Back to results

The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC) (ERIC)

Primary Purpose

Cardiomyopathy

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Ranolazine

About this trial

This is an interventional supportive care trial for Cardiomyopathy focused on measuring The Effects of Ranolazine on CPET Parameters in Ischemic, Cardiomyopathy Patients

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients > 18 years of age will be enrolled in the trial.
Stable patients without hospitalizations, medication changes or cardiac intervention within one month of the study will be enrolled.
Patients must be able to complete the CPET protocol and must have demonstrable ischemia on the initial CPET evaluation.
Patients must have a documented ejection fraction < 40%
a. LV function can be assessed via: i. Echocardiogram ii. MUGA or Nuclear Perfusion Scan iii. Left ventriculogram
Patients must be Ranexa naive and without contraindication for Ranexa therapy.

Exclusion Criteria:

QTc>500 msec on resting EKG
Hepatic Impairment (Child-Pugh class A, B or C)
Have received prior treatment with ranolazine
Treatment with QT prolonging drugs as class 1A (e.g., quinidine), class III (e.g., sotalol, dofetilide) anti-arrhythmics, amiodarone and anti-psychotics (e.g., thioridazine, ziprasidone)
Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole and other azole antifungals, diltiazem, verapamil, macrolide antibiotics, HIV protease inhibitors or consumption of grapefruit juice or grapefruit juice containing products
Have participated in another trial of an investigational device or drug within 30 days of screening
Have end stage renal disease requiring dialysis
Have any chronic illness likely to effect compliance with the protocol
Have second or third degree atrioventricular block in the absence of a functioning ventricular pacemaker
Have uncontrolled clinically significant cardiac arrhythmias, or a history of ventricular fibrillation, torsade de pointes, or other life-threatening ventricular arrhythmias
Uncontrolled HTN defined as BP > /= 160/100 mm Hg

Sites / Locations

Cardiovascular Institute of the South

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Ranolazine Treatment Arm

Arm Description

All patients who meet the criteria of ischemia will receive ranolazine after enrollment. The initial CPET will serve as the control. The second CPET after 30-days of therapy will serve as the therapy arm. CPET parameters will be assessed and compared both on and off therapy.

Outcomes

Primary Outcome Measures

Cardiopulmonary Exercise Test Parameters (CPET).

CPET parameters assessed will include the peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT and peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase.

Secondary Outcome Measures

Full Information

NCT ID

NCT01705509

First Posted

October 10, 2012

Last Updated

February 5, 2020

Sponsor

Cardiovascular Institute of the South Clinical Research Corporation

Collaborators

Gilead Sciences

1. Study Identification

Unique Protocol Identification Number

NCT01705509

Brief Title

The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)

Acronym

ERIC

Official Title

The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Terminated

Why Stopped

Study terminated due to lack of resources.

Study Start Date

September 2012 (Actual)

Primary Completion Date

March 31, 2017 (Actual)

Study Completion Date

March 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Cardiovascular Institute of the South Clinical Research Corporation

Collaborators

Gilead Sciences

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This is a proof of concept trial using ranolazine, a medication, in patients with known Coronary Artery Disease and reduced left ventricular function, EF < 40%. We propose that ranolazine therapy will result in demonstrative improvements in cardiac function that can be objectively assessed using the parameters measured with CPET. We propose that demonstrative improvement in CPET parameters on ranolazine will translate into improved patient outcomes for this patient population.

Detailed Description

Selected patients will undergo a CPET evaluation. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Ischemia will be assessed using: 1) peak VO2: measures the peak transport of O2 to the tissues when O2 extraction from the blood is maximal; 2) the anaerobic threshold (AT): measures the sustainable work capacity in units of VO2; 3) the O2-pulse measurements at the AT peak VO2: estimate stroke volume at those levels of exercise; and 4) the relationship of O2 uptake to work rate (ΔVO2/ΔWR): provides information on the ability of the cardiac output to increase. Patients whoseCPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy. No medication changes or revascularization procedures will occur during the study. If patients require and undergo a medication change or a revascularization procedure, they will be excluded from the study. Patients will be contacted at the completion of week one prior to up titration, then at the end of week two to ensure tolerance and compliance with the 1000mg BID dose. Patients will perform the second CPET study at week four +/- 1 week. The trial medication will be assessed and counted to ensure that patients have taken there allotted pill count for the duration of the study. Patients who are found to be noncompliant of less than 80% will be excluded from the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cardiomyopathy

Keywords

The Effects of Ranolazine on CPET Parameters in Ischemic, Cardiomyopathy Patients

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ranolazine Treatment Arm

Arm Type

Other

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ranolazine

Other Intervention Name(s)

Ranexa

Intervention Description

The intervention will be ranolazine therapy after the initial CPET. The initial CPET will identify patients with underlying ischemia and serve as a baseline study. Patients whose CPET results meet the criteria for ischemia will be started on Ranexa 500mg BID and advanced within one week +/-4 days to 1000mg BID. A second CPET will be performed after 4 weeks +/- 4 days of maximum therapy. CPET results before and after therapy will undergo a statistical comparison. The initial off treatment CPET measurement will serve as the control to assess changes found during therapy.

Primary Outcome Measure Information:

Title

Cardiopulmonary Exercise Test Parameters (CPET).

Description

Time Frame

30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients > 18 years of age will be enrolled in the trial. Stable patients without hospitalizations, medication changes or cardiac intervention within one month of the study will be enrolled. Patients must be able to complete the CPET protocol and must have demonstrable ischemia on the initial CPET evaluation. Patients must have a documented ejection fraction < 40% a. LV function can be assessed via: i. Echocardiogram ii. MUGA or Nuclear Perfusion Scan iii. Left ventriculogram Patients must be Ranexa naive and without contraindication for Ranexa therapy. Exclusion Criteria: QTc>500 msec on resting EKG Hepatic Impairment (Child-Pugh class A, B or C) Have received prior treatment with ranolazine Treatment with QT prolonging drugs as class 1A (e.g., quinidine), class III (e.g., sotalol, dofetilide) anti-arrhythmics, amiodarone and anti-psychotics (e.g., thioridazine, ziprasidone) Treatment with potent or moderately potent CYP3A inhibitors including ketoconazole and other azole antifungals, diltiazem, verapamil, macrolide antibiotics, HIV protease inhibitors or consumption of grapefruit juice or grapefruit juice containing products Have participated in another trial of an investigational device or drug within 30 days of screening Have end stage renal disease requiring dialysis Have any chronic illness likely to effect compliance with the protocol Have second or third degree atrioventricular block in the absence of a functioning ventricular pacemaker Have uncontrolled clinically significant cardiac arrhythmias, or a history of ventricular fibrillation, torsade de pointes, or other life-threatening ventricular arrhythmias Uncontrolled HTN defined as BP > /= 160/100 mm Hg

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Agostino G Ingraldi, M.D.

Organizational Affiliation

Cardiovascular Institute of the South

Official's Role

Principal Investigator

Facility Information:

Facility Name

Cardiovascular Institute of the South

City

Lafayette

State/Province

Louisiana

ZIP/Postal Code

70506

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

20177011

Citation

Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Stafford R, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. 2010 Feb 23;121(7):948-54. doi: 10.1161/CIRCULATIONAHA.109.192666. No abstract available. Erratum In: Circulation. 2010 Mar 30;121(12):e259.

Results Reference

background

PubMed Identifier

9886707

Citation

McMurray JJ, Petrie MC, Murdoch DR, Davie AP. Clinical epidemiology of heart failure: public and private health burden. Eur Heart J. 1998 Dec;19 Suppl P:P9-16.

Results Reference

background

PubMed Identifier

17196454

Citation

Wenger NK, Chaitman B, Vetrovec GW. Gender comparison of efficacy and safety of ranolazine for chronic angina pectoris in four randomized clinical trials. Am J Cardiol. 2007 Jan 1;99(1):11-8. doi: 10.1016/j.amjcard.2006.07.052. Epub 2006 Nov 2.

Results Reference

background

PubMed Identifier

16775092

Citation

Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart. 2006 Jul;92 Suppl 4(Suppl 4):iv6-iv14. doi: 10.1136/hrt.2005.078790.

Results Reference

background

PubMed Identifier

16717165

Citation

Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. No abstract available.

Results Reference

background

PubMed Identifier

12871687

Citation

Belardinelli R, Lacalaprice F, Carle F, Minnucci A, Cianci G, Perna G, D'Eusanio G. Exercise-induced myocardial ischaemia detected by cardiopulmonary exercise testing. Eur Heart J. 2003 Jul;24(14):1304-13. doi: 10.1016/s0195-668x(03)00210-0.

Results Reference

background

PubMed Identifier

16316693

Citation

Contini M, Andreini D, Agostoni P. Cardiopulmonary exercise test evidence of isolated right coronary artery disease. Int J Cardiol. 2006 Nov 10;113(2):281-2. doi: 10.1016/j.ijcard.2005.09.033. Epub 2005 Nov 28.

Results Reference

background

PubMed Identifier

9643272

Citation

Klainman E, Fink G, Lebzelter J, Zafrir N. Assessment of functional results after percutaneous transluminal coronary angioplasty by cardiopulmonary exercise test. Cardiology. 1998 May;89(4):257-62. doi: 10.1159/000006797.

Results Reference

background

Citation

Itoh, H et al. Oxygen uptake abnormalities during exercise in coronary artery disease. In Cardiopulmonary Exercise Testing and Cardiovascular Health. Edited by K. Wasserman, Published by Futura Publishing Company, Armonk NY, 2002.

Results Reference

background

Learn more about this trial

The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)

We'll reach out to this number within 24 hrs