Ischemic Postconditioning in STEMI Patients Treated With Primary PCI

Study Overview
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Brief Summary
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In a prospective, randomized clinical trial the iPOST2 trial will determine whether ischemic postconditioning reduces reperfusion injury and this will translate into improved clinical outcome of heart failure and death for STEMI patients who present with TIMI0-1 undergoing primary PCI

Detailed Description
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Myocardial reperfusion with the use primary percutaneous coronary intervention (PCI) is effective, but restoration of blood flow may itself jeopardize the myocardium, a phenomenon known as reperfusion injury. In ischemic postconditioning (iPOST), repetitive interruptions of blood flow to the injured region applied after initial reperfusion, has been shown favorable with different modalities such as biomarkers, echocardiography and cardiac magnetic resonance. However, the largest trial to date (DANAMI3-iPOST) failed to show clinical favor of iPOST when compared to conventional PCI. Importantly, however, in DANAMI3-iPOST thrombectomy was allowed and this might have impaired postconditioning, since thrombectomy itself creates reperfusion and thus reperfusion damage. Analysis of the fraction of DANAMI3-iPOST patients not undergoing thrombectomy showed a remarkable 45% reduction in death and heart failure in favor of postconditioning. iPOST2 will investigate in a randomized, prospective and adequately powered trial the effect of iPOST without thrombectomy compared to conventional PCI on the development of heart failure and death in STEMI patients.

Official Title
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The Effect of Ischemic Postconditioning in Patients With STEMI Undergoing Primary PCI (DANAMI4-iPOST2)

Conditions
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ST Segment Elevation Myocardial Infarction

Intervention / Treatment
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* Procedure: Ischemic postconditioning
* Procedure: Conventional


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Acute onset of chest pain with < 12 hours duration STEMI as characterized by 2 mm ST elevation in 2 or more V1 through V4 leads or presumed new left bundle branch block with minimum of 1 mm concordant ST elevation or 1 mV ST-segment elevation in the limb lead (II, III and aVF, I, aVL) and V4-V6 or ST depression in 2 or more V1 through V4 leads indicating posterior AMI. TIMI flow 0-1 in infarct related artery Exclusion Criteria: Potential pregnancy Refusal to participate OHCA without subsequent consciousness despite ROSC Thrombectomy considered unavoidable

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective, randomized, placebo controlled
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ischemic postconditioning<br>In addition to state of the art primary PCI in patients with TIMI0-1 ischemic postconditioning with an adequately sized balloon (60 reperfusion/60 seconds re-occlusion, four cycles) will be performed, however thrombectomy will not be allowed | Procedure: Ischemic postconditioning<br>* After 60 seconds of reperfusion, ischemic postconditioning with an adequately sized balloon (60 reperfusion/60 seconds re-occlusion, four cycles) will be performed<br>|
| Placebo Comparator: Conventional<br>State of the art primary PCI in patients with TIMI0-1 will be performed, however thrombectomy will not be allowed | Procedure: Conventional<br>* State of the art primary PCI, however thrombectomy is not allowed<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality or hospitalization for heart failure | Composite endpoint of all cause mortality or hospitalization for heart failure which ever occur first | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | All cause mortality | From date of randomization until the date of first documented death from any cause assessed up to 280 events have been adjudicated or up to 36 months | 
| Percentage of patients hospitalized for heart failure | Any hospitalization for heart failure occurring after the index STEMI | From date of randomization until the date of first documented hospitalization for heart failure assessed up to 280 events have been adjudicated or up to 36 months | 
| Percentage of patients with myocardial infarction | Any myocardial infarction occurring after the index STEMI | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 
| Cardiovascular death | Cardiovascular death | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 
| Percentage of patients with stroke | An acute episode of focal or global neurological dysfunction caused by brain injury | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 
| Percentage of patients with a combination of all-cause mortality, hospitalization for heart failure, new myocardial infarction and stroke/transitory cerebral ischemia | Composite endpoint of all-cause mortality, hospitalization for heart failure, new myocardial infarction and stroke/transitory cerebral ischemia | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 
| Percentage of patients with a combination of hospitalization for heart failure and cardiovascular death | A composite of hospitalization for heart failure and cardiovascular death | From date of randomization until the date of first documented hospitalization for heart failure or date of death from any cause, whichever came first, assessed up to 280 events have been adjudicated or up to 36 months | 
| Danish eq5d5l standard Quality of life | Self assesed quality of life after the Danish eq5d5l standard scale (1 worst score -100 best score) | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary PCI, Ischemic postconditioning, Clinical outcome