The Role of Inflammation in Myocardial Infarction (INFINITY)

The Complex Role of the Inflammation Response Following an Acute Myocardial Infarction: the INFINITY (INFlammatIoN amI sTudY)

The aim of this research is to study the prognostic role of a selected combination of cytokines and adipokines in patients with myocardial infarction, as well as to determine their role in the development of adverse cardiac remodeling.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction

Detailed Description

After an acute myocardial infarction (AMI) the inflammatory response seems to have a central role and is connected to major adverse outcomes such as ischemia-reperfusion injury, adverse cardiac remodeling, infarct size, and poor prognosis. The concept of monitoring inflammatory markers as predictors of post-myocardial prognosis is gaining more momentum. Finding the appropriate inflammatory biomarker that would serve as a prognostic marker after an AMI and could stratify the risk for adverse outcomes, could be extremely useful.

INFINITY is a multi-center, prospective, observational cohort study, aiming to assess the complex role of inflammation in the post-AMI period. The study plans to include 120 consecutive patients above 18 years old admitted to the four centers participating in the study.

A panel of inflammatory cytokines and adipokines will be recorded. A venous blood sample will be collected on patient admission (H0), 6-12 hours after admission (H6-12), 24-48 hours after admission (H24-48), and at the 30-day visit (D30). Blood will be collected for routine laboratory tests, as well as to measure the levels of the cytokines IL-6, IL-10, IL-18, IL-17, and the adipokines leptin, apelin, and chemerin.

60 carefully selected patients will consist of the control group. The control group will consist of individuals to whom the obstructive coronary artery disease would be ruled out either by invasive or non-invasive coronary angiography or by myocardium perfusion SPECT or stress echocardiography. The patient and control group will be matched at baseline by equating certain clinical characteristics of interest between the exposed and unexposed groups.

The study will test the hypothesis that circulating plasma levels of the above inflammatory biomarkers reflect different clinical manifestations of coronary artery disease and correlate with coronary anatomy, the severity of coronary artery disease, and the prognosis in a 6-month follow-up period. Finally, will investigate whether the integration of the above inflammatory biomarkers into the already established prognostic risk stratification model, GRACE score, could further improve its predictive power.

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Andreas Mitsis, MD, MSc; Phone Number: +35796705559; Email: andymits7@gmail.com

Study Locations

• Cyprus
  • Nicosia, Cyprus, 2029
    • Recruiting
    • Nicosia General Hospital
    • Contact: Andreas Mitsis, MD, MSc; Phone Number: +35796705559; Email: andymits7@gmail.com
    • Principal Investigator: Andreas Mitsis, MD, MSc
    • Sub-Investigator: Panayiotis Avraamides
• Greece
  • Thessaloniki, Greece
    • Not yet recruiting
    • 1st University Department of Cardiology - AHEPA University Hospital
    • Principal Investigator: Antonios Ziakas, MD, PHD
  • Thessaloniki, Greece
    • Not yet recruiting
    • 2nd University Department of Cardiology
    • Principal Investigator: George Kassimis, MD, PHD
  • Thessaloniki, Greece
    • Not yet recruiting
    • 3rd University Department of Cardiology
    • Principal Investigator: Stergios Tzikas, MD, PHD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with acute coronary syndromes (ST-ACS, NSTE-ACS, UA), who underwent coronary angiography.

Description

Inclusion Criteria:

1. ACS (ST-ACS, NSTE-ACS, UA) referred for coronary angiography
2. Above 18 years old
3. Consent form obtained

Exclusion Criteria:

1. Chronic Renal Failure (CRF) stage IV (e GFR < 29 ml/min or creatinine > 2 mg/dl)
2. Chronic Liver Disease (CLD) (ALT > 2 times upper normal limit)
3. Chronic Inflammation and/or autoimmune diseases
4. Active Ca
5. Recent CVA (less than 1 month)
6. Recent (within 2 weeks) use of glucocorticoid drugs or immunosuppressive agents
7. Acute or chronic infection, major surgery, or trauma in the last month
8. Previous heart transplantation
9. Poor life expectancy
10. Cardiogenic shock
11. Cardiac arrest

