Clinical trial NCT01174173: Ranolazine and Pulmonary Hypertension
Official title: Effects of Ranolazine in Patients With Angina Due to Right Ventricular Ischemia in Pulmonary Arterial Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Angina
Pulmonary Arterial Hypertension
Keywords: Angina
Right Ventricular Ischemia
Pulmonary Arterial Hypertension
Pulmonary Hypertension
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Gilead Sciences
First posted: 2010-08-03
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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)

Primary outcomes:
measure: Improve Angina Symptoms
timeFrame: 3 months
measure: 6-Minute Walk Test
timeFrame: 3 Months
measure: Improve Quality of Life
timeFrame: 3 Months
Secondary outcomes:
measure: RV Perfusion on Cardiac MRI
timeFrame: 3 months
measure: Absolute RV Longitudinal Strain
timeFrame: 3 months
measure: Right Ventricular Hemodynamics
timeFrame: 3 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
Study officials:
affiliation: Northwestern University
name: Sanjiv Shah, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Khan SS, Cuttica MJ, Beussink-Nelson L, Kozyleva A, Sanchez C, Mkrdichian H, Selvaraj S, Dematte JE, Lee DC, Shah SJ. Effects of ranolazine on exercise capacity, right ventricular indices, and hemodynamic characteristics in pulmonary arterial hypertension: a pilot study. Pulm Circ. 2015 Sep;5(3):547-56. doi: 10.1086/682427.