Clinical trial NCT04824716: Analysis of the Efficacy of Cardiac Ischemic Postconditioning With New Clinical End-points Using Novel Biomarkers
Official title: Evaluation of the Efficacy and Biochemical Characteristics of Ischemic Postconditioning in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myocardial Infarction With ST Elevation
Keywords: ischemic postconditioning
acute myocardial infarction
Investigator Initiated Trial
biomarker
coronary artery disease
ischemic
postconditioning
infarction
infarct size
area at risk
coronary occlusion
balloon catheter
percutaneous coronary intervention
PCI
MRI
Lead sponsor: Pharmahungary Group
Sponsor class: INDUSTRY
Collaborators: name: Semmelweis University Heart and Vascular Center
name: Szeged University
First posted: 2021-04-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The aim of the present study was to investigate the efficacy of ischemic postconditioning in acute myocardial infarction patients. The safety of patients enrolled in the study was ensured during the entire study. Over 18 years old men and women were enrolled in the study who arrived to 2 of the most acknowledged Hungarian cardiac centres due to acute myocardial infarction and fulfilled all inclusion and exclusion criteria as per protocol. Patients in the order of their arrival were assigned either to control or post conditioned groups by turns. Medical treatment of the control group was done according to standard Percutaneous Coronary Intervention (PCI) guidelines, i.e. there was no further intervention after artery opening for 8 minutes, then stenting was performed. In the post conditioned group, after reperfusion has been confirmed, the coronary artery was occluded by inflation of the stent balloon 4 times (for 1-1 minute) followed by 1-1-minute reperfusion repeatedly to induce ischemic postconditioning. Postconditioning procedure was followed by stenting as in the control group. All other interventions and treatments in both patient groups were identical according to guidelines.

Detailed description: Over 18 years old men and women were enrolled in the study who arrived to 2 of the most acknowledged Hungarian cardiac centres due to acute myocardial infarction and fulfilled all inclusion and exclusion criteria as per protocol. Patients in the order of their arrival were assigned either to control or post conditioned groups by turns. After closing patient enrolment, further subgrouping will be performed in case sufficient group size has been achieved as follows: (1) normal, control, (2) normal, post conditioned, (3) hypercholesterolemic, not treated with statins, control, (4) hypercholesterolemic, not treated with statins, post conditioned, (5) statin treated, control, (6) statin treated, post conditioned.

Characterisation of postconditioning is performed by the following parameters:

1. Blood tests 5 minutes before as well as 8, 60 minutes, 24 hours, and 3 months after PCI to measure nitrotyrosine, a biomarker of peroxynitrite formation (nitrosative stress) by ELISA; B-type natriuretic peptide, a biomarker of heart failure by ELISA; matrix metalloproteinase activities (MMP-2 and MMP-9) putative biomarkers of cardiac remodelling by zymography; microRNA expression pattern by sequencing and its validation by quantitative real-time polymerase chain reaction (PCR).
2. Routine laboratory tests 6, 12 and 48 hours after PCI including creatine kinase (CKMB) and cardiac troponin T (cTnT).
3. ECG immediately after recanalization and intervention after 60 and 90 minutes, then 12, 24, 36 and 48 hours later 12-lead ECG is registered.
4. Echocardiography: 48 hours after intervention, standard view to judge left ventricle segments movement disorders
5. Angiography: Blush, Syntax score, and ischemic risk zone (area at risk, AAR) are determined
6. cardiac late enhancement magnetic resonance (MR) imaging to determine infarct size

At 3-month follow-up visit the following parameters were measured: echocardiography for restitution assessment, cardiac late enhancement MR imaging to determine infarct size and cardiac function, blood sampling for above mentioned biochemical laboratory tests

Eligibility criteria: Inclusion Criteria:

1. Subject must be \>18 years of age
2. Myocardial infarction with elevated ST
3. Chest pain onset less than 12 hours before PCI
4. concordant ST elevation (\>0,1 mV) in at least 2 ECG leads
5. Occluded main proximal or middle main coronary ('Thrombolysis In Myocardial Infarction' flow grade: 0) diagnosed with coronarography
6. Coronary opened by PCI (TIMI 2 flow grade)
7. Awake, conscious, co-operating patient, who is able to retain his breath for 10 sec
8. Signed Patient Information Leaflet and Patient Informed Consent Form

Exclusion Criteria:

1. Cardiogenic shock
2. Previous myocardial infarction in the area of the occluded coronary artery
3. Occluded coronary with visible collateral branches
4. Lack of co-operation
5. Current left or right bundle branch block (LBBB)
6. Malignant ventricle arrhythmia or atrial fibrillation
7. Killip class \> 2
8. Known renal failure

Primary outcomes:
measure: Cardiac magnetic resonance imaging
timeFrame: 3 months after acute myocardial infarction
Secondary outcomes:
measure: Echocardiography measurement of Cardiac Ejection Fraction
timeFrame: 48 hours and 3 months after acute myocardial infarction
measure: Echocardiography measurement of cardiac left ventricular segments for wall motion abnormalities
timeFrame: 48 hours and 3 months after acute myocardial infarction
measure: Laboratory measurement of blood Nitrotyrosine levels.
timeFrame: 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
measure: Laboratory measurement of blood MMP activity.
timeFrame: 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
measure: Laboratory characterization of microRNA patterns with microRNA array
timeFrame: 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
measure: Validation of selected microRNA with quantitative real-time PCR
timeFrame: 5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
measure: Electrocardiography ST segment post-procedure evaluation
timeFrame: Post-procedure 60, 90 minutes, and 12, 24, 48 hours.
measure: Electrocardiography T wave post-procedure evaluation
timeFrame: Post-procedure 60, 90 minutes, and 12, 24, 48 hours.
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Heart and Vascular Center, Semmelweis University
city: Szeged
country: Hungary
facility: Pharmahungary Group
city: Szeged
country: Hungary
facility: Department of Invasive Cardiology of Cardiology Center, Faculty of Medicine, University of Szeged
Study officials:
affiliation: Heart and Vascular Center, Semmelweis University, Budapest
name: Béla Merkely, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmahungary Group
name: Peter Ferdinandy, MD, PhD, MBA
role: STUDY_DIRECTOR
affiliation: University of Szeged, Faculty of Medicine, Cardiology Center, Department of Invasive Cardiology
name: Imre Ungi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: