Remote Ischemic Postconditioning in Humans

Study Overview
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Brief Summary
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The aim of this study is to evaluate the phenomenon of remote ischemic post-conditioning in humans. The minor myocardial damage associated with percutaneous revascularization procedures may be attenuated by producing controlled ischemia in the arms immediately after carrying out these procedures (remote ischemic post-conditioning). The justification and design of this clinical trial has been reported: Cardiology. 2011;119(3):164-9.

Detailed Description
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Percutaneous coronary intervention (PCI) has taken on an important role in the treatment of ischemic heart disease in recent years. However, the beneficial effects of revascularization are partly shadowed by post-reperfusion injury, which accounts for up to half the size of the reperfused myocardial infarct. Several drugs and procedures exist that might protect against this phenomenon. One of the most controversial of these strategies, which has shown promising results in experimental animal models, is remote ischemic post-conditioning. This involves inducing ischemia at a site remote from the heart after an ischemic coronary lesion to reduce the resulting myocardial infarct size. The myocardial damage produced by ischemia-reperfusion associated with PCI is a known short- and long-term prognostic factor, and is associated with a greater risk of death, myocardial infarction and revascularization during the follow-up. Our aim is to assess the phenomenon of remote ischemic post-conditioning in patients undergoing PCI, in whom the acute insult on the myocardium is determined by the angioplasty itself. Additionally, we aim to evaluate this phenomenon in a subgroup of diabetic patients, among whom the effectiveness of protective measures against post-reperfusion damage is more questioned. We have designed a randomized, single-blinded interventional study involving 320 patients (40% diabetics) who are to undergo elective PCI. At the end of the angioplasty procedure, the patients assigned to remote ischemic post-conditioning will undergo three 5-minute cycles of ischemia using a blood-pressure cuff at 200 mmHg, placed on the non-dominant arm, interrupted twice for 5 minutes with the cuff deflated. In the control group the procedure will be limited to placing a deflated blood-pressure cuff (pressure: 0 mmHg) for 25 minutes. The infarct size will be analyzed from an enzyme curve of troponin I and CK-MB values 0, 8, 16 and 24 hours after the procedure (primary endpoint). Measurements will also be taken of pH and lactate in the baseline sample (0 hours) and at 8 hours, and ultrasensitive C-reactive protein at 0 and 24 hours as a contrasted marker of inflammation in ischemic heart disease. The follow-up, planned for one year, will seek to determine clinically interesting variables (secondary endpoint), such as readmission due to acute coronary syndrome, heart failure or major arrhythmic events and overall and cardiovascular mortality.

Official Title
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Remote Ischemic Postconditioning. Can it Prevent Myocardial Injury During Percutaneous Coronary Intervention?

Conditions
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Myocardial Reperfusion Injury

Intervention / Treatment
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* Procedure: Remote ischemic postconditioning
* Procedure: Control group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing PCI due to stable angina Patients undergoing PCI due to unstable angina Patients undergoing PCI due NON Q acute myocardial infarction with normal troponin at inclusion moment (less than 1 ng/ml) Exclusion Criteria: Acute myocardial infarction during the previous two weeks Chronic renal failure with baseline creatinine above 3 mg/dL 4. Collateral circulation of the revascularized artery (Rantrop >0) 5. Prior treatment with glibenclamide. 6. Inability to receive follow-up, blood test or lack of informed consent.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remote postcondtioning<br>Patients assigned to remote ischemic postconditioning (randomized controlled trial) | Procedure: Remote ischemic postconditioning<br>* Patients assigned to remote ischemic postconditioning will undergo three 5-minute cycles of ischemia using a blood-pressure cuff at 200 mmHg, placed on the non-dominant arm, interrupted twice for 5 minutes with the cuff deflated<br>|
| Placebo Comparator: Control group<br> | Procedure: Control group<br>* In the control group the procedure will be limited to placing a deflated blood-pressure cuff (pressure: 0 mmHg) for 25 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Increase of Troponin at 24 Hours |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Readmission Due to Acute Coronary Syndrome |  | 12 month | 
| Cardiovascular Mortality |  | 12 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myocardial Reperfusion Injury/mortality, Coronary angioplasty, Reperfusion, Myocardial Reperfusion Injury/prevention & control