Ranolazine and Pulmonary Hypertension

NCT01174173 | Completed Phase 3 Results

• 1 other identifier: STU00030314
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

Angina; Pulmonary Arterial Hypertension

Keywords

Angina; Right Ventricular Ischemia; Pulmonary Arterial Hypertension; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (3)

• Improve Angina Symptoms

  Assessed as average improvement in WHO Functional Class. The WHO Functional Class score ranges from 1 to 4, with higher scores indicating more impairment

  3 months

• 6-Minute Walk Test

  Improve Exercise Capacity measured by 6-Minute Walk Test

  3 Months

• Improve Quality of Life

  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.

  3 Months

Secondary Outcomes (3)

• RV Perfusion on Cardiac MRI

  3 months

• Absolute RV Longitudinal Strain

  3 months

• Right Ventricular Hemodynamics

  3 months

Study Arms (1)

Ranolazine

EXPERIMENTAL

1000 mg PO BID

Drug: Ranolazine

Interventions

Ranolazine DRUG

ranolazine 1000 mg PO BID for 3 months

Also known as: Ranexa

Ranolazine

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Right ventricular dysfunction, defined as RV fractional area change \< 32% or RV tricuspid annular plane systolic excursion (TAPSE) \< 15 mm.
• Symptoms of angina or angina equivalent (exertional dyspnea, exertional epigastric pain, exertional nausea).
• New York Heart Association functional class II or III symptoms.
• 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.
• Age 18-80 years.

You may not qualify if:

• Acute coronary syndrome or coronary revascularization within the prior 3 months.
• Patients with unstable angina.
• Patients with Class IV congestive heart failure.
• Planned revascularization, pacemaker or defibrillator placement during the study period.
• Changes in antianginal medical therapy likely to occur during the study period.
• Corrected QT interval measurement \>500 ms.
• 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.
• Patients with known history of hepatic dysfunction.
• Current use of strong CYP3A inhibitors, including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir and diltizaem.
• Patients with pacemakers, cochlear implants, aneurysm clips, who have worked with metal.
• Patients with metallic hardware, implants, or prostheses will consult with the radiologist/cardiologist prior to the study.
• Patients with severe or end stage renal disease (an estimated GFR \< 30 mL/min/1.73 m).
• Women who are pregnant or lactating
• Any contraindications for the use of a right heart catheter including, but not limited to:
• Pulmonic or tricuspid valve stenosis

Sponsors & Collaborators

• Northwestern University: lead
• Gilead Sciences: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• 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.

  PMID: 26401256 DERIVED

Related Links

• Bluhm