Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention (PCI)

Study Overview
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Brief Summary
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Background: Experimental studies suggest that remote limb ischaemic postconditioning (RemPostCon) can reduce infarct size in pigs. Initial clinical applications support the beneficial role of RemPostCon in preserving endothelial function during upper limb ischemia in healthy volunteers and in patients with stable coronary artery disease. Aim of the study: To evaluate the feasibility, safety and efficacy of RemPostCon in the setting of STEMI and primary PCI (pPCI) and to investigate potential circulating mediators of its effects. Patients and methods: Patients who undergo pPCI for anterior STEMI within 6 hours since the onset of symptoms are randomly assigned to receive either RemPostCon + pPCI or pPCI alone in a single-blind fashion. All patients receive therapy according to the current international guidelines. Three cycles of ischemia-reperfusion are provided to the lower limb inflating a cuff to 200 mmHg. Each cycle consists of 5' of ischaemia, followed by 5' of reperfusion. RemPostCon is started at the time of angioplasty in the infarct related artery. Primary endpoint is the area under the curve (AUC) of creatinine kinase - MB (CK - MB). Cardiac magnetic resonance (CMR) is performed early before discharge and 4 months after the event, if there are no contraindications.

Official Title
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Pilot Study to Test Feasibility, Safety, Molecular Mediators and Preliminary Efficacy of Remote Myocardial Postconditioning Provided With Extrinsic Cuff Compression of Lower Limb During Primary PCI

Conditions
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Myocardial Reperfusion Injury, Myocardial Ischemia, Myocardial Infarction

Intervention / Treatment
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* Procedure: Remote Postconditioning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 yrs AND Age =< 80 yrs STEMI definition Pain to door time < 6 hrs Killip class 1 - 2 - 3 Initial TIMI flow 0 - 1 in the anterior descending artery Signed informed consent Exclusion Criteria: Pregnancy Cardiogenic shock Initial TIMI flow 2 - 3 in the anterior descending artery History of prior MI in the past 6 months History of prior CABG History of peripheral vascular disease III - IV grade History of abdominal Aortic Aneurysm > 5 cm Severe coronaropathy that could condition further revascularization before the end of the study Other relevant medical or surgical conditions that can influence prognosis at 4 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: RemotePostConditioning<br>Patients will receive pPCI and treatments according to guidelines for STEMI PLUS extrinsic cuff compression to the lower limb for 5 ' followed by 5' reperfusion for three cycles (30' in total) starting with myocardial reperfusion | Procedure: Remote Postconditioning<br>* Lower limb compression using a cuff inflated to 200 mmHg for 5 ' followed by 5' of reperfusion fo three times during 30'<br>|
| Sham Comparator: Controls<br>pPCI and treatments according to guidelines for STEMI | Procedure: Remote Postconditioning<br>* Lower limb compression using a cuff inflated to 200 mmHg for 5 ' followed by 5' of reperfusion fo three times during 30'<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of CK - MB release |  | baseline to 72h since admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve of CK release |  | baselinte to 72h since admission | 
| TIMI Frame Count |  | 30 minutes after first balloon inflation in infarct-related artery | 
| Time to balloon |  | during pPCI | 
| Ejection Fraction MRI |  | before discharge and after 4 months | 
| Myocardial Blush grading |  | 30 minutes after first balloon inflation | 
| ST segment resolution |  | 6h after balloon | 
| Troponin I peak |  | 72h since admission | 
| Mortality rate |  | 4 months since admission | 
| artero-venous differences in pO2, pCO2, pH, HCo3 |  | baseline and 30 minutes after first balloon inflation | 
| Major adverse cardiac events |  | 4 months since admission | 
| artero-venous quantitative and qualitative differences in endothelial progenitors cells (subgroups) |  | within 24 h since admission | 
| artero-venous Differences of Cytokines |  | within 24h since admission | 
| Edema Volume T2 sequences MRI |  | before discharge | 
| Delay enhancement volume MRI |  | before discharge and after 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Remote Postconditioning, Myocardial reperfusion Injury, Myocardial Infarction, Primary PCI