Ranolazine and Pulmonary Hypertension

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Collaborator: Gilead Sciences
• Treatments: Ranolazine

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)