Targeting the Right Ventricle in Pulmonary Hypertension

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 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.

Official Title
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A Randomized, Double-blind, Placebo Controlled, Multi-center Study to Assess the Effect of Ranolazine on Outcomes in Subjects With Pulmonary Hypertension and Right Ventricular Dysfunction Accompanied by a Comparative Study of Cellular Metabolism in Subjects With Pulmonary Hypertension With and Without Right Ventricular Dysfunction

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 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

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 at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day | Drug: Ranolazine<br>* 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.<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>|
| No Intervention: Observational<br>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. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Right Ventricular Ejection Fraction | right ventricular ejection fraction by cardiac MRI | 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