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 therapies but with right ventricular dysfunction (RVEF \<45%) will improve their health by improving right ventricular (RV) function.
Interventions
DRUGRanolazine
Ranolazine 500mg by mouth twice per day and after two weeks increases 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
Brigham and Women's Hospital
University of Maryland
Gilead Sciences
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 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 * Vasculitis * Metabolic disorder * World Health Organization 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 * Pulmonary vascular resistance \> 3 mmHg/L/min * Right ventricle ejection fraction \< 45% * 6-minute walk test distance \> 50 meters
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 chronic 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 systemic hypertension * Implantable cardioverter-defibrillator, Pacemaker, hazardous metallic implants or any other contraindication to MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage) | 26 weeks | Change in right ventricle ejection fraction as assessed by MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in 6min-walk-test Distance | 6 months | 6-minute walk test |
| Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | 6 months | NT-proBNP measured at 6-months compared to baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ranolazine Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day
Ranolazine: Ranolazine 500mg by mouth twice per day and after two weeks increases to 1000mg by mouth twice per day and continue for a total of 26 weeks. | 14 |
| Placebo Placebo by mouth twice per day
Placebo: Placebo by mouth twice per day for a total of 26 weeks | 8 |
| Total | 22 |
Baseline characteristics
| Characteristic | Placebo | Total | Ranolazine |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 20 Participants | 13 Participants |
| Age, Continuous | 53.6 years STANDARD_DEVIATION 14.1 | 54.8 years STANDARD_DEVIATION 16 | 55.4 years STANDARD_DEVIATION 16.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 15 Participants | 9 Participants |
| Region of Enrollment United States | 8 participants | 22 participants | 14 participants |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 1 / 8 |
| other Total, other adverse events | 11 / 14 | 4 / 8 |
| serious Total, serious adverse events | 3 / 14 | 2 / 8 |
Outcome results
Primary
Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage)
Change in right ventricle ejection fraction as assessed by MRI
Time frame: 26 weeks
Population: participants who completed follow up study at 6 months.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage) | 7.56 percentage | Standard Error 1.72 |
| Placebo | Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage) | -3.99 percentage | Standard Error 2.23 |
Secondary
Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
NT-proBNP measured at 6-months compared to baseline
Time frame: 6 months
Population: completers
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | -119.72 pg/mL | Standard Error 276.42 |
| Placebo | Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | -287.75 pg/mL | Standard Error 353.81 |
Secondary
Percent Change in 6min-walk-test Distance
6-minute walk test
Time frame: 6 months
Population: complete and recorded data
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ranolazine | Percent Change in 6min-walk-test Distance | -0.09 percentage of distance walked | Standard Error 0.095 |
| Placebo | Percent Change in 6min-walk-test Distance | -0.06 percentage of distance walked | Standard Error 0.125 |