A Monocentric Study Assessing the Efficacy of the Nitrosylated Hemoglobin as Biomarker for Detecting the Development of a Cardiovascular Complication During or After Surgery (PICA)

Cardiovascular diseases are the first mortality cause in Occidental countries. Surgery and anesthesia can provoke hemodynamic instability and stimulation of the sympathetic nervous system as well as bleeding or thrombosis. These factors as top of some post-operative factors such as tissular hypoxemia, can result in cardiovascular complications. Developing a tool to predict post-operative cardiovascular complication could influence peri-operative measures by stratifying the population at risk. UCLouvain has developed a patented technique using a paramagnetic electronic resonance spectrometry (EPR) able to quantify a paramagnetic component, nitrosylated hemoglobin (HbNO) of the erythrocytes drawn from venous blood. This HbNO has been correlated to the traditional cardiac risk factors. In this study, we will assess the HbNO of patients prior to surgery and will correlate it with cardiovascualr and non cardiovascular complications in order to evaluate the predictive aspect of our biomarker.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Complications
• Intervention / Treatment: Diagnostic test: Blood sampling for HbNO assessment

Detailed Description

Cardiovascular diseases are the first mortality cause in Occidental countries. They would be the cause of 31% of the overall mortality in those countries.

Some risk factors are strongly related to the apparition of a cardiovascular disease, including smoking, high cholesterol levels, hypertension, diabetes, age, high BMI or familial early cardiovascular disease and/or hypercholesterolemia.

Multiple studies have already shown that major non-cardiac surgery can lead to cardiovascular complications in 3% of the patients regardless of their cardiovascular risk profile and major adverse cardiovascular events are a significant source of post-operative morbidity in approximately 11% among those patient3,4,6,7. Complications can also lead to a prolongated hospitalization for patients undergoing major non-cardiac surgery8,9.The peri- and post-operative cardiovascular complications depend on patient-related risk factors.

Surgery and anesthesia can provoke hemodynamic instability and stimulation of the sympathetic nervous system. Surgery and the ensuing inflammation can also induce bleeding and or thrombosis. These factors as top of some post-operative factors such as tissular hypoxemia, can result in cardiovascular complications.

An assessment of the medical cardiac history of the patients is performed before any surgery3. Developing a tool to predict post-operative cardiovascular complication could influence peri-operative measures by stratifying the population at risk.

It is known that cardiovascular diseases are preceded by a dysfunction of the vascular endothelium leading to a loss of the antithrombogenic, anti-proliferative and vasorelaxant functions.

A key mediator of vascular homeostasis and endothelial integrity is the nitric oxide (NO) produced by the endothelial NO synthetase (eNOS). UCLouvain has developed a patented technique using a paramagnetic electronic resonance spectrometry (EPR) able to quantify a paramagnetic component, nitrosylated hemoglobin (HbNO) of the erythrocytes drawn from venous blood. This HbNO has been correlated to the traditional cardiac risk factors.

Quantifying the HbNO could predict, prior to any major non-cardiac surgery, an eventual peri-operative cardiovascular complication. Preoperative HbNO would as such be a useful marker of cardiovascular complications. Necessary perioperative measures can therefore be taken in order to decrease this risk. This assessment would be associated to the preoperative anesthesia visit (EPI : évaluation péri-interventionnelle) form reporting previous cardiovascular events and risk factors.

• Study Type: Interventional
• Enrollment (Anticipated): 2500
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St Luc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age between 18 and 100 years
• Written informed consent
• For subjects unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the subject has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the subject.
• Forthcoming major surgery + one of the following:

At least one risk factor for cardiovascular disease:

SCORE > 1% and < 5% BMI > 30 Age > 55 years BP: >130 SBP and/or >85 DBP Diabetes type 1 or 2 Active smoker regardless of age Shorteness of breath after climbing 20 stairs Familial early CV disease (<50 years for men; <55 years for women) Familial hypercholesterolemia (segregation of hypercholesterolemic trait or proven genetic mutation at heterozygous or homozygous state)

• LEE score >2
• Thrombophilia: Factor V Leiden
• Flap surgery
• Surgery for liver or kidney graft
• Known cause (i.e. COPD) of respiratory dysfunction; patients under positive pressure (CPAP) treatment
• Sleep apnea syndrome
• Pregnant women at risk of pre-eclampsia: > 20 weeks of pregnancy and one of the following:

SBP > 160 mmHg DBP > 110 mmHg Rise of SBP > 30 mmHg compared to baseline value Rise of DBP > 10 mmHg compared to baseline value Proteinuria ≥ 30 mg/L

o Pre-operative creatinine > 130 µmol/L (> 1.5 mg/dL)

Exclusion Criteria:

• Patients undergoing a cardiovascular surgery
• Patients unable to give informed consent (people under legal guardianship)
• Patients placed in an institution by official or court order

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Blood sampling for HbNO assessment	Diagnostic test: Blood sampling for HbNO assessment; Blood sampling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of intra and postoperative cardiovascular complication or degradation within 12 months	Incidence of intra and postoperative cardiovascular complication or degradation within 12 months	12 months
the duration of hospitalization	the duration of hospitalization	12 months
the duration of residence in intensive care	the duration of residence in intensive care	12 months
the need for a follow-up by a cardiologist	the need for a follow-up by a cardiologist	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of a non-cardiovascular complication	Incidence of a non-cardiovascular complication	12 months
the LEE score at first visit	the LEE score at first visit	12 months

Collaborators and Investigators

• Sponsor: Université Catholique de Louvain
• Collaborators: SPINOVIT

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 19, 2019
• First Posted (Actual): June 21, 2019

Study Record Updates

• Last Update Posted (Actual): November 21, 2022
• Last Update Submitted That Met QC Criteria: November 16, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: cardiovascular nitric oxide erythrocyte
• Other Study ID Numbers: PICA V2.2

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