Cardiogenic Shock Integrated PHenotyping for Event Reduction

NCT ID: NCT04323371

Last Updated: 2023-03-22

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 26 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-06-30
• Study Completion Date: 2025-03-01

Brief Summary

The purpose of this study is to better understand the time course of different biological mechanisms involved in acute decompensated heart failure complicated by cardiogenic shock throughout the evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and throughout a targeted metabolomic approach.

Detailed Description

Cardiogenic shock (CS) is a heterogenous syndrome with in-hospital mortality up to 60%, that, unfortunately, has remained stagnant over the time, despite observed improvements with pharmacological and non-pharmacological approach, even though only in terms of haemodynamic stabilization.

While very early mortality in CS is largely related to sudden and severe circulation failure, subsequent death is strongly influenced by activation of neurohumoral and inflammatory response leading to multiorgan failure. Previous studies on CS have almost exclusively been focused on CS following an acute coronary syndrome (ACS). Patients with acutely decompensated heart failure (ADHF) represent a different pathophysiologic phenotype compared with acute coronary syndrome (ACS) patients, which may lead to a differential response to device therapy.

In the face of complex biological phenomena guidelines are incapable of distinguishing the underlying pathophysiological mechanisms and give us input to standardize, whereas there is an unmet need for a personalized medicine.

The evaluation of changes and the relationship among markers of inflammation (IL-6) and markers of increased endothelial permeability (Ang-2) or endothelial glycocalyx perturbation (Syndecan-1 and HS) and an exploratory analysis throughout targeted metabolomics may help us to better understand the time course of different biological mechanisms involved in CS.

Conditions

Heart Failure

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute decompensated heart failure

patients admitted with Acute decompensated heart failure Complicated by cardiogenic shock

ELISA

Intervention Type: DIAGNOSTIC_TEST

Blood and derived fluids will be collected from 26 ADHF CS patients admitted to intensive care at Niguarda Hospital and locally stored.Stocked samples will be shipped to the Central Laboratories at Milano Uni and MilaIFC-CNR for the metabolomic and biomarkers analysis,respectively.To evaluate interleukin-6 (marker of systemic inflammation),angiopoietin-2 (marker of endothelial permeability), syndecan-1 and heparan sulfate (markers of endothelial glycocalyx),2 aliquotes of serum samples will be used by IFC CNR.The biomarkers will be assessed through ELISA analytical techniques, based on the interactions inside a microplate between a primary pre-coated antibody and the specific protein contained in serum samples.A secondary antibody, link to a horseradish peroxidase (HRP) detection system, is able to recognize and bind the antigen, and to produce a colorimetric reaction after the addition of enzyme substrate which is proportional to the amount of the target protein bound

Interventions

ELISA

Blood and derived fluids will be collected from 26 ADHF CS patients admitted to intensive care at Niguarda Hospital and locally stored.Stocked samples will be shipped to the Central Laboratories at Milano Uni and MilaIFC-CNR for the metabolomic and biomarkers analysis,respectively.To evaluate interleukin-6 (marker of systemic inflammation),angiopoietin-2 (marker of endothelial permeability), syndecan-1 and heparan sulfate (markers of endothelial glycocalyx),2 aliquotes of serum samples will be used by IFC CNR.The biomarkers will be assessed through ELISA analytical techniques, based on the interactions inside a microplate between a primary pre-coated antibody and the specific protein contained in serum samples.A secondary antibody, link to a horseradish peroxidase (HRP) detection system, is able to recognize and bind the antigen, and to produce a colorimetric reaction after the addition of enzyme substrate which is proportional to the amount of the target protein bound

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 and < 75, men and women;
• 1) Systolic blood pressure (SBP) < 90mmHg or mean arterial pressure (MAP) < 60 mmHg, after an appropriate fluid challenge if there is no sign of overt fluid overload; OR 2) need of vasoactive agents to maintain SBP > 90 mmHg or MAP > 60 mmHg.
• Reduced ejection fraction (left ventricle systolic function ≤35%).
• Moreover, eligible patients have to fit at least ONE of the following criteria/items of overt hypoperfusion: altered state of consciousness; sweaty and cold skin; mixed venous oxygen saturation < 60%; arterial lactates > 2 mmol/L; oliguria < 0.5 ml/Kg/h for at least 6 hours.
• Eligible patients shouldn't have contraindications to heart replacement therapy (HRT).

Exclusion Criteria

The participant will not be enrolled if ANY of the following criteria will be detected:

• Cardiogenic shock symptoms beyond 6 hours.
• Septic shock with evident septic focus.
• Cardiogenic shock due to acute myocardial infarction.
• Cardiogenic shock due to acute myocarditis.
• Cardiogenic shock due to pulmonary thromboembolism.
• Reiterating major arrhythmias: VT or VF or AF, with ventricular rate > 160 bpm.
• Severe aortic valve disease.
• Obstructive hypertrophic cardiomyopathy or constrictive pericarditis or severe heart failure due to congenital heart disease
• Severe peripheral vascular disease that contraindicates mechanical support insertion.
• Cardiogenic shock secondary to either cardiac or non-cardiac surgery.
• Comorbidities with ominous prognosis (life expectancy < 1 year).
• Estimated glomerular filtration rate severely impaired before enrolment (eGFR<30 ml/min/1.73 m2) or severe chronic obstructive pulmonary disease (COPD) or liver cirrhosis.
• Pregnant, lactating or subjects planning pregnancy during the course of the trial.

Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 74 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Niguarda Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Nuccia Morici, MD

Role: CONTACT

nuccia.morici@ospedaleniguarda.it

+39026444 ext. 2643

Alice Sacco, MD

Role: CONTACT

alice.sacco@ospedaleniguarda.it

+39026444 ext. 2567

Facility Contacts

Nuccia Morici, MD

Role: primary

nuccia.morici@ospedaleniguarda.it

+39026444 ext. 2643

Alice Sacco, MD

Role: backup

alice.sacco@ospedaleniguarda.it

+39026444 ext. 2576

Other Identifiers

43-12022020

Identifier Type: -

Identifier Source: org_study_id