Targeting the Right Ventricle in Pulmonary Hypertension

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension
• Intervention / Treatment: Drug: Ranolazine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo by mouth twice per day	Drug: Placebo; Placebo by mouth twice per day for a total of 26 weeks.
ACTIVE_COMPARATOR: Ranolazine; Ranolazine at 500mg by mouth twice per day and after two weeks will increase to 1000mg by mouth twice per day	Drug: Ranolazine; 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.; Other Names: Ranexa
NO_INTERVENTION: Observational; 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?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Right Ventricular Ejection Fraction	right ventricular ejection fraction by cardiac MRI	6 months

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Washington University School of Medicine; Yale University; University of Maryland; Brigham and Women's Hospital; The Cardiovascular Medical Research and Education Fund

Publications and helpful links

General Publications

• Han Y, Forfia PR, Vaidya A, Mazurek JA, Park MH, Ramani G, Chan SY, Waxman AB. Rationale and design of the ranolazine PH-RV study: a multicentred randomised and placebo-controlled study of ranolazine to improve RV function in patients with non-group 2 pulmonary hypertension. Open Heart. 2018 Feb 23;5(1):e000736. doi: 10.1136/openhrt-2017-000736. eCollection 2018.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2013
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: April 17, 2013
• First Submitted That Met QC Criteria: April 21, 2013
• First Posted (ESTIMATE): April 24, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 5, 2019
• Last Update Submitted That Met QC Criteria: January 14, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: pulmonary hypertension; right ventricular function; ranolazine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: 817785

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD available upon request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No