Optimal Coronary Flow After PCI for Myocardial Infarction - a Pilot Study

Study Overview
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Brief Summary
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In this study the investigators test the hypothesis that alteplase given intra coronary after PCI reduce infarct size in patients with ST-elevation myocardial infarction(STEMI) and impaired microvascular function defined as a value of index of microvascular resistance (IMR) >30.

Detailed Description
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After coronary stenting, index of microvascular resistance (IMR) will be measured invasively. Patients with IMR >30 will be randomised to 20 mg alteplase or placebo (NaCl) administered in the culprit vessel through a microcatheter. Magnet resonance imaging (MRI) of the myocardium will be performed early (2-6 days) and late (3 months) to estimate the primary endpoint (infarct size). 10 non-randomised patients, with IMR <30, will undergo the same follow-up as the randomised patients. Clinical events for all randomised and non-randomised patients will be collected from Swedish national registries and by telephone at 3 and 12 months.

Official Title
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Optimal Coronary Flow After PCI for Myocardial Infarction - a Pilot Study

Conditions
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ST-segment Elevation Myocardial Infarction

Intervention / Treatment
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* Drug: alteplase
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Criteria for randomization: 1. IMR measured in culprit vessel > 30 Criteria for IMR measurement: Inclusion Criteria: Oral and signed informed consent Males and females 18 - 85 years of age Diagnosis of ST-elevation myocardial infarction (STEMI) including occlusion of culprit vessel on angiography Onset of continuous symptoms within 12 hours Have undergone PCI of culprit vessel Subjects are willing to comply with scheduled visits and tests and are able and willing to provide informed consent Exclusion Criteria: Previously known ejection fraction <30% Previous PCI in the culprit vessel Chronic total occlusion in major vessel Any history of bleeding diathesis, known coagulopathy, or will refuse blood transfusions Recent history or known platelet count <100.000 cells/mm3 or Hbg < 10 g/dL Known reduced kidney function with estimated glomerular filtration rate (GFR) <30 ml/min/1.73m2. Previous hemorrhagic stroke Ongoing oral anticoagulation treatment Severe asthma requiring daily treatment Any mechanical complication (e.g. ventricular septal defect, papillary muscle rupture, cardiac tamponade) Atrioventricular block grade III Known inability to undergo MRI investigation Permanent pacemaker Pronounced claustrophobia Known intolerance to study drug Known intolerance to adenosine Pregnancy Participation in another investigational drug study Previous randomization in the OPTIMAL-PCI trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alteplase<br>40 patients: 4-5 minutes of infusion of 10 ml of alteplase 2mg/ml in culprit vessel | Drug: alteplase<br> <br> * Other names: Actilyse®;|
| Placebo Comparator: Placebo<br>40 patients: 4-5 minutes of infusion of 10 ml of NaCl in culprit vessel | Drug: Placebo<br> <br> * Other names: NaCl;|
| No Intervention: Observational<br>10 patients with IMR <30 will undergo the same follow-up as the randomised patients | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of myocardial infarct size to area at risk assessed by MRI | MRI performed early (day 2-6) to assess area at risk and late (3 months) to assess infarct size | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of index of microvascular resistance and coronary flow reserve | Difference in invasively measured IMR and CFR before and after drug administration | Immediately after drug administration during invasive index procedure | 
| Degree of microvascular obstruction assessed by MRI | Degree of microvascular obstruction assessed by MRI | 2-6 days | 
| Peak level of Troponin T | Peak level of Troponin T | 12 hours | 
| Level of NtProBNP | Level of NtProBNP | 12 hours | 
| Non invasive CFR | CFR measured with transthoracic echo doppler | 3 months | 
| Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | 3 months | 
| Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | Major adverse cardiac event (myocardial infarction, stroke, heart failure or death) | 12 months | 
| Re-hospitalisation for heart failure | Re-hospitalisation for heart failure | 12 months | 
| Re-hospitalisation for myocardial infarction | Re-hospitalisation for myocardial infarction | 12 months | 
| Cardiovascular death | Cardiovascular death | 12 months | 
| Bleeding according to BARC-criteria | Bleeding events during or after index PCI during index hospitalisation | 7 days | 
| Myocardial hemorrhage at MRI | Myocardial hemorrhage at MRI | 2-6 days | 
| Change in hemoglobin | Change in hemoglobin | 12 hours |