Pulmonary Hypertension
Conditions
Keywords
pulmonary hypertension, right ventricular function, ranolazine
Brief summary
This study is looking to see if giving ranolazine to subjects on stable pulmonary hypertension specific therapies but with right ventricular dysfunction (RVEF \<45%) would improve their outcome. This study is accompanied by a baseline comparison of the metabolic profiling/microRNA/iPS cells of subjects with and without right ventricular dysfunction.
Interventions
DRUGRanolazine
Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks.
DRUGPlacebo
Placebo by mouth twice per day for a total of 26 weeks.
Sponsors
The Cardiovascular Medical Research and Education Fund
Brigham and Women's Hospital
University of Maryland
Yale University
Washington University School of Medicine
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Symptomatic pulmonary hypertension based on one of the following criteria: Idiopathic pulmonary arterial hypertension, Familial pulmonary arterial hypertension, pulmonary hypertension associated with connective tissue disease, chronic thromboembolic pulmonary hypertension-nonsurgical/distal vessel disease or patients who are reluctant to go to surgery within a 6-month period and are willing to participate, simple congenital such as repaired atrial septal defect or ventricular septal defect or unrepaired small atrial septal defect or ventricular septal defect with persistent and out of proportion pulmonary arterial hypertension, group 3 patients who have a component of pulmonary arterial hypertension, pulmonary arterial hypertension caused by conditions affect the veins and small vessels of the lungs, sickle cell disease, group 5 pulmonary hypertension such as polycythemia vera, essential thrombocythemia, sarcoidosis, or vasculitis, or metabolic disorder. * WHO functional class II, III, or IV * Mean pulmonary artery pressure \>25 mmHg at rest * Pulmonary capillary wedge pressure or left ventricular end diastolic pressure \< 15 mmHg * Baseline 6-minute walk test distance \> 50 meters * Stable on baseline existing PH specific therapy for 12 weeks with no dosage change within 28 days prior to screening.
Exclusion criteria
* Previous treatment with or prior sensitivity to ranolazine * Any family history of corrected QT interval prolongation, congenital long QT syndrome, or receiving drugs that prolong the corrected QT interval * Parenchymal lung disease showing total lung capacity \< 50% of predicted OR forced expiratory volume at one second/forced vital capacity \< 50% * Portal hypertension associated with liver disease * Left sided heart disease including any of the following: moderate or greater aortic or mitral valve disease, Any left ventricle cardiomyopathy, Left ventricular systolic dysfunction defined as an ejection fraction \< 50%, Symptomatic coronary artery disease * Uncontrolled hypertension * Uncontrolled diabetes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Right Ventricular Ejection Fraction | 6 months | right ventricular ejection fraction by cardiac MRI |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day
Ranolazine: Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day and continue for a total of 26 weeks. | 7 |
| Placebo Placebo by mouth twice per day
Placebo: Placebo by mouth twice per day for a total of 26 weeks. | 6 |
| Observational Patients with pulmonary hypertension who have normal RV function (RVEF \>=45%) will undergo same procedures in the observational arm but will not receive an intervention. | 9 |
| Total | 22 |
Baseline characteristics
| Characteristic | Placebo | Observational | Total | Ranolazine |
|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 6.8 | 53.2 years STANDARD_DEVIATION 17.9 | 54.4 years STANDARD_DEVIATION 15.9 | 53.0 years STANDARD_DEVIATION 19.7 |
| Race and Ethnicity Not Collected | — | — | 0 Participants | — |
| Region of Enrollment United States | 6 participants | 9 participants | 22 participants | 7 participants |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 13 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 | 0 / 9 |
| other Total, other adverse events | 5 / 7 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 1 / 7 | 1 / 6 | 0 / 9 |
Outcome results
Primary
Changes in Right Ventricular Ejection Fraction
right ventricular ejection fraction by cardiac MRI
Time frame: 6 months
Population: Completers
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | Changes in Right Ventricular Ejection Fraction | 5.8 percentage | Standard Error 2 |
| Placebo | Changes in Right Ventricular Ejection Fraction | -4.7 percentage | Standard Error 3.2 |
| Observational | Changes in Right Ventricular Ejection Fraction | 0.49 percentage | Standard Error 3.2 |