Clinical trial NCT01797484
Conditions: Coronary Artery Disease Acute Myocardial Ischemia
Keywords: ischemia myocardium Ranolazine dyskinesia speckle tracking echocardiography
Sponsor: Universitätsklinikum Hamburg-Eppendorf
Start date: 2013-08-01; Completion date: 2015-06-01
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The aim of the RIMINI-Trial is to examine the effect of Ranolazine on ischemic myocardium in acute myocardial ischemia.

A pilot-trial by Venkatamaran et al. recently demonstrated, that the area of ischemic myocardium in patients with stable coronary artery disease can be reduced by Ranolazine-treatment2. This effect was shown by significantly reduced areas of atypical or dysfunctional myocardium in SPECT-examinations.

The dimension of myocardial damage (i.e. area of ischemic myocardium) is directly related to the rate of complications (i.e. left-ventricular pump failure, malignant arrhythmia) and the grade of Rehabilitation to daily life (i.e. persistent reduced left-ventricular ejection fraction).

In patients with stable angina pectoris, Ranolazine is used with beneficial results1. Ranolazine improves diastolic blood flow and therefore microcirculation in the myocardium by reducing diastolic tension (via inhibiting late Na+-Influx and consecutive Ca2+-Overload).

Recently published data2 showed that treatment with Ranolazine significantly reduces the ischemic area in chronic damaged myocardium. This is due the effect of improved microcirculation in hibernating myocardium.

Early administration of Ranolazine and improvement of microcirculation in patients with acute damaged myocardium (i.e. directly after acute ischemia) should lead to a recruitment and re-uptake of cardiac activity of hibernating myocardium.

For the RIMINI-Trial patients are given Ranolazine on top of the guideline-based treatment to reduce the area of acute ischemic myocardium.

Patients with unstable angina pectoris and proof of acute cardiac ischemia, proof of myocardial dyskinesia and angina pectoris in the patient history will receive unaltered guideline-based therapy for acute cardiac ischemia5,6. All necessary procedures will be performed to stabilize patients to a hemodynamically compensated state and patients are then transferred to receive cardiac catheterization (angiography and angioplasty if necessary).

After patients are stabilized Ranolazine will be given additionally to guideline based medication.

The measurement of the ischemic myocardial area will be done via three functional echocardiographies with speckle tracking technique10.

A statistical evaluation of ischemic myocardial area before and after treatment with Ranolazine/Placebo will be done after conclusion of the RIMINI-Trial to show the effect of Ranolazine in acute myocardial ischemia.

Detailed description:
The aim of the RIMINI-Trial is to examine the effect of Ranolazine on ischemic myocardium in acute myocardial ischemia.

A pilot-trial by Venkatamaran et al. recently demonstrated, that the area of ischemic myocardium in patients with stable coronary artery disease can be reduced by Ranolazine-treatment2. This effect was shown by significantly reduced areas of atypical or dysfunctional myocardium in SPECT-examinations.

The dimension of myocardial damage (i.e. area of ischemic myocardium) is directly related to:

1. Rate of complications (i.e. left-ventricular pump failure, malignant arrhythmia)
2. Grade of Rehabilitation to daily life (i.e. persistent reduced left-ventricular ejection fraction)

Early angioplasty and coronary medication are key factors for preventing complications and ensuring sufficient rehabilitation. This is done to reduce the ischemic area as best as possible.

In patients with stable angina pectoris, Ranolazine is used with beneficial results1. Ranolazine improves diastolic blood flow and therefore microcirculation in the myocardium by reducing diastolic tension (via inhibiting late Na+-Influx and consecutive Ca2+-Overload).

Recently published data2 showed that treatment with Ranolazine significantly reduces the ischemic area in chronic damaged myocardium. This is due the effect of improved microcirculation in hibernating myocardium.

Early administration of Ranolazine and improvement of microcirculation in patients with acute damaged myocardium (i.e. directly after acute ischemia) should lead to a recruitment and re-uptake of cardiac activity of hibernating myocardium.

For the RIMINI-Trial patients are given Ranolazine on top of the guideline-based treatment to reduce the area of acute ischemic myocardium.

Patients with unstable angina pectoris and proof of acute cardiac ischemia (Serum levels of Troponin-T-hs \>14 pg/ml), proof of myocardial dyskinesia and angina pectoris \>/=CCS II (Canadian Cardiovascular Society Classification of Angina Pectoris) in the patient history will receive unaltered guideline-based therapy for acute cardiac ischemia5,6. All necessary procedures will be performed to stabilize patients to a hemodynamically compensated state (normalized levels of blood pressure, heart rate, absent malignant arrhythmia, dyspnoea and angina-like symptoms), and patients are then transferred to receive cardiac catheterization (angiography and angioplasty if necessary).

After patients are stabilized (i.e. via angioplasty, medical treatment) Ranolazine will be given additionally to guideline-based medication (Beta-Blocker, ACE-Inhibitor or AT1-Inhibitor, ASS, Clopidogrel, Statins).

The measurement of the ischemic myocardial area will be done via three functional echocardiographies with speckle tracking technique10 (speckle -tracking echocardiography, SPE):

1. The first speckle tracking for screening and will be done directly with patients presenting in the emergency room.
2. After stabilization and coronary angiography or -plasty and before the first dose of Ranolazine is given, the second speckle tracking will be done for baseline.
3. After 42 days of Ranolazine-treatment the third and final speckle tracking echocardiography will be done.

A statistical evaluation of ischemic myocardial area before and after treatment with Ranolazine/Placebo will be done after conclusion of the RIMINI-Trial to show the effect of Ranolazine in acute myocardial ischemia.

For controlling and comparing the effect, the RIMINI-Trial will be single-blinded and compared to a group of patients not treated with Ranolazine. Participants will be randomized to the treatment-group or the no-treatment-group using a computer based randomization-method.

Arms: arm 1: Ranolazine 500mg bid orally 7 days Ranolazine 750mg bid orally 35 days arm 2: No additional medication - control group
Interventions: intervention 1: Ranolazine
Intervention descriptions: intervention 1: Improvement of myocardial microcirculation

Protocol documents: