Ranolazine and Pulmonary Hypertension

NCT ID: NCT01174173

Last Updated: 2018-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-10-31

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.

Conditions

Angina; Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ranolazine

1000 mg PO BID

Group Type: EXPERIMENTAL

Ranolazine

Intervention Type: DRUG

ranolazine 1000 mg PO BID for 3 months

Interventions

Ranolazine

ranolazine 1000 mg PO BID for 3 months

Intervention Type: DRUG

Other Intervention Names

Ranexa

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Sanjiv Shah

Principal Invesitgator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sanjiv Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 26401256 (View on PubMed)

Related Links

http://www.feinberg.northwestern.edu/ctu/current_research/heart_failure/index.htm

Bluhm Cardiovascular Institute Clinical Trials Unit research studies

Other Identifiers

STU00030314

Identifier Type: -

Identifier Source: org_study_id