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Coronary Artery DiseasePhase 2/3RIMINI-PilotNCT01797484

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

A Phase 2/3 study testing Ranolazine in people with Coronary Artery Disease and Acute Myocardial Ischemia, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ranolazine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteGermany
Study dates
Aug 2013to Jun 2015
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site
  • University Heart Center Hamburg Eppendorf

    Hamburg, 20246

Other trials in Germany

About this study

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.

Read more

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.

Read the 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.

Being tested
Ranolazine
Keywords
ischemia, myocardium, Ranolazine, dyskinesia, speckle tracking echocardiography
Medical subject headings
Coronary Artery Disease, Ischemia, Dyskinesias

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanolazineDrug

    Also called Ranexa

    Improvement of myocardial microcirculation

Study groups in NCT01797484
Study groupRoleWhat they receive
RanolazineActive comparatorRanolazine 500mg bid orally 7 days Ranolazine 750mg bid orally 35 days
Receives: Drug: Ranolazine
No additional medicationNo interventionNo additional medication - control group

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 42 days after first dose of Ranolazine

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01797484
Sponsor's protocol ID
UHZ-KARD-01-2013
Acronym
RIMINI-Pilot
Status last verified
Jan 2018
First submitted
20 Feb 2013
Last updated
12 Jan 2018
Data monitoring committee
Yes
Individual data sharing
Yes

Publications

  • 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.

    PubMed 17456819
  • 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.

    PubMed 19909934
  • 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.

    PubMed 20840192
  • 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.

    PubMed 19004841
  • 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.

    PubMed 17569677
  • 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.

    PubMed 21270073
  • 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.

    PubMed 16990383
  • 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.

    PubMed 20717762
  • 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.

    PubMed 20362924
  • 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.

    PubMed 29938533

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ranolazine in people with Coronary Artery Disease and Acute Myocardial Ischemia, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Left Ventricular Global Strain Rate (time frame: 42 days after first dose of Ranolazine). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01797484, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2018.

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