrame: Up to 1 hour
measure: Change in CO₂ gap (central venous-to-arterial CO₂ difference)
timeFrame: Up to 1 hour
measure: Need for additional open-label norepinephrine
timeFrame: During initial vasopressor titration (up to 1 hour)
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Coração HCFMUSP
Study officials:
affiliation: University of Sao Paulo
name: Ludhmila A Hajjar, Full Professor
role: PRINCIPAL_INVESTIGATOR
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