Targeting the Right Ventricle in Pulmonary Hypertension

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Pennsylvania
Sponsor:
Collaborators:
The Cardiovascular Medical Research and Education Fund
Brigham and Women's Hospital
University of Maryland
Yale University
Information provided by (Responsible Party):
Yuchi Han, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01839110
First received: April 17, 2013
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

This study is looking to see if giving ranolazine to subjects on stable pulmonary hypertension specific therapies but with right ventricular dysfunction (RVEF <=40%) 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.


Condition Intervention
Pulmonary Hypertension
Drug: Ranolazine
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Number and percentage of subjects with high risk profile at end of the study [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Number and percentage of subjects with high risk profile at Week 26. Patients with high risk profile are defined as patients with clinical worsening events or lack of clinical improvement at the end of the study.


Secondary Outcome Measures:
  • Glucose and lipid metabolites [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Measure differences in glucose and lipid metabolism in subjects with and without RV dysfunction at baseline.

  • Changes from baseline in glucose and lipid metabolism [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measure fold changes in glucose and lipid metabolism in subjects with persistent right ventricle dysfunction after treatment with and without ranolazine.


Estimated Enrollment: 90
Study Start Date: July 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Ranexa
Placebo Comparator: Placebo
Placebo by mouth twice per day
Drug: Placebo
Placebo by mouth twice per day for a total of 26 weeks.
No Intervention: Observational
Patients with pulmonary hypertension who have near normal RV function (RVEF >40%) will undergo same procedures in the observational arm but will not receive an intervention.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, simple congenital such as repaired atrial or ventricular septal defect or unrepaired small atrial or ventricular septal defect with persistent and out of proportion pulmonary arterial hypertension
  • 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
  • Untreated severe obstructive sleep apnea
  • 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
  • Moderate to severe chronic renal disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01839110

Contacts
Contact: Yuchi Han, MD 215-662-2855 yuchi.han@uphs.upenn.edu
Contact: Amanda Baer, MB, MBA 215-746-3423 baer2@mail.med.upenn.edu

Locations
United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Myung Park, MD       mpark@medicine.umaryland.edu   
Contact: Lioubov Poliakova       lpoliako@medicine.umaryland.edu   
Principal Investigator: Myung Park, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Aaron Waxman, MD, PhD       abwaxman@partners.org   
Contact: Laurie Lawler, RN       llawler@partners.org   
Principal Investigator: Aaron Waxman, MD, PhD         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Yuchi Han, MD       yuchi.han@uphs.upenn.edu   
Contact: Amanda Baer, MB, MBA       baer2@mail.med.upenn.edu   
Principal Investigator: Yuchi Han, MD         
Sponsors and Collaborators
University of Pennsylvania
The Cardiovascular Medical Research and Education Fund
Brigham and Women's Hospital
University of Maryland
Yale University
Investigators
Principal Investigator: Yuchi Han, MD University of Pennsylvania
  More Information

No publications provided

Responsible Party: Yuchi Han, Assistant Professor of Medicine, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01839110     History of Changes
Other Study ID Numbers: 817785
Study First Received: April 17, 2013
Last Updated: February 20, 2014
Health Authority: United States: Data and Safety Monitoring Board
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Pennsylvania:
pulmonary hypertension
right ventricular function
ranolazine

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Ventricular Dysfunction, Right
Ventricular Dysfunction
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Heart Diseases
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014