Ranolazine Mediated PVC Reduction in Ischemic Heart Disease

NCT02360397 | Completed Phase 2 Results

• 1 other identifier: IN-US-259-1341
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether ranolazine has beneficial effects on cardiac ischemia through reduction of premature ventricular contraction burden.

Conditions

Ventricular Premature Complexes; Myocardial Ischemia

Outcome Measures

Primary Outcomes (2)

• The Effect of Ranolazine on the PVC Burden Over 30 Days

  The change in percentage of PVC burden after taking Ranolazine 1000mg twice daily for 30 days

  Baseline (7 day) Holter compared to day 30 (7 day) Holter

• The Effect of Ranolazine on Cardiac Ischemia

  The effect of ranolazine on cardiac ischemia as measured by change in millimeters of ST segment deviation on ECG monitoring at Baseline and after 30 days of Ranolazine therapy (day 30).

  Baseline and day 30

Secondary Outcomes (2)

• Score on Seattle Angina Questionnaire at Baseline and at Day 30

  Baseline and day 30

• Number of Non-sustained Ventricular Tachycardia and Sustained Ventricular Arrhythmia Episodes on Holter Monitoring

  Baseline and Day 30

Study Arms (1)

Ranolazine

EXPERIMENTAL

Ranolazine 1000 mg tablet twice daily for 30 days

Drug: ranolazine

Interventions

ranolazine DRUG

Ranolazine 1000 mg tablet twice daily for 30 days

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:

• Males and females aged 18 years and older
• Have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
• History of ischemic heart disease (prior bypass or coronary stenting, documentation on cardiac catheterization, nuclear SPECT imaging, cardiac MR, stress echocardiography, or exercise stress testing). Subjects are not required to have chronic angina to be enrolled in the study
• Elevated PVC burden (1%) on prior Holter/event monitor in previous 12 months or evidence for PVC(s) on baseline ECG within prior 12 months.
• Sexually active females of childbearing potential must agree to utilize effective methods of contraception during heterosexual intercourse throughout the treatment period and for 14 days following discontinuation of the study medication

You may not qualify if:

• Hospitalization for hyperthyroidism, pericarditis, myocarditis, or pulmonary embolism within 4 weeks prior to screening
• Implantation of ICD or permanent pacemaker within 1 month of screening
• New York Heart Association (NYHA) Class III and IV heart failure or NYHA Class II heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic within 4 weeks prior to Screening.
• Myocardial infarction, unstable angina, or coronary artery bypass graft (CABG) surgery within three months prior to Screening or percutaneous coronary intervention (PCI) within 4 weeks prior to Screening
• Clinically significant valvular disease in the opinion of the Investigator
• Stroke within 1 months prior to Screening
• History of serious ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation) within 4 weeks prior to Screening
• Family history of long QT syndrome
• QTc ≥ 500 msec (Bazett) at Screening ECG if in sinus rhythm (SR). If in AF, evidence of QTc ≥ 500 msec (Bazett) within 4 weeks prior to Screening
• Prior heart transplant
• Cardiac ablation within 3 months prior to Screening, or planned ablation during the course of the study
• Need for concomitant treatment during the trial, with drugs or products that are strong inhibitors of CYP3A, or inducers of CYP3A. Such medications should be discontinued 5-half- lives prior to the Run-in period
• Use of grapefruit juice or Seville orange juice during the study
• Use of drugs that prolong the QT interval
• Previous use of ranolazine within 2 months prior to screening

Sponsors & Collaborators

• Kent Hospital, Rhode Island: lead
• Gilead Sciences: collaborator

Study Sites (1)

Kent Hospital

Warwick, Rhode Island, 02886, United States

Location

Related Publications (14)

• Scirica BM, Braunwald E, Belardinelli L, Hedgepeth CM, Spinar J, Wang W, Qin J, Karwatowska-Prokopczuk E, Verheugt FW, Morrow DA. Relationship between nonsustained ventricular tachycardia after non-ST-elevation acute coronary syndrome and sudden cardiac death: observations from the metabolic efficiency with ranolazine for less ischemia in non-ST-elevation acute coronary syndrome-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2010 Aug 3;122(5):455-62. doi: 10.1161/CIRCULATIONAHA.110.937136. Epub 2010 Jul 19.

  PMID: 20644019 BACKGROUND

• Scirica BM, Morrow DA, Budaj A, Dalby AJ, Mohanavelu S, Qin J, Aroesty J, Hedgepeth CM, Stone PH, Braunwald E. Ischemia detected on continuous electrocardiography after acute coronary syndrome: observations from the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction 36) trial. J Am Coll Cardiol. 2009 Apr 21;53(16):1411-21. doi: 10.1016/j.jacc.2008.12.053.

  PMID: 19371824 BACKGROUND

• Kumar K, Nearing BD, Carvas M, Nascimento BC, Acar M, Belardinelli L, Verrier RL. Ranolazine exerts potent effects on atrial electrical properties and abbreviates atrial fibrillation duration in the intact porcine heart. J Cardiovasc Electrophysiol. 2009 Jul;20(7):796-802. doi: 10.1111/j.1540-8167.2009.01437.x. Epub 2009 Feb 27.

