We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Ranolazine and Pulmonary Hypertension

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01174173
Recruitment Status : Completed
First Posted : August 3, 2010
Results First Posted : April 23, 2015
Last Update Posted : May 11, 2018
Gilead Sciences
Information provided by (Responsible Party):
Sanjiv Shah, Northwestern University

Brief Summary:
The purpose of the study is to determine if the medication, ranolazine (study drug), can help improve blood flow to your heart, increase your exercise capacity and improve your quality of life (QOL). For this study, you will be asked to perform several tests in order to determine if your heart function, exercise capacity, chest pain and QOL have improved after 3 months of treatment with ranolazine. Ranolazine is approved by the U.S. Food and Drug Administration (FDA) for the treatment of angina.

Condition or disease Intervention/treatment Phase
Angina Pulmonary Arterial Hypertension Drug: Ranolazine Phase 3

Detailed Description:

This study is looking to enroll patients with pulmonary hypertension (PH). PH is abnormally high blood pressure in the arteries of the lungs. It makes the right side of the heart need to work harder than normal and is usually caused by a narrowing of the small arteries of the lung. This narrowing makes it harder for the right side of the heart to circulate the blood to the lungs. Over time, the right side of the heart may become enlarged and symptoms (such as angina [chest pain] shortness of breath, fatigue, edema) begin to appear.

Ranolazine is a safe, well-tolerated, and FDA-approved medication for the treatment of chronic stable angina. Ranolazine may potentially improve blood flow to the right ventricle (RV), thereby relieving angina while simultaneously improving RV performance and contractility. This latter effect may increase stroke volume and cardiac output which could translate into benefits in exercise capacity and improved quality of life.

The purpose of this single center, non-randomized, prospective pilot study is to investigate the effects of 3 months treatment with ranolazine on pulmonary artery hemodynamics, exercise capacity and quality of life in patients with PAH and symptoms of angina or angina equivalent.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effects of Ranolazine in Patients With Angina Due to Right Ventricular Ischemia in Pulmonary Arterial Hypertension
Study Start Date : June 2010
Actual Primary Completion Date : January 2014
Actual Study Completion Date : October 2014

Arm Intervention/treatment
Experimental: Ranolazine
1000 mg PO BID
Drug: Ranolazine
ranolazine 1000 mg PO BID for 3 months
Other Name: Ranexa

Primary Outcome Measures :
  1. Improve Angina Symptoms [ Time Frame: 3 months ]
    Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment

  2. 6-Minute Walk Test [ Time Frame: 3 Months ]
    Improve Exercise Capacity measured by 6-Minute Walk Test

  3. Improve Quality of Life [ Time Frame: 3 Months ]
    The Kansas City Cardiomyopathy Questionnaire is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. The scores are averaged and transformed to a range of 0-100, in which higher scores reflect better health status and was performed at the conclusion of the study.

Secondary Outcome Measures :
  1. RV Perfusion on Cardiac MRI [ Time Frame: 3 months ]
    The majority of patients did not undergo cardiac MRI because it was difficult for the patients to tolerate the imaging study. Therefore, we were not able to assess change in RV perfusion.

  2. Absolute RV Longitudinal Strain [ Time Frame: 3 months ]
    Change in absolute right ventricular (RV) longitudinal strain as assessed by exercise stress echocardiography with speckle-tracking echocardiography at baseline and conclusion of the study. An increase in exercise-induced change in RV longitudinal strain between baseline to conclusion of the study is indicative of improved RV function. If absolute RV longitudinal strain increases with exercise, that is a sign that the RV is working well. If absolute RV longitudinal strain decreases with exercise, that is a sign that the RV is not working well. Therefore, between baseline and conclusion of the study, if exercise-induced change in RV strain increases that means that the RV is working better at the conclusion of the study.

  3. Right Ventricular Hemodynamics [ Time Frame: 3 months ]
    Mean pulmonary artery pressure was assessed invasively by right heart catheterization at the conclusion of the study to estimate right ventricular hemodynamics.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. World Health Organization (WHO) Group 1 PAH, defined as a pulmonary hypertension with mean pulmonary artery pressure > 25 mmHg, pulmonary capillary wedge pressure < 15 mmHg, and pulmonary vascular resistance > 3 Wood units.
  2. Right ventricular dysfunction, defined as RV fractional area change < 32% or RV tricuspid annular plane systolic excursion (TAPSE) < 15 mm.
  3. Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric pain, exertional nausea).
  4. New York Heart Association functional class II or III symptoms.
  5. Stable doses of pulmonary vasodilators (prostacyclins, endothelin receptor antagonists, phosphodiesterase inhibitors), with no new therapy initiation or dose escalation > 50% in the 4 weeks prior to randomization.
  6. Age 18-80 years.

Exclusion criteria:

  1. Acute coronary syndrome or coronary revascularization within the prior 3 months.
  2. Patients with unstable angina.
  3. Patients with Class IV congestive heart failure.
  4. Planned revascularization, pacemaker or defibrillator placement during the study period.
  5. Changes in antianginal medical therapy likely to occur during the study period.
  6. Corrected QT interval measurement >500 ms.
  7. Patients with pre-existing QT prolongation (including congenital long QT syndrome) or receiving other QT prolonging drugs (including Class Ia-e.g., quinidine, Class III-e.g., dofetilide, sotalol, antiarrhythmics; antipsychotics (e.g., thioridazine, ziprasidone), or known history of complex ventricular arrhythmias requiring antiarrhythmic medications or ICD implantation.
  8. Patients with known history of hepatic dysfunction.
  9. Current use of strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir and diltizaem.
  10. Patients with pacemakers, cochlear implants, aneurysm clips, who have worked with metal.
  11. Patients with metallic hardware, implants, or prostheses will consult with the radiologist/cardiologist prior to the study.
  12. Patients with severe or end stage renal disease (an estimated GFR < 30 mL/min/1.73 m).
  13. Women who are pregnant or lactating
  14. Any contraindications for the use of a right heart catheter including, but not limited to:

    • Pulmonic or tricuspid valve stenosis
    • Prosthetic pulmonic or tricuspid valve
    • Right atrial or ventricular masses
    • Previous pneumonectomy
    • Risk of severe arrhythmias, including left bundle branch block (LBBB)
  15. Subjects unable to perform cardiopulmonary exercise testing will be excluded (i.e. extensive musculoskeletal disease)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01174173

Layout table for location information
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Gilead Sciences
Layout table for investigator information
Principal Investigator: Sanjiv Shah, MD Northwestern University
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Sanjiv Shah, Principal Invesitgator, Northwestern University
ClinicalTrials.gov Identifier: NCT01174173    
Other Study ID Numbers: STU00030314
First Posted: August 3, 2010    Key Record Dates
Results First Posted: April 23, 2015
Last Update Posted: May 11, 2018
Last Verified: April 2018
Keywords provided by Sanjiv Shah, Northwestern University:
Right Ventricular Ischemia
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Additional relevant MeSH terms:
Layout table for MeSH terms
Pulmonary Arterial Hypertension
Familial Primary Pulmonary Hypertension
Angina Pectoris
Vascular Diseases
Cardiovascular Diseases
Hypertension, Pulmonary
Lung Diseases
Respiratory Tract Diseases
Myocardial Ischemia
Heart Diseases
Chest Pain
Neurologic Manifestations
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action