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

April 25, 2025 updated by: Ludhmila Abrahão Hajjar MD, PhD, University of Sao Paulo

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Estimated)

350

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Brazil
      • São Paulo, Brazil, 05403-000
        • Recruiting
        • Instituto do Coração HCFMUSP
        • Contact:
        • Principal Investigator:
          • Ludhmila A Hajjar, Full Professor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Vasopressin
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
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.
Other Names:
  • Pitressin
  • Arginine Vasopressin
  • ADH
Active Comparator: Noradrenaline
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
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.
Other Names:
  • Levophed
  • Noradrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in inotropic function assessed by cardiac output between T0 and T1
Time Frame: Up to 1 hour after initiation of vasopressor therapy
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in left ventricular ejection fraction (LVEF) between T0 and T1
Time Frame: Up to 1 hour after vasopressor initiation
LVEF will be measured using transthoracic echocardiography at T0 (baseline) and T1 (after achieving MAP ≥65 mmHg), to assess changes in left ventricular systolic function.
Up to 1 hour after vasopressor initiation
Time to achieve target mean arterial pressure (MAP ≥65 mmHg)
Time Frame: Up to 1 hour
Time (in minutes) between the start of vasopressor infusion (T0) and the point at which MAP ≥65 mmHg is reached (T1), indicating hemodynamic stabilization.
Up to 1 hour
Change in heart rate (HR) between T0 and T1
Time Frame: Up to 1 hour
Heart rate will be measured at baseline (T0) and after stabilization (T1) to assess the chronotropic effect of each drug.
Up to 1 hour
Change in arterial lactate levels between T0 and T1
Time Frame: Up to 1 hour
Arterial lactate will be used as a marker of tissue perfusion, measured at T0 and T1, to evaluate response to vasopressor therapy.
Up to 1 hour
Change in central venous oxygen saturation (SvO₂)
Time Frame: Up to 1 hour
SvO₂ will be measured at T0 and T1 as an indirect marker of oxygen delivery and cardiac output adequacy.
Up to 1 hour
Change in CO₂ gap (central venous-to-arterial CO₂ difference)
Time Frame: Up to 1 hour
The CO₂ gap will be evaluated at T0 and T1 to assess tissue hypoperfusion and response to vasopressor use.
Up to 1 hour
Need for additional open-label norepinephrine
Time Frame: During initial vasopressor titration (up to 1 hour)
Number of participants in each arm requiring additional norepinephrine outside the study drug to reach MAP ≥65 mmHg.
During initial vasopressor titration (up to 1 hour)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Collaborators

Hospital Universitário Cassiano Antônio de Moraes/HUCAM
Hospital Santa Casa de Misericórdia de Vitória

Investigators

  • Principal Investigator: Ludhmila A Hajjar, Full Professor, University of Sao Paulo

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2024

Primary Completion (Estimated)

July 30, 2025

Study Completion (Estimated)

July 30, 2025

Study Registration Dates

First Submitted

April 11, 2025

First Submitted That Met QC Criteria

April 11, 2025

First Posted (Actual)

April 18, 2025

Study Record Updates

Last Update Posted (Actual)

April 30, 2025

Last Update Submitted That Met QC Criteria

April 25, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16286719.1.0000.8069

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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