  PMID: 19298570 BACKGROUND

• Scirica BM, Morrow DA, Hod H, Murphy SA, Belardinelli L, Hedgepeth CM, Molhoek P, Verheugt FW, Gersh BJ, McCabe CH, Braunwald E. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007 Oct 9;116(15):1647-52. doi: 10.1161/CIRCULATIONAHA.107.724880. Epub 2007 Sep 5.

  PMID: 17804441 BACKGROUND

• Kunadian B, Sutton AG, Vijayalakshmi K, Thornley AR, Gray JC, Grech ED, Hall JA, Harcombe AA, Wright RA, Smith RH, Murphy JJ, Shyam-Sundar A, Stewart MJ, Davies A, Linker NJ, de Belder MA. Early invasive versus conservative treatment in patients with failed fibrinolysis--no late survival benefit: the final analysis of the Middlesbrough Early Revascularisation to Limit Infarction (MERLIN) randomized trial. Am Heart J. 2007 May;153(5):763-71. doi: 10.1016/j.ahj.2007.02.021.

  PMID: 17452151 BACKGROUND

• Ephrem G, Levine M, Friedmann P, Schweitzer P. The prognostic significance of frequency and morphology of premature ventricular complexes during ambulatory holter monitoring. Ann Noninvasive Electrocardiol. 2013 Mar;18(2):118-25. doi: 10.1111/anec.12010. Epub 2012 Nov 22.

  PMID: 23530481 BACKGROUND

• Yokokawa M, Good E, Crawford T, Chugh A, Pelosi F Jr, Latchamsetty R, Jongnarangsin K, Armstrong W, Ghanbari H, Oral H, Morady F, Bogun F. Recovery from left ventricular dysfunction after ablation of frequent premature ventricular complexes. Heart Rhythm. 2013 Feb;10(2):172-5. doi: 10.1016/j.hrthm.2012.10.011. Epub 2012 Oct 23.

  PMID: 23099051 BACKGROUND

• Ban JE, Park HC, Park JS, Nagamoto Y, Choi JI, Lim HE, Park SW, Kim YH. Electrocardiographic and electrophysiological characteristics of premature ventricular complexes associated with left ventricular dysfunction in patients without structural heart disease. Europace. 2013 May;15(5):735-41. doi: 10.1093/europace/eus371. Epub 2012 Nov 29.

  PMID: 23194696 BACKGROUND

• Lee V, Hemingway H, Harb R, Crake T, Lambiase P. The prognostic significance of premature ventricular complexes in adults without clinically apparent heart disease: a meta-analysis and systematic review. Heart. 2012 Sep;98(17):1290-8. doi: 10.1136/heartjnl-2012-302005. Epub 2012 Jul 10.

  PMID: 22781425 BACKGROUND

• Baman TS, Lange DC, Ilg KJ, Gupta SK, Liu TY, Alguire C, Armstrong W, Good E, Chugh A, Jongnarangsin K, Pelosi F Jr, Crawford T, Ebinger M, Oral H, Morady F, Bogun F. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm. 2010 Jul;7(7):865-9. doi: 10.1016/j.hrthm.2010.03.036. Epub 2010 Mar 27.

  PMID: 20348027 BACKGROUND

• Le VV, Mitiku T, Hadley D, Myers J, Froelicher VF. Rest premature ventricular contractions on routine ECG and prognosis in heart failure patients. Ann Noninvasive Electrocardiol. 2010 Jan;15(1):56-62. doi: 10.1111/j.1542-474X.2009.00340.x.

  PMID: 20146783 BACKGROUND

• John RM, Tedrow UB, Koplan BA, Albert CM, Epstein LM, Sweeney MO, Miller AL, Michaud GF, Stevenson WG. Ventricular arrhythmias and sudden cardiac death. Lancet. 2012 Oct 27;380(9852):1520-9. doi: 10.1016/S0140-6736(12)61413-5.

  PMID: 23101719 BACKGROUND

• Mountantonakis SE, Hutchinson MD. Indications for implantable cardioverter-defibrillator placement in ischemic cardiomyopathy and after myocardial infarction. Curr Heart Fail Rep. 2011 Dec;8(4):252-9. doi: 10.1007/s11897-011-0069-1.

  PMID: 21769565 BACKGROUND

• Hickey KT, Reiffel J, Sciacca RR, Whang W, Biviano A, Baumeister M, Castillo C, Talathothi J, Garan H. Correlating perceived arrhythmia symptoms and quality of life in an older population with heart failure: a prospective, single centre, urban clinic study. J Clin Nurs. 2013 Feb;22(3-4):434-44. doi: 10.1111/j.1365-2702.2012.04307.x.

  PMID: 23301579 BACKGROUND

MeSH Terms

Conditions

Ventricular Premature Complexes; Myocardial Ischemia

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Cardiac Complexes, Premature; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Chester M. Hedgepeth, MD, PhD
• Organization: Brigham and Women's Cardiovascular Associates at Kent Hospital

chedgepeth@kentri.org

(401) 737-7010

Study Officials

• Chester M Hedgepeth, MD, PhD

  Brigham and Women's Cardiovascular Associates at Care New England

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chester Hedgepeth, MD, PhD

Study Record Dates

• First Submitted: January 20, 2015
• First Posted: February 10, 2015
• Study Start: December 1, 2014
• Primary Completion: December 31, 2017
• Study Completion: February 23, 2018
• Last Updated: January 29, 2020
• Results First Posted: January 29, 2020

Record last verified: 2020-01

Locations

US (1)