Hypertrophic Cardiomyopathy
Conditions
Keywords
chest pain, dyspnea
Brief summary
The purpose of RHYME is to evaluate the safety and efficacy of ranolazine in Hypertrophic Cardiomypathy patients with chest pain or dyspnea despite treatment with standard medical therapy. This is a small, pilot, open-label (non-randomized) study of an approved drug for the treatment of angina in a novel patient population (adult patient population with hypertrophic cardiomyopathy).
Interventions
DRUGRanolazine
Sponsors
Gilead Sciences
Duke University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Left Ventricle wall thickness \>/= 15mm in the absence of other condition causing hypertrophy * Baseline Angina/Shortness of Breath Frequency of \> 2 episodes per week * Willing to provide informed consent
Exclusion criteria
* Severe stenotic valvular disease * Severe valvular regurgitation except mitral regurgitation due to systolic anterior motion * Significant (\>60% stenosis) coronary artery disease * Acute coronary syndrome within 30 days * Severe heart failure defined as LV systolic dysfunction with Ejection Fraction \<40% or NYHA class 4 symptoms * Severe renal impairment (glomerular filtration rate, \<30 mL/min/1.73 m2) * Moderate-severe hepatic impairment (Child-Pugh classes B and C) * Hospitalization for cardiac reason within 3 months of enrollment * Anticipated changes to treatment of HCM within study period, including medications, device implantation, or septal reduction therapies * Concomitant use of ketoconazole, macrolide antibiotics, and HIV protease inhibitors * Active myocarditis, pericarditis, or restrictive cardiomyopathy * Non-cardiac terminal illness with expected survival less than 6 months * Women who are of childbearing potential * Inability to perform or adhere to study protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| QT Interval | 60 Days | — |
| Number of Adverse Events Considered Probably or Possibly Related to Study Drug | 60 Days | Number of events that are considered probably or possibly related to study drug. |
| Drug Tolerability | 60 days | Total number of patients that tolerated 1,000mg BID dose and 500 mg BID dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Number of Episodes of Angina Per Week | Baseline and 60 Days post treatment | Efficacy of ranolazine in HCM patients with respect to improvements in angina frequency (number of episodes of angina per week). |
| Seattle Angina Questionnaire (SAQ) | 60 Days post treatment | The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | 60 days post treatement | Kansas City Cardiomyopathy Questionnaire (KCCQ) (scores range from 0 to 100 with higher scores representative of a higher quality of life; clinically important changes are considered \> 10 points and \>5 points, respectively, as previously established |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine, 500 mg for 60 days | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Ranolazine |
|---|---|
| Age, Continuous | 63.2 years STANDARD_DEVIATION 9 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical summary | 58.8 units on a scale STANDARD_DEVIATION 20.9 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall summary | 51.2 units on a scale STANDARD_DEVIATION 22.3 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Physical limitation | 61.7 units on a scale STANDARD_DEVIATION 20.6 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of life | 39.4 units on a scale STANDARD_DEVIATION 26.6 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Self-efficacy | 78.4 units on a scale STANDARD_DEVIATION 21.7 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Social limitation | 46.0 units on a scale STANDARD_DEVIATION 31.5 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom burden | 55.3 units on a scale STANDARD_DEVIATION 29.4 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom frequency | 56.4 units on a scale STANDARD_DEVIATION 20.6 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Symptom stability | 43.2 units on a scale STANDARD_DEVIATION 16.2 |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) Total symptom score | 55.9 units on a scale STANDARD_DEVIATION 24.2 |
| Seattle Angina Questionnaire Anginal frequency | 65.5 units on a scale STANDARD_DEVIATION 13.4 |
| Seattle Angina Questionnaire Anginal stability | 45.5 units on a scale STANDARD_DEVIATION 27 |
| Seattle Angina Questionnaire Physical limitation | 49.6 units on a scale STANDARD_DEVIATION 18.7 |
| Seattle Angina Questionnaire Quality of life | 40.9 units on a scale STANDARD_DEVIATION 24.6 |
| Seattle Angina Questionnaire Treatment satisfaction | 85.2 units on a scale STANDARD_DEVIATION 12.6 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Drug Tolerability
Total number of patients that tolerated 1,000mg BID dose and 500 mg BID dose
Time frame: 60 days
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ranolazine | Drug Tolerability | 1000 mg BID | 9 participants |
| Ranolazine | Drug Tolerability | 500 mg BID | 4 participants |
Primary
Number of Adverse Events Considered Probably or Possibly Related to Study Drug
Number of events that are considered probably or possibly related to study drug.
Time frame: 60 Days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ranolazine | Number of Adverse Events Considered Probably or Possibly Related to Study Drug | 10 adverse event |
Primary
QT Interval
Time frame: 60 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | QT Interval | 462.8 msec | Standard Deviation 27.4 |
Secondary
Improvement in Number of Episodes of Angina Per Week
Efficacy of ranolazine in HCM patients with respect to improvements in angina frequency (number of episodes of angina per week).
Time frame: Baseline and 60 Days post treatment
Population: episodes of angina per week was not collected
Secondary
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Kansas City Cardiomyopathy Questionnaire (KCCQ) (scores range from 0 to 100 with higher scores representative of a higher quality of life; clinically important changes are considered \> 10 points and \>5 points, respectively, as previously established
Time frame: 60 days post treatement
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Physical limitation | 72 units on a scale | Standard Deviation 20.6 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Symptom stability | 72.7 units on a scale | Standard Deviation 26.1 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Symptom frequency | 72.2 units on a scale | Standard Deviation 20 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Symptom burden | 75 units on a scale | Standard Deviation 24.2 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Total symptom score | 73.6 units on a scale | Standard Deviation 21.3 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Self-efficacy | 85.2 units on a scale | Standard Deviation 14.6 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Quality of life | 65.2 units on a scale | Standard Deviation 25.8 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Social limitation | 66.1 units on a scale | Standard Deviation 31.2 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Overall summary | 69.8 units on a scale | Standard Deviation 23.5 |
| Ranolazine | Kansas City Cardiomyopathy Questionnaire (KCCQ) | Clinical summary | 74 units on a scale | Standard Deviation 20.5 |
Secondary
Seattle Angina Questionnaire (SAQ)
The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life.
Time frame: 60 Days post treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ranolazine | Seattle Angina Questionnaire (SAQ) | Physical limitation | 61.4 units on a scale | Standard Deviation 18 |
| Ranolazine | Seattle Angina Questionnaire (SAQ) | Anginal stability | 90.0 units on a scale | Standard Deviation 21.1 |
| Ranolazine | Seattle Angina Questionnaire (SAQ) | Anginal frequency | 86.0 units on a scale | Standard Deviation 12.7 |
| Ranolazine | Seattle Angina Questionnaire (SAQ) | Treatment satisfaction | 90.6 units on a scale | Standard Deviation 11.5 |
| Ranolazine | Seattle Angina Questionnaire (SAQ) | Quality of life | 70.8 units on a scale | Standard Deviation 11.3 |