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Reduction of Ischemic Myocardium With Ranolazine-Treatment in Patients With Acute Myocardial Ischemia (RIMINI-Pilot)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Universitätsklinikum Hamburg-Eppendorf
Sponsor:
Information provided by (Responsible Party):
Tjark Frederik Schwemer, Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01797484
First received: February 20, 2013
Last updated: July 8, 2013
Last verified: July 2013

February 20, 2013
July 8, 2013
July 2013
June 2014   (final data collection date for primary outcome measure)
Area of ischemic myocardium/cm² (longitudinal strain, radial/circumferential strain) [ Time Frame: 42 days after first dose of Ranolazine ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01797484 on ClinicalTrials.gov Archive Site
  • Incidence of cardiac complications (i.e. ventricular tachycardia, re-infarction, rehospitalisation for revascularization) [ Time Frame: 42 days after first dose of Ranolazine ] [ Designated as safety issue: No ]
  • Level of cardiac markers (NT-pro-BNP, Troponin, CK, Copeptin) [ Time Frame: Before and 42 days after first dose of Ranolazine ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Reduction of Ischemic Myocardium With Ranolazine-Treatment in Patients With Acute Myocardial Ischemia
Reduction of Ischemic Myocardium With Ranolazine-Treatment in Patients With Acute Myocardial Ischemia

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
  • Coronary Artery Disease
  • Acute Myocardial Ischemia
Drug: Ranolazine
Improvement of myocardial microcirculation
Other Name: Ranexa
  • Active Comparator: Ranolazine
    Ranolazine 500mg bid orally 7 days Ranolazine 750mg bid orally 35 days
    Intervention: Drug: Ranolazine
  • No Intervention: No additional medication
    No additional medication - control group

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
September 2014
June 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Proof of acute cardiac ischemia by elevated serum Troponin T-hs levels > 14 pg/nl
  • Proof of myocardial dyskinesia with functional echocardiography ("speckle tracking")
  • Stable angina pectoris >/= CCS II in patient history
  • Stabilized (i.e. normalized vital parameters) patients after coronary angioplasty or angiography
  • Coronary angioplasty or angiography not older than 24 hours
  • Written informed consent
  • Established standard therapy for coronary artery disease (i.e. Beta-Blocker, ACE-Inhibitor or AT1-Inhibitor, ASS, Clopidogrel, Statins)

Exclusion Criteria:

  • Patients younger than 18 years of age
  • Acute cardio-pulmonary decompensation
  • Middle and high grade liver insufficiency (Child-Pugh Score B and C)
  • High grade renal insufficiency (Creatinine-Clearance < 30 ml/min)
  • Concomitant treatment with potent inhibitors of CYP3A4
  • Concomitant administration of class Ia (e.g. quinidine) or class III (e.g. dofetilide, sotalol) antiarrhythmics, except for amiodarone
  • Concomitant administration of > 20 mg simvastatin/day
  • Patients with heart failure classification NYHA III and NYHA IV
  • Homeless patients and drug-addicted patients
  • Pregnant and/or breast-feeding women
  • Treatment with Ranolazine prior to enrolment in RIMINI-Trial
  • Allergy against Ranolazine
Both
18 Years and older
No
Contact: Tjark F Schwemer, MD +49407410 ext 56800 t.schwemer@uke.de
Contact: Britta Goldmann, MD +49407410 ext 56800 goldmann@uke.de
Germany
 
NCT01797484
UHZ-KARD-01-2013
Yes
Tjark Frederik Schwemer, Universitätsklinikum Hamburg-Eppendorf
Universitätsklinikum Hamburg-Eppendorf
Not Provided
Principal Investigator: Stefan Blankenberg, Prof. Dr. Director of University Heart Center Hamburg Eppendorf
Universitätsklinikum Hamburg-Eppendorf
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP