Targeting Right Ventricle in Pulmonary Hypertension Gilead

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

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.

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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: University of Maryland; Gilead Sciences; Brigham and Women's Hospital

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, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): January 1, 2018

Study Registration Dates

• First Submitted: July 5, 2016
• First Submitted That Met QC Criteria: July 11, 2016
• First Posted (ESTIMATE): July 12, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

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: 824808

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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