Clinical trial NCT05230966: Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction
Official title: Immunometabolic Pattern of Intermittent Hypoxia as a Protective Mechanism Against Lethal Reperfusion Injury in Patients With ST-segment Elevation Myocardial Infarction
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Myocardial Ischemic-reperfusion Injury
Lead sponsor: Clinical Hospital Center Rijeka
Sponsor class: OTHER
First posted: 2022-02-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The aim of this study is to characterize the protective pattern of intermittent hypoxia, angina pectoris and remote ischemic conditioning, in reperfusion injury by determining and monitoring the plasma immunometabolic parameters of patients with STEMI. This could contribute to better understanding of this phenotypic pattern with translation into clinical practice.

Detailed description: In acute myocardial infarction with ST segment elevation (STEMI), lethal reperfusion injury of the myocardium, caused by percutaneous coronary intervention (PCI), represents additional and irreversible damage due to ischemic heart muscle reperfusion that contributes to the final size of the infarct zone by up to 50%. The size of the infarcted area is the major determinant for the long-term prognosis and heart failure progression in patients with STEMI. Cardioprotection from ischemic - reperfusion myocardial injury (MIRI) can be regulated by its own innate physiological adaptive mechanisms like intermittent hypoxia achieved by the method of conditioning that includes short sublethal ischemic and reperfusion episodes.

The known natural clinical equivalent of intermittent hypoxia and the starting point in understanding the underlying mechanism is angina pectoris (AP).

Intermittent hypoxia is a protective mechanism against heart ischemic-reperfusion injury with reduced tissue damage and consequently better outcome in patients with STEMI. For the purpose of this work, a cardioprotective pattern was defined that includes immunometabolic factors as parameters for assessing the state of intermittent hypoxia on which the success of the application of the method of remote ischemic conditioning (RIC) is based.

Eligibility criteria: Inclusion Criteria:

For group 1:

1. Acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
2. Monovascular disease, preocclusive stenosis with TIMI(thrombolysis in myocardial infarction) \> 1 on the left main or anterior descending branch of the left coronary artery
3. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For group 2:

1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation\> 0.1 mV in two or more leads, or\> 0.2 mV in V1-V3) \<6 hours from the onset of chest pain
2. Symptoms of angina pectoris preceding acute myocardial infarction
3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI \<1 flow in STEMI;
4. After opening the artery and setting the stent TIMI\> 2 flow
5. Visually estimated epicardial coronary artery diameter up to 2.5 mm to 4.0 mm

For groups 3 and 4:

1. Acute myocardial infarction with ST-segment elevation (ST-segment elevation\> 0.1 mV in two or more leads, or\> 0.2 mV in V1-V3) \<6 hours from the onset of chest pain
2. No symptoms of angina pectoris preceding acute myocardial infarction
3. Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI \<1 flow in STEMI;
4. After opening the artery and stent placement TIMI\> 2 flow
5. Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm

For all groups:

1. Age of patients over 18 years
2. Signed written informed consent to be included in the survey

Exclusion Criteria:

1. Cardiac arrest before or after PCI;
2. Cardiogenic shock;
3. Previous myocardial infarction or revascularization of the heart;
4. Anginal pain before the onset of STEMI in patients to be subjected to RIC;
5. Patients with end-stage renal or hepatic disease, diabetics with developed micro and macrovascular complications, oncology patients;
6. Significant collaterals in the area of the occluded artery (Rentrop gradus\> 1);
7. Previous use of nitrates and corticosteroids;
8. Pregnant or breastfeeding women;
9. Iodine allergy (contrast media);
10. Increase in body temperature \> 37.5 ° C
11. Participation in another clinical trial

Randomly selected (coin toss) patients will be randomized to group 3 and 4, respectively, for percutaneous coronary intervention with or without RIC

Primary outcomes:
measure: Measurement of the concentration and dynamics of troponin T (Trop T)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of cardiac myosin binding protein C (cMyBP-C)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of creatine kinase-MB (CK-MB)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of oxidation/mitochondrial parameter, hypoxia-induced factor 1 alpha (HIF 1α)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of metabolic parameter, glycine
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of metabolic parameter, kynurenine
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of metabolic parameter, succinate
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of immunological parameter, interleukin 1 beta (IL-1 beta)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of immunological parameter, transforming growth factor beta (TGF beta)
timeFrame: 24 hour
measure: Measurement of the concentration and dynamics of immunological parameter, monocyte chemoattraction protein 1 (MCP-1)
timeFrame: 24 hour
Secondary outcomes:
measure: The changes in serum values of immunometabolic parameters and creatine kinase-MB
timeFrame: 24 hour
measure: The changes in serum values of immunometabolic parameters and troponin T
timeFrame: 24 hour
measure: The changes in serum values of immunometabolic parameters and left heart ejection fraction
timeFrame: 7 day
measure: The changes in serum values of immunometabolic parameters in PCI groups and angina pectoris (AP) group
timeFrame: 24 hour
measure: The changes in serum values of immunometabolic parameters in PCI groups and the group of healthy volunteers
timeFrame: 24 hour
Other outcomes:
Locations:
Study officials:
affiliation: CHC Rijeka; Croatia
name: Koraljka Benko, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest. 2013 Jan;123(1):92-100. doi: 10.1172/JCI62874. Epub 2013 Jan 2.
citation: Hausenloy DJ. Cardioprotection techniques: preconditioning, postconditioning and remote conditioning (basic science). Curr Pharm Des. 2013;19(25):4544-63. doi: 10.2174/1381612811319250004.
citation: Han X, Jeong MH, Won J, Kim Y, Kim MC, Sim DS, Hong YJ, Kim JH, Ahn Y. Impact of Previous Angina on Clinical Outcomes in ST-Elevation Myocardial Infarction Underwent Percutaneous Coronary Intervention. Chonnam Med J. 2020 May;56(2):136-143. doi: 10.4068/cmj.2020.56.2.136. Epub 2020 May 25.
citation: Heusch G, Botker HE, Przyklenk K, Redington A, Yellon D. Remote ischemic conditioning. J Am Coll Cardiol. 2015 Jan 20;65(2):177-95. doi: 10.1016/j.jacc.2014.10.031.