Trial Outcomes & Findings for The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction (NCT NCT01505179)
NCT ID: NCT01505179
Last Updated: 2020-01-18
Results Overview
Exercise capacity in terms of exercise duration (time in seconds) as described for the baseline value, is repeated at 6 weeks.
COMPLETED
NA
10 participants
6 weeks
2020-01-18
Participant Flow
Between 12/2011 and 3/2013, the UCSD Echo database of \>4500 patients (pts) and their electronic medical records were screened. Of the 1200 pts with left ventricular (LV) ejection fraction (EF) \>45%, only 60 pts met all inclusion criteria. Informed consent was obtained from 10 pts who were subsequently randomized and completed study protocols.
Pts meeting all inclusion criteria were most often excluded due to the presence of atrial fibrillation, being unable to perform the minimum exercise effort required, or walked \> 550 meters on the 6MW test. The remaining pts were excluded for acute heart failure (HF) decompensation, baseline QTc \> 500 ms or participation in another clinical trial .
Participant milestones
| Measure |
Ranolazine Group
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
4
|
|
Overall Study
COMPLETED
|
6
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Ranolazine Group
n=6 Participants
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 Participants
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
Total
n=10 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
79.5 years
n=6 Participants
|
75.5 years
n=4 Participants
|
77.9 years
n=10 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=6 Participants
|
4 Participants
n=4 Participants
|
7 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=6 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=10 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Exercise Duration
|
608.6 seconds
STANDARD_DEVIATION 253.1 • n=6 Participants
|
328.8 seconds
STANDARD_DEVIATION 128.8 • n=4 Participants
|
496.7 seconds
STANDARD_DEVIATION 206.5 • n=10 Participants
|
|
Peak Oxygen Uptake (VO2)
|
15.9 mL O2/kg/min
STANDARD_DEVIATION 2.3 • n=6 Participants
|
15.7 mL O2/kg/min
STANDARD_DEVIATION 2.1 • n=4 Participants
|
15.8 mL O2/kg/min
STANDARD_DEVIATION 2.3 • n=10 Participants
|
|
6MW test distance
|
382.5 meters
STANDARD_DEVIATION 88.2 • n=6 Participants
|
298.2 meters
STANDARD_DEVIATION 76.3 • n=4 Participants
|
348.8 meters
STANDARD_DEVIATION 83.4 • n=10 Participants
|
|
BNP
|
111.7 pg/mL
STANDARD_DEVIATION 86.4 • n=6 Participants
|
184.8 pg/mL
STANDARD_DEVIATION 87.1 • n=4 Participants
|
140.9 pg/mL
STANDARD_DEVIATION 86.6 • n=10 Participants
|
|
Quality of Life (QOL) Score
|
36.7 units on a scale
STANDARD_DEVIATION 20.3 • n=6 Participants
|
48.8 units on a scale
STANDARD_DEVIATION 36.3 • n=4 Participants
|
41.5 units on a scale
STANDARD_DEVIATION 26.7 • n=10 Participants
|
|
Septal E/e' Doppler velocity ratio
|
16.2 unitless
STANDARD_DEVIATION 3.2 • n=6 Participants
|
17.0 unitless
STANDARD_DEVIATION 5.8 • n=4 Participants
|
16.5 unitless
STANDARD_DEVIATION 4.2 • n=10 Participants
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Entire study population
Exercise capacity in terms of exercise duration (time in seconds) as described for the baseline value, is repeated at 6 weeks.
Outcome measures
| Measure |
Ranolazine Group
n=6 Participants
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 Participants
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
Change in Exercise Capacity at 6 Weeks
|
659.9 seconds
Standard Deviation 284.5
|
300.5 seconds
Standard Deviation 92.4
|
PRIMARY outcome
Timeframe: 6 weeksPopulation: Entire study population
Oxygen consumption (VO2) as described at baseline is remeasured after 6 weeks of drug vs placebo.
Outcome measures
| Measure |
Ranolazine Group
n=6 Participants
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 Participants
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
Change in Oxygen Consumption (VO2) at 6 Weeks
|
17.8 ml/kg/min
Standard Deviation 3.4
|
13.5 ml/kg/min
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: The analysis population is comprised of the 10 patients who were eligible and consented for participation in the trial. Six patients were assigned to the Ranolazine group and four to the placebo group, randomization was by chance.
The Minnesota Living with Heart Failure (HF) Questionnaire was re-administered at the 6 week time point. The total quality of life (QOL) scores were compared to the baseline score. The well-validated Minnesota Living with Heart Failure questionnaire is self-administered, has 21 questions and takes 5-10 minutes to complete. The test measures perceived health-related QOL. Each question is scored from 0 to 5 on the Likert scale, where 0 is 'none', and 5 is 'very much'. QOL scores range from 0 to 105; a lower score represents a better quality of life. After an intervention, a decrease in score reflects an improvement in QOL. A minimally important difference in the total score is 5 points.
Outcome measures
| Measure |
Ranolazine Group
n=6 Participants
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 Participants
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
Change in Quality of Life (QOL) Score
|
38.2 units on a scale
Standard Deviation 24.7
|
50.9 units on a scale
Standard Deviation 65.5
|
SECONDARY outcome
Timeframe: 6 weeksPopulation: Entire Study Population
Doppler echo allows non-invasive evaluation of diastolic cardiac function. The mitral inflow velocity (E) correlates with LV filling pressure, but is influenced by myocardial relaxation time (RT) and filling pressure. The early diastolic septal mitral annular tissue velocity (e') varies with RT alone. The unitless ratio of the E to e' velocities (E/e') is considered a reliable surrogate of LV filling pressure. Prediction of normal diastolic filling pressure is most reliable when E/e' is \< 8; and of abnormal filling pressure when E/e' is \> 15. The percent change is reported.
Outcome measures
| Measure |
Ranolazine Group
n=6 Participants
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 Participants
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
Change in Doppler Echocardiographic Parameters, Septal E/e' Ratio (E/e')
|
-15 percent change
Standard Deviation 35
|
-1 percent change
Standard Deviation 9.4
|
Adverse Events
Ranolazine Group
Placebo Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Ranolazine Group
n=6 participants at risk
Patients with be given 500 mg Ranolazine by mouth twice a day for three days, and then the dose will be increased to 1000 mg by mouth twice daily thereafter. (patients who concurrently take moderate CYP3A inhibitors including diltiazem, verapamil, aprepitant, erythromycin, and fluconazole will continue to 500 mg by mouth twice a day for the entire dosing period)
|
Placebo Group
n=4 participants at risk
Patients will be given Placebo matching the appearance of Ranolazine as 1 tab twice a day for 3 days, then increasing to 2 tabs twice a day thereafter (patients who concurrently take moderate CYP3A inhibitors, will be given 1 tab twice daily for the entire dosing period)
|
|---|---|---|
|
General disorders
Minor adverse event
|
16.7%
1/6 • Number of events 1 • Duration of trial, 6 weeks.
The definition of adverse events and serious adverse events are not different from those found in clinicaltrials.gov definitions. The study sponsor was provided with quarterly reports regarding any/all defined AE's and SAE's for patients in our study. The sponsor provided us with safety letters and reports of AE/SAE's regarding ranolazine in all active clinical trials (globally).
|
25.0%
1/4 • Number of events 1 • Duration of trial, 6 weeks.
The definition of adverse events and serious adverse events are not different from those found in clinicaltrials.gov definitions. The study sponsor was provided with quarterly reports regarding any/all defined AE's and SAE's for patients in our study. The sponsor provided us with safety letters and reports of AE/SAE's regarding ranolazine in all active clinical trials (globally).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place