Cardiogenic Shock Integrated PHenotyping for Event Reduction (CIPHER)

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Diagnostic test: ELISA

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.

• Study Type: Observational
• Enrollment (Anticipated): 26

Contacts and Locations

• Study Contact: Name: nuccia Morici, MD; Phone Number: 2643 +39026444; Email: nuccia.morici@ospedaleniguarda.it
• Study Contact Backup: Name: Alice Sacco, MD; Phone Number: 2567 +39026444; Email: alice.sacco@ospedaleniguarda.it

Study Locations

• Italy
  • Milano, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
    • Contact: nuccia Morici, MD; Phone Number: 2643 +39026444; Email: nuccia.morici@ospedaleniguarda.it
    • Contact: Alice Sacco, MD; Phone Number: 2576 +39026444; Email: alice.sacco@ospedaleniguarda.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute decompensated heart failure, complicated by cardiogenic shock

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Acute decompensated heart failure; patients admitted with Acute decompensated heart failure Complicated by cardiogenic shock

Diagnostic test: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Value of Interleukin 6 (IL-6)	Markers of inflammation. Unit of measure: pg/mL.	3 years
Value of Angiopoietin 2 (Ang-2)	Markers of endothelial permeability. Unit of measure: ng/mL.	3 years
Value of Syndecan-1	Endothelial glycocalyx perturbation. Unit of measure: ng/mL.	3 years
Value of Heparan sulfate (HS)	Endothelial glycocalyx perturbation: Unit of measure: ug/mL.	3 years
Metabolomics profiling	Exporatory assessment of targeted metabolomics through the quantification of almost 180 molecules, including acylcarnitines, amino acids and biogenic amines, hexoside, sphingolipids and glycerophospholipids.	3 years

Collaborators and Investigators

• Sponsor: Niguarda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: March 11, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Metabolomics; heart failure; cardiogenic shock; endothelial glycocalyx; Angiopoietin (Ang)-2
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Shock; Myocardial Infarction; Infarction; Heart Failure; Shock, Cardiogenic
• Other Study ID Numbers: 43-12022020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No