Cardiomyopathy
Conditions
Keywords
The Effects of Ranolazine on CPET Parameters in Ischemic, Cardiomyopathy Patients
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.
Interventions
DRUGRanolazine
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.
Sponsors
Gilead Sciences
Cardiovascular Institute of the South Clinical Research Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiopulmonary Exercise Test Parameters (CPET). | 30 days | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CPET Control / CPET With Ranexa Enrolled patients will undergo a CPET evaluation. Beta Blockers will be held day prior to and day of 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 B ID 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. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| CPET w/ Ranexa | Screen Failure | 2 |
| Inclusion CPET | Screen Failure | 5 |
| Inclusion CPET | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | CPET Control / CPET With Ranexa |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 68 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 4 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
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.
Time frame: 30 days
Population: Number of Participants who Reached CPET Milestones
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control | Cardiopulmonary Exercise Test Parameters (CPET). | Failed Initial CPET | 5 Participants |
| Control | Cardiopulmonary Exercise Test Parameters (CPET). | Withdrew Prior to CPET | 2 Participants |
| Control | Cardiopulmonary Exercise Test Parameters (CPET). | Screenfailed due to Ranolazine Intolerance | 2 Participants |
| Control | Cardiopulmonary Exercise Test Parameters (CPET). | Completed | 5 Participants |