The RESTORE-SIRIO Randomized Controlled Trial

Study Overview
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Brief Summary
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Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion strategy for treating acute ST-segment elevation myocardial infarction (STEMI). The main goals are to restore epicardial infarct-related artery patency and to achieve microvascular reperfusion as early as possible. No-reflow is the term used to describe inadequate myocardial perfusion of a given coronary segment without angiographic evidence of persistent mechanical obstruction of epicardial vessels and it refers to the high resistance of microvascular blood flow encountered during opening of the infarct-related coronary artery. Despite optimal evidence-based PPCI, myocardial no-reflow can still occur, negating many of the benefits of restoring culprit vessel patency, and is associated with a worse in-hospital and long-term prognosis. Several strategies have been tested to revert the no-reflow including the use of thrombectomy, glycoprotein IIb/IIIa inhibitors and the use of intracoronary adenosine, but none has been demonstrated to effectively counteract the phenomenon. The trial aims to show the effect of the administration of intracoronary adrenalin on myocardial reperfusion assessed by magnetic resonance in patients with STEMI undergoing PCI and with persistent coronary angiographic The Thrombolysis in Myocardial Infarction (TIMI) 0-1 flow during the interventional procedure after failure of standard therapy.

Official Title
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Impact of intRacoronary adrEnaline on Myocardial reperfuSion in STEMI paTients With Persistent Impaired cORonary Flow After pErcutaneous Coronary Intervention: the RESTORE-SIRIO Randomized Controlled Trial

Conditions
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Percutaneous Coronary Intervention, No-reflow Phenomen, Acute ST-segment Elevation Myocardial Infarction

Intervention / Treatment
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* Other: intracoronary epinephrine
* Other: no intracoronary epinephrine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age presentation within 6-7 h of symptom onset of STEMI eligibility for reperfusion by primary-PCI TIMI flow grade 0-1 during the interventional procedure in the culprit vessel after the initial opening of the vessel with the coronary wire Exclusion Criteria: evident clinical arrhythmias (ventricular tachycardia/ventricular fibrillation) evidence of coronary dissection or spasm Parkinson symptoms closed angle glaucoma thyroid disorders known history to hypersensitivity to the drug pregnancy stage 4 or 5 CKD (eGFR <30 mL/min/1.73 m2)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: epinephrine<br>intracoronary epinephrine is two ampoules each of 1:1000 epinephrine (1 μg/mL) diluted into 100 mL of normal saline (to 20 μg/mL epinephrine solution); a 5 ml syringe prepared will then contain 100 μg | Other: intracoronary epinephrine<br>* after failure of standard therapy patients will treated with epinephrine<br>|
| Other: no intracoronary epinephrine<br>no epinephrine | Other: no intracoronary epinephrine<br>* patients will receive standard therapy only<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| myocardial infarct size (% total LV mass) | cMRI parameters: myocardial infarct size (% total LV mass) | 48-72 hours post intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and extent of microvascular obstruction | cMRI parameter | 48-72 hours and 30 days post intervention | 
| Myocardial salvage index (MSI) | cMRI parameter | 48-72 hours and 30 days post intervention | 
| Intra-myocardial haemorrhage (IMH) | cMRI parameter | 48-72 hours and 30 days post intervention | 
| LV ejection fraction (LVEF) and volumes | cMRI parameter | 48-72 hours and 30 days post intervention | 
| Thrombolysis in Myocardial Infarction (TIMI) flow grade) | Angiographic markers | 48-72 hours post intervention | 
| Myocardial blush grade (MBG) | Angiographic markers | 48-72 hours post intervention | 
| Computer-assisted myocardial blush quantification using the software 'Quantitative Blush Evaluator' (QuBE) | Angiographic markers | 48-72 hours post intervention | 
| Degree of ST segment resolution on ECG |  | 48-72 hours post intervention |