Analysis of the Efficacy of Cardiac Ischemic Postconditioning With New Clinical End-points Using Novel Biomarkers

Acute Myocardial Infarction With ST Elevation Clinical Trial

Official title:

Evaluation of the Efficacy and Biochemical Characteristics of Ischemic Postconditioning in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04824716
• Other study ID #: IPOST-01, v2.0, Nov 22, 2012
• Status: Completed
• Phase: N/A
• Start date: January 14, 2013
• Est. completion date: October 15, 2018

Study information

• Verified date: April 2021
• Source: Pharmahungary Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: October 15, 2018
• Est. primary completion date: October 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Myocardial Infarction With ST Elevation
• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Procedure:
• Postconditioning
The protocol of primary PCI followed by stenting is executed according to the descriptions according to the majority of relevant scientific literature on postconditioning studies and in accordance with the most recent guidelines. In the post conditioned group, after recanalization, the artery is occluded by inflation of stent balloon (4 times for 1-1 minute) followed by 1-1-minute reperfusion, repeatedly. Eight minutes after the start of examination, angiography is made in order to determine blood flow. Intervention is finished by the operator and another angiographic image is made (identical to initial standard projection).

Device:
• Percutaneous coronary intervention
Percutaneous coronary intervention as per European Society of Cardiology guidelines.

Locations

Country	Name	City	State
Hungary	Heart and Vascular Center, Semmelweis University	Budapest
Hungary	Department of Invasive Cardiology of Cardiology Center, Faculty of Medicine, University of Szeged	Szeged
Hungary	Pharmahungary Group	Szeged

Sponsors (3)

Lead Sponsor	Collaborator
Peter Ferdinandy	Semmelweis University Heart and Vascular Center, Szeged University

Country where clinical trial is conducted

Hungary, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiac magnetic resonance imaging	Left and right ventricular function, myocardial scar, transmurality, diffusion spectrum imaging (DSI) measurement and evaluation	3 months after acute myocardial infarction
Secondary	Echocardiography measurement of Cardiac Ejection Fraction	Measurement of Cardiac Ejection Fraction using Teicholz and Simpson methods on both study arms.	48 hours and 3 months after acute myocardial infarction
Secondary	Echocardiography measurement of cardiac left ventricular segments for wall motion abnormalities	Calculation of cardiac wall motion score index on both study arms.	48 hours and 3 months after acute myocardial infarction
Secondary	Laboratory measurement of blood Nitrotyrosine levels.	Laboratory measurement of Nitrotyrosine levels in blood samples with ELISA on both study arms.	5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
Secondary	Laboratory measurement of blood MMP activity.	Laboratory measurement of MMP activity in blood samples with zymography on both study arms.	5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
Secondary	Laboratory characterization of microRNA patterns with microRNA array	Laboratory characterization of microRNA expression pattern in blood samples with with microRNA array on both study arms.	5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
Secondary	Validation of selected microRNA with quantitative real-time PCR	Out of the differentially expressed microRNAs identified in Outcome 6, up to 10 different miRNAs will be selected for further validation of their specific expression change (expressed by fold-change) by quantitative real-time PCR in up to 10 randomly selected patients on both study arms, respectively.	5 minutes before PCI as well as 8 minutes after, 60 minutes, 6, 12, 24, 48 hours, and 3 months after acute myocardial infarction
Secondary	Electrocardiography ST segment post-procedure evaluation	Distortion in ST segment amplitude in millivolt (mV) and duration measured in milliseconds (ms) after procedure measured by 12-lead Electrocardiography (ECG) will be evaluated on both study arms.	Post-procedure 60, 90 minutes, and 12, 24, 48 hours.
Secondary	Electrocardiography T wave post-procedure evaluation	Distortion in T wave amplitude in millivolt (mV) and duration measured in milliseconds (ms) after procedure measured by 12-lead Electrocardiography (ECG) will be evaluated on both study arms.	Post-procedure 60, 90 minutes, and 12, 24, 48 hours.

External Links

•   Website of Department of Invasive Cardiology of Cardiology Center, Faculty of Medicine, University of Szeged.
•   Website of Pharmahungary Group.
•   Website of Semmelweis University Heart and Vascular Center.