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients Group; The study plans to include 120 consecutive patients above 18 years old presenting with STEMI, NSTEMI, or UA and referred for coronary angiography.
Control Group; 60 patients will consist of the control group. The patient and control group will be matched at baseline by equating certain clinical characteristics of interest between the exposed and unexposed groups. The control group will consist of individuals to whom the obstructive coronary artery disease would be ruled out either by invasive or non-invasive coronary angiography or by myocardium perfusion SPECT or stress echocardiography.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Mortality	The relationship between the levels of each biomarker (peak H24-48 measurement and area under curve based on the pharmacokinetics of each biomarker based on H0, H6-12, H24-48, and D30 post-enrollment measurements) with all-cause 6-month mortality (cardiac and non-cardiac mortality)	6-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of heart failure	The relationship between the levels of each biomarker (peak measurement H24-48 and area under curve based on the pharmacokinetics of each biomarker based on measurements H0, H6-12, H24-48, and D30 post-enrollment) with the development of heart failure within a follow-up interval of 6 months after enrollment.	6-months
Incidence of MACE	The relationship between the levels of each biomarker (peak measurement H24-48 and area under curve based on the pharmacokinetics of each biomarker based on measurements H0, H6-12, H24-48, and D30 post-enrollment) with 6-month MACEs (non-fatal MI, unplanned repeated revascularization, acute heart failure or angina/ACS requiring rehospitalization, sudden cardiac death).	6-months
Change in cytokines and adipokines (pg/mL)	The comparison between the values of the studied biomarkers at the four-time intervals (H0, H6-12, H24-48, D30).	6-months
Change in the left ventricular end-diastolic volume index (percent)	Change in the left ventricular end-diastolic volume index (percent) is assessed in patients with myocardial infarction at 6-months follow-up with intermediate assessments at day 7 after onset	6-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in IL-6	The comparison between the values of IL-6 at the four-time intervals (H0, H6-12, H24-48, D30).	30-days
Change in IL-10	The comparison between the values of IL-10 at the four-time intervals (H0, H6-12, H24-48, D30).	30-days
Change in IL-18	The comparison between the values of IL-18 at the four-time intervals (H0, H6-12, H24-48, D30).	30-days
Change in IL-17	The relationship between the levels of IL-17 (peak H24-48 measurement and area under curve based on the pharmacokinetics of each biomarker based on H0, H6-12, H24-48, and D30 post-enrollment measurements) with all-cause 6-month mortality (cardiac and non-cardiac mortality).	30-days
Change in Leptin	The comparison between the values of Leptin at the four-time intervals (H0, H6-12, H24-48, D30).	30-days
Change in Apelin	The comparison between the values of Apelin at the four-time intervals (H0, H6-12, H24-48, D30).	30-days
Change in Chemerin	The comparison between the values of Chemerin at the four-time intervals (H0, H6-12, H24-48, D30).	30-days

Collaborators and Investigators

• Sponsor: Nicosia General Hospital
• Collaborators: Aristotle University Of Thessaloniki; Hippocration General Hospital
• Investigators: Principal Investigator: George Kassimis, MD, PhD, Second Department of Cardiology, Aristotle University of Thessaloniki; Study Director: Stergios Tzikas, MD, PhD, Third Department of Cardiology, Aristotle University of Thessaloniki; Study Director: Antonios Ziakas, MD, PhD, First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki; Study Director: Andreas Mitsis, MD, MSc, Nicosia General Hospital

Publications and helpful links

General Publications

• Mitsis A, Kadoglou NPE, Lambadiari V, Alexiou S, Theodoropoulos KC, Avraamides P, Kassimis G. Prognostic role of inflammatory cytokines and novel adipokines in acute myocardial infarction: An updated and comprehensive review. Cytokine. 2022 May;153:155848. doi: 10.1016/j.cyto.2022.155848. Epub 2022 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): May 30, 2025

Study Registration Dates

• First Submitted: September 26, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Inflammation; Prognosis; STEMI; Adipokines; Cytokines; NSTEMI; Unstable Angina
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Inflammation
• Other Study ID Numbers: DD5025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We plan to share IPD because the sharing of clinical trial data can increase transparency, improve understanding of individual trials, and facilitate the re-use of the data for secondary research, including meta-analyses of individual participant data (IPD meta-analyses).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No