Ranolazine Loading to Prevent PCI-induced Myocardial Injury

Study Overview
=================
Brief Summary
-----------------
It has previously been shown that pretreatment with ranolazine 1,000 mg twice daily for 7 days can significantly reduce procedural myocardial injury in elective percutaneous coronary intervention (PCI). The investigators tested the hypothesis that twice overnight high-dose ranolazine loading before PCI can reduce the peri-procedural myocardial ischemic damage similarly to long-term pre-treatment with standard doses.

Detailed Description
-----------------
Background Ranolazine is a novel antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia thus limiting ischemic injury. It has previously been shown that pretreatment with ranolazine 1,000 mg twice daily for 7 days can significantly reduce procedural myocardial injury in elective percutaneous coronary intervention. It remains unknown, however, which of these two therapeutic approaches is more effective after PCI. Purpose The primary objective of this study is to test the hypothesis that twice overnight high-dose ranolazine loading before PCI can reduce the peri-procedural myocardial ischemic damage similarly to long-term pre-treatment with standard doses.

Official Title
-----------------
TWice overnIght High-dose ranoLazIne Pretreatment for preventinG Myocardial iscHemic Damage in Patients With Stable Angina Undergoing percuTaneous Coronary Intervention

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Drug: Ranolazine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Angiographically-proven coronary artery disease Class I indication to elective percutaneous coronary intervention Stable conditions No recent acute coronary syndromes Normal baseline values of markers of myocardial damage (creatine kinase, creatine kinase-MB, myoglobin, and troponin I) Able to understand and willing to sign the informed consent form Exclusion Criteria: • Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours before
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine<br>Administration of two preprocedural doses of Ranolazine 12 hours apart (1,000 mg the night before PCI and 1,000 mg prior to PCI) | Drug: Ranolazine<br>* os, 1,000 mg twice 12 hours apart prior to PCI<br>* Other names: Ranexa TM, Gilead, USA;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* os, two doses 12 hours apart prior to PCI<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of PCI-induced myocardial infarction | Occurrence of peri-procedural myocardial infarction (i.e. creatine kinase-MB>3 times the upper reference limit) | Up to 48 hours after PCI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of post-PCI peak values of markers of myocardial damage | Changes after percutaneous coronary intervention in absolute values of creatine kinase, creatine kinase-MB, myoglobin, and troponin I | Baseline and 48 hours after PCI | 
| Rate of 30-day MACE | 30-day incidence of major adverse cardiac events (MACE-death, myocardial infarction, target vessel revascularization) | Up to 30 days after PCI | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ranolazine, periprocedural myocardial infarction