Reduction of Ischemic Myocardium With Ranolazine-Treatment in Patients With Acute Myocardial Ischemia

NCT01797484 | Completed Phase 2 Results DMC

• 1 other identifier: UHZ-KARD-01-2013
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Artery Disease; Acute Myocardial Ischemia

Keywords

ischemia; myocardium; Ranolazine; dyskinesia; speckle tracking echocardiography

Outcome Measures

Primary Outcomes (1)

• Left Ventricular Global Strain Rate

  Relativ acceleration or deceleration (1/s) of left ventricular myocardial sections compared to direct opposite section. The more positive the value, the more simultaneously the movements, the more hemodynamically better.

  42 days after first dose of Ranolazine

Study Arms (2)

Ranolazine

ACTIVE COMPARATOR

Ranolazine 500mg bid orally 7 days Ranolazine 750mg bid orally 35 days

Drug: Ranolazine

No additional medication

NO INTERVENTION

No additional medication - control group

Interventions

Ranolazine DRUG

Improvement of myocardial microcirculation

Also known as: Ranexa

Ranolazine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Heart Center Hamburg Eppendorf

Hamburg, 20246, Germany

Location

Related Publications (10)

• Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S, Wolff AA, Skene A, McCabe CH, Braunwald E; MERLIN-TIMI 36 Trial Investigators. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA. 2007 Apr 25;297(16):1775-83. doi: 10.1001/jama.297.16.1775.

  PMID: 17456819 BACKGROUND

• Venkataraman R, Belardinelli L, Blackburn B, Heo J, Iskandrian AE. A study of the effects of ranolazine using automated quantitative analysis of serial myocardial perfusion images. JACC Cardiovasc Imaging. 2009 Nov;2(11):1301-9. doi: 10.1016/j.jcmg.2009.09.006.

  PMID: 19909934 BACKGROUND

• El-Kadri M, Sharaf-Dabbagh H, Ramsdale D. Role of antiischemic agents in the management of non-ST elevation acute coronary syndrome (NSTE-ACS). Cardiovasc Ther. 2012 Feb;30(1):e16-22. doi: 10.1111/j.1755-5922.2010.00225.x. Epub 2010 Sep 15.

  PMID: 20840192 BACKGROUND

• Van de Werf F, Bax J, Betriu A, Blomstrom-Lundqvist C, Crea F, Falk V, Filippatos G, Fox K, Huber K, Kastrati A, Rosengren A, Steg PG, Tubaro M, Verheugt F, Weidinger F, Weis M; ESC Committee for Practice Guidelines (CPG). Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J. 2008 Dec;29(23):2909-45. doi: 10.1093/eurheartj/ehn416. Epub 2008 Nov 12. No abstract available.

  PMID: 19004841 BACKGROUND

• Task Force for Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of European Society of Cardiology; Bassand JP, Hamm CW, Ardissino D, Boersma E, Budaj A, Fernandez-Aviles F, Fox KA, Hasdai D, Ohman EM, Wallentin L, Wijns W. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2007 Jul;28(13):1598-660. doi: 10.1093/eurheartj/ehm161. Epub 2007 Jun 14. No abstract available.

  PMID: 17569677 BACKGROUND

• Andersen GO, Knudsen EC, Aukrust P, Yndestad A, Oie E, Muller C, Seljeflot I, Ueland T. Elevated serum osteoprotegerin levels measured early after acute ST-elevation myocardial infarction predict final infarct size. Heart. 2011 Mar;97(6):460-5. doi: 10.1136/hrt.2010.206714. Epub 2011 Jan 26.

  PMID: 21270073 BACKGROUND

• Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grogaard HK, Bjornerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006 Sep 21;355(12):1199-209. doi: 10.1056/NEJMoa055706.

  PMID: 16990383 BACKGROUND

• Miller TD, Gibbons RJ. Measuring myocardium at risk in acute myocardial infarction--a continuing challenge. J Nucl Cardiol. 2010 Oct;17(5):778-80. doi: 10.1007/s12350-010-9278-3. No abstract available.

  PMID: 20717762 BACKGROUND

• Geyer H, Caracciolo G, Abe H, Wilansky S, Carerj S, Gentile F, Nesser HJ, Khandheria B, Narula J, Sengupta PP. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr. 2010 Apr;23(4):351-69; quiz 453-5. doi: 10.1016/j.echo.2010.02.015.

  PMID: 20362924 BACKGROUND

• Schwemer TF, Radziwolek L, Deutscher N, Diermann N, Sehner S, Blankenberg S, Friedrich FW. Effect of Ranolazine on Ischemic Myocardium IN Patients With Acute Cardiac Ischemia (RIMINI-Trial): A Randomized Controlled Pilot Trial. J Cardiovasc Pharmacol Ther. 2019 Jan;24(1):62-69. doi: 10.1177/1074248418784290. Epub 2018 Jun 24.

  PMID: 29938533 DERIVED

Related Links

• University Heart Center Hamburg Eppendorf

MeSH Terms

Conditions

Coronary Artery Disease; Ischemia; Dyskinesias

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Tjark F. Schwemer
• Organization: University Heart Centre Hamburg Eppendorf

t.schwemer@uke.de

+49 40 7410

Study Officials

• Stefan Blankenberg, Prof. Dr.

  Director of University Heart Center Hamburg Eppendorf

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. med.

Study Record Dates

• First Submitted: February 20, 2013
• First Posted: February 22, 2013
• Study Start: August 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: January 12, 2018
• Results First Posted: January 12, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)