Targeting Right Ventricle in Pulmonary Hypertension Gilead

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multi-center Study to Assess the Effect of Ranolazine in Subjects With Pulmonary Hypertension and Right Ventricular Dysfunction Using Cardiovascular MRI

Conditions
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Pulmonary Hypertension

Intervention / Treatment
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* Drug: Ranolazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine<br>Ranolazine 500mg by mouth twice per day and after two weeks increase to 1000mg by mouth twice per day | Drug: Ranolazine<br>* 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.<br>* Other names: Ranexa;|
| Placebo Comparator: Placebo<br>Placebo by mouth twice per day | Drug: Placebo<br>* Placebo by mouth twice per day for a total of 26 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline Right Ventricular Ejection Fraction (the Unit is Percentage) | Change in right ventricle ejection fraction as assessed by MRI | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in 6min-walk-test Distance | 6-minute walk test | 6 months | 
| Change in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) | NT-proBNP measured at 6-months compared to baseline | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, right ventricular function, ranolazine