- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05230966
Immunometabolic Pattern of Intermittent Hypoxia During ST-segment Elevation Myocardial Infarction
Immunometabolic Pattern of Intermittent Hypoxia as a Protective Mechanism Against Lethal Reperfusion Injury in Patients With ST-segment Elevation Myocardial Infarction
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Koraljka Benko, MD
- Phone Number: +38598462387
- Email: bkoraljka@yahoo.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
For group 1:
- Acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
- Monovascular disease, preocclusive stenosis with TIMI(thrombolysis in myocardial infarction) > 1 on the left main or anterior descending branch of the left coronary artery
- Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm
For group 2:
- 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
- Symptoms of angina pectoris preceding acute myocardial infarction
- Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
- After opening the artery and setting the stent TIMI> 2 flow
- Visually estimated epicardial coronary artery diameter up to 2.5 mm to 4.0 mm
For groups 3 and 4:
- 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
- No symptoms of angina pectoris preceding acute myocardial infarction
- Monovascular disease, occlusion or preocclusive stenosis of the anterior descending branch of the left coronary artery with TIMI <1 flow in STEMI;
- After opening the artery and stent placement TIMI> 2 flow
- Visually estimated diameter of the epicardial coronary artery from 2.5 mm to 4.0 mm
For all groups:
- Age of patients over 18 years
- Signed written informed consent to be included in the survey
Exclusion Criteria:
- Cardiac arrest before or after PCI;
- Cardiogenic shock;
- Previous myocardial infarction or revascularization of the heart;
- Anginal pain before the onset of STEMI in patients to be subjected to RIC;
- Patients with end-stage renal or hepatic disease, diabetics with developed micro and macrovascular complications, oncology patients;
- Significant collaterals in the area of the occluded artery (Rentrop gradus> 1);
- Previous use of nitrates and corticosteroids;
- Pregnant or breastfeeding women;
- Iodine allergy (contrast media);
- Increase in body temperature > 37.5 ° C
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
No Intervention: Group 1- angina pectoris
Patients with acute coronary syndrome; angina pectoris (chest pain with negative troponin T with or without changes in electrocardiographic findings);
|
|
No Intervention: Group 2 - angina pectoris + STEMI+ PCI
Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and preceding symptoms of angina pectoris with primary percutaneous coronary intervention.
|
|
Active Comparator: Group 3 - without angina pectoris + STEMi + RIC + PCI
Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention during which it's carried out remote ischemic conditioning (RIC)
|
RIC is a non-invasive method that achieves a state of intermittent hypoxia, and is performed by inflating the cuff of the pressure gauge on the left upper arm to 200 mmHg in 4 episodes of five-minute ischemia and reperfusion alternately for 45 minutes.
|
No Intervention: Group 4 - without angina pectoris + STEMI + PCI
Patients with acute myocardial infarction with ST-segment elevation, < 6 hours from the onset of chest pain and without preceding symptoms of angina pectoris with primary percutaneous coronary intervention.
|
|
Active Comparator: Group 5 - healthy + RIC
healthy volunteers of the same age and sex, whose samples will be taken after the RIC procedure
|
RIC is a non-invasive method that achieves a state of intermittent hypoxia, and is performed by inflating the cuff of the pressure gauge on the left upper arm to 200 mmHg in 4 episodes of five-minute ischemia and reperfusion alternately for 45 minutes.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Measurement of the concentration and dynamics of troponin T (Trop T)
Time Frame: 24 hour
|
Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of cardiac myosin binding protein C (cMyBP-C)
Time Frame: 24 hour
|
Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of creatine kinase-MB (CK-MB)
Time Frame: 24 hour
|
Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of oxidation/mitochondrial parameter, hypoxia-induced factor 1 alpha (HIF 1α)
Time Frame: 24 hour
|
serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of metabolic parameter, glycine
Time Frame: 24 hour
|
Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of metabolic parameter, kynurenine
Time Frame: 24 hour
|
Serum concentrations (μmol/l) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of metabolic parameter, succinate
Time Frame: 24 hour
|
Serum concentrations (μM) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of immunological parameter, interleukin 1 beta (IL-1 beta)
Time Frame: 24 hour
|
Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of immunological parameter, transforming growth factor beta (TGF beta)
Time Frame: 24 hour
|
Serum concentrations (ng/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Measurement of the concentration and dynamics of immunological parameter, monocyte chemoattraction protein 1 (MCP-1)
Time Frame: 24 hour
|
Serum concentrations (pg/ml) will be measured at four time points 0. - after coronary angiography and before PCI; 1. - 1 hour after PCI; 2. - 12 hours after PCI and 3. - 24 hours after PCI.
|
24 hour
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The changes in serum values of immunometabolic parameters and creatine kinase-MB
Time Frame: 24 hour
|
The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage creatine kinase-MB.
|
24 hour
|
The changes in serum values of immunometabolic parameters and troponin T
Time Frame: 24 hour
|
The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with a degree of tissue damage troponin T
|
24 hour
|
The changes in serum values of immunometabolic parameters and left heart ejection fraction
Time Frame: 7 day
|
The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with functional assessment of the heart muscle, ejection fraction (%).
|
7 day
|
The changes in serum values of immunometabolic parameters in PCI groups and angina pectoris (AP) group
Time Frame: 24 hour
|
The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the data of patients diagnosed with angina pectoris (AP).
|
24 hour
|
The changes in serum values of immunometabolic parameters in PCI groups and the group of healthy volunteers
Time Frame: 24 hour
|
The data of immunometabolic parameters at baseline and during follow up period (measured at 0, 1, 12 and 24 hours after the intervention) in three groups of patients with PCI will be compared with the group of healthy volunteers in whom the RIC method was used.
|
24 hour
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Koraljka Benko, MD, CHC Rijeka; Croatia
Publications and helpful links
General Publications
- 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.
- Hausenloy DJ. Cardioprotection techniques: preconditioning, postconditioning and remote conditioning (basic science). Curr Pharm Des. 2013;19(25):4544-63. doi: 10.2174/1381612811319250004.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Myocardial Ischemia
- Heart Diseases
- Cardiovascular Diseases
- Vascular Diseases
- Postoperative Complications
- Signs and Symptoms, Respiratory
- Cardiomyopathies
- Myocardial Infarction
- Infarction
- ST Elevation Myocardial Infarction
- Reperfusion Injury
- Myocardial Reperfusion Injury
- Hypoxia
Other Study ID Numbers
- 2170-29-02/1-21-2
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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