Ranolazine and Pulmonary Hypertension

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
Sanjiv Shah, Northwestern University
ClinicalTrials.gov Identifier:
NCT01174173
First received: July 23, 2010
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

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 Intervention Phase
Angina
Pulmonary Arterial Hypertension
Drug: Ranolazine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Ranolazine in Patients With Angina Due to Right Ventricular Ischemia in Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Improve Angina Symptoms [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment

  • 6-Minute Walk Test [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
    Improve Exercise Capacity measured by 6-Minute Walk Test

  • Improve Quality of Life [ Time Frame: 3 Months ] [ Designated as safety issue: No ]
    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:
  • RV Perfusion on Cardiac MRI [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

  • Absolute RV Longitudinal Strain [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.

  • Right Ventricular Hemodynamics [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Mean pulmonary artery pressure was assessed invasively by right heart catheterization at the conclusion of the study to estimate right ventricular hemodynamics.


Enrollment: 11
Study Start Date: June 2010
Study Completion Date: October 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ranolazine
1000 mg PO BID
Drug: Ranolazine
ranolazine 1000 mg PO BID for 3 months
Other Name: Ranexa

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.

  Eligibility

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

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)
  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: NCT01174173

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Gilead Sciences
Investigators
Principal Investigator: Sanjiv Shah, MD Northwestern University
  More Information

Additional Information:
No publications provided

Responsible Party: Sanjiv Shah, Principal Invesitgator, Northwestern University
ClinicalTrials.gov Identifier: NCT01174173     History of Changes
Other Study ID Numbers: STU00030314
Study First Received: July 23, 2010
Results First Received: March 9, 2015
Last Updated: April 22, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Angina
Right Ventricular Ischemia
Pulmonary Arterial Hypertension
Pulmonary Hypertension

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

ClinicalTrials.gov processed this record on May 20, 2015