Targeting Right Ventricle in Pulmonary Hypertension Gilead

Phase 4

Completed

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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Ranolazine	Ranolazine	Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day
Placebo	Placebo	Placebo by mouth twice per day

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Locations (3): University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
University of Maryland
🇺🇸
Baltimore, Maryland, United States