Targeting the Right Ventricle in Pulmonary Hypertension

University of Pennsylvania

Status and phase: Completed; Phase 4

Conditions: Pulmonary Hypertension

Treatments: Drug: Placebo; Drug: Ranolazine

Study type: Interventional

Funder types: Other

Identifiers

NCT01839110

817785

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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22 participants in 3 patient groups, including a placebo group

Ranolazine

Active Comparator group

Description:

Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day

Treatment:

Drug: Ranolazine

Placebo

Placebo Comparator group

Description:

Placebo by mouth twice per day

Treatment:

Drug: Placebo

Observational

No Intervention group

Description:

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.