Remote Ischemic Conditioning With Local Ischemic Postconditioning in High-Risk ST-elevation Myocardial Infarction

Study Overview
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Brief Summary
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The RIP-HIGH trial is a two-arm randomized controlled trial aiming to compare the impact of combined remote ischemic conditioning (RIP) and local ischemic postconditioning (PostC) vs. standard of care on clinical outcome in high-risk ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Detailed Description
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Coronary reperfusion by percutaneous coronary intervention is mandatory to salvage ischemic myocardium and to reduce definite infarct size. However, reperfusion itself also causes irreversible myocardial damage - a phenomenon described as reperfusion injury. Reduction of ischemic and reperfusion injury by ischemic conditioning has been identified as a potential target to reduce myocardial damage. Remote ischemic conditioning and local ischemic postconditioning might be in particular of clinical benefit in higher risk STEMI patients with Killip class ≥2, where mortality rates are high. The Remote Ischemic Conditioning with Local Ischemic Postconditioning in High-Risk ST-elevation myocardial infarction patients (RIP-HIGH) trial is a two-arm randomized controlled trial aiming to compare the impact of combined remote ischemic conditioning and local ischemic postconditioning vs. standard of care on clinical outcome in high-risk ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention.

Official Title
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Randomized Comparison of Combined Remote Ischemic Conditioning and Local Postconditioning Compared to Standard Treatment in High-risk ST-elevation Myocardial Infarction Patients

Conditions
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ST Elevation Myocardial Infarction

Intervention / Treatment
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* Procedure: RIC + PostC + Standard PCI
* Procedure: Standard PCI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute chest pain lasting <12 h ST-elevation at the J-point in two contiguous leads of ≥2 mm in men ≥40 years, ≥2.5 mm in men <40 years and ≥1.5 mm in women (regardless of age) in V2-V3 and/or ≥1 mm in all other leads (52). New or presumed new left bundle branch block or right bundle branch block. Killip class ≥II on hospital admission or requirement of diuretics because of clinical congestion. Written informed consent. Exclusion Criteria: Killip class I on hospital admission. Prior fibrinolysis. Conditions precluding use of RIC (i.e. paresis of the upper limb, presence of an arteriovenous shunt). Pregnancy. Age <18 years. Severe co-morbidity with a life expectancy <6 months. Participation in another trial.

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: patients will be randomized to one of the two groups in a 1:1 ratio stratified by center
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RIC + PostC in addition to standard treatment<br>RIC by arm ischemia initiated on hospital admission plus local PostC by re-inflating the angioplasty balloon after re-opening the infarct-related artery in addition to standard treatment. | Procedure: RIC + PostC + Standard PCI<br>* RIC by arm ischemia initiated on hospital admission plus local PostC by re-inflating the angioplasty balloon after re-opening the infarct-related artery<br>|
| Active Comparator: Standard treatment<br> | Procedure: Standard PCI<br>* Standard PCI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of all-cause mortality or hospitalization for heart failure (HF) within 12 months after randomization. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality at 12 months |  | 12 months | 
| Hospitalization for heart failure at 12 months |  | 12 months | 
| Composite of all-cause mortality, HF hospitalization and survived out-of-hospital cardiac arrest at 12 months |  | 12 months | 
| Cardiovascular mortality at 12 months. |  | 12 months | 
| Enzymatic infarct size defined as high-sensitivity cardiac troponin T (hs-TnT) levels 72 h after randomization |  | day 3 | 
| Change in N-terminal pro B-type natriuretic peptide (NT-proBNP) levels during admission and 72 h after randomization |  | day 0, day 3 | 
| Thrombolysis in myocardial infarction (TIMI)-flow grade of the culprit vessel post PCI |  | day 0 | 
| Proportion of patients showing complete (≥70%) resolution of ST-segment elevation 60 minutes after reperfusion |  | day 0 | 
| CMR-derived infarct size. |  | day 2-5 | 
| CMR-derived myocardial salvage index |  | day 2-5 | 
| Extent of CMR-derived late microvascular obstruction on day 2-5 after randomization |  | day 2-5 | 
| all-cause mortality, HF hospitalization and survived out-of-hospital cardiac arrest assessed at 5 years via telephone contact. |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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remote ischemic conditioning, local ischemic postconditioning, percutaneous coronary intervention