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
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Acute Myocardial Ischemia
Drug: Ranolazine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Reduction of Ischemic Myocardium With Ranolazine-Treatment in Patients With Acute Myocardial Ischemia

Resource links provided by NLM:


Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:
  • Area of ischemic myocardium/cm² (longitudinal strain, radial/circumferential strain) [ Time Frame: 42 days after first dose of Ranolazine ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ranolazine
Ranolazine 500mg bid orally 7 days Ranolazine 750mg bid orally 35 days
Drug: Ranolazine
Improvement of myocardial microcirculation
Other Name: Ranexa
No Intervention: No additional medication
No additional medication - control group

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01797484

Contacts
Contact: Tjark F Schwemer, MD +49407410 ext 56800 t.schwemer@uke.de
Contact: Britta Goldmann, MD +49407410 ext 56800 goldmann@uke.de

Locations
Germany
University Heart Center Hamburg Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Tjark F Schwemer, MD    +49407410 ext 56800    t.schwemer@uke.de   
Contact: Britta Goldmann, MD    +49407410 ext 56800    goldmann@uke.de   
Sub-Investigator: Tjark F Schwemer, MD         
Sub-Investigator: Britta Goldmann, MD         
Sub-Investigator: Philipp Peitsmeyer         
Sub-Investigator: Felix Friedrich, MD         
Sponsors and Collaborators
Universitätsklinikum Hamburg-Eppendorf
Investigators
Principal Investigator: Stefan Blankenberg, Prof. Dr. Director of University Heart Center Hamburg Eppendorf
  More Information

Additional Information:
Publications:

Responsible Party: Tjark Frederik Schwemer, Dr. med., Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier: NCT01797484     History of Changes
Other Study ID Numbers: UHZ-KARD-01-2013
Study First Received: February 20, 2013
Last Updated: July 8, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:
ischemia
myocardium
Ranolazine
dyskinesia
speckle tracking echocardiography

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Ischemia
Acute Coronary Syndrome
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Angina Pectoris
Chest Pain
Pain
Signs and Symptoms
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014