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

This study is currently recruiting participants.
Verified January 2014 by Cardiovascular Institute of the South Clinical Research Corporation
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Cardiovascular Institute of the South Clinical Research Corporation
ClinicalTrials.gov Identifier:
NCT01705509
First received: October 10, 2012
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention
Cardiomyopathy
Drug: Ranolazine

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: The Effects of Ranolazine on CPET Parameters in Ischemic Cardiomyopathy Patients (ERIC)

Resource links provided by NLM:


Further study details as provided by Cardiovascular Institute of the South Clinical Research Corporation:

Primary Outcome Measures:
  • Cardiopulmonary Exercise Test Parameters (CPET). [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 50
Study Start Date: September 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Ranolazine Treatment Arm
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.
Drug: Ranolazine
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.
Other Name: Ranexa

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01705509

Contacts
Contact: Agostino G Ingraldi, MD 337-988-1585 agostino.ingraldi@cardio.com
Contact: Cindy Landry, LPN 337-291-6956 cindy.landry@cardio.com

Locations
United States, Louisiana
Cardiovascular Institute of the South Recruiting
Lafayette, Louisiana, United States, 70506
Contact: Cindy Landry, LPN    337-291-6956    cindy.landry@cardio.com   
Principal Investigator: Agostino G Ingraldi, M.D.         
Sponsors and Collaborators
Cardiovascular Institute of the South Clinical Research Corporation
Gilead Sciences
Investigators
Principal Investigator: Agostino G Ingraldi, M.D. Cardiovascular Institute of the South
  More Information

Publications:
Responsible Party: Cardiovascular Institute of the South Clinical Research Corporation
ClinicalTrials.gov Identifier: NCT01705509     History of Changes
Other Study ID Numbers: 20121250
Study First Received: October 10, 2012
Last Updated: January 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Cardiovascular Institute of the South Clinical Research Corporation:
The Effects of Ranolazine on CPET Parameters in Ischemic
Cardiomyopathy Patients

Additional relevant MeSH terms:
Cardiomyopathies
Heart Diseases
Cardiovascular Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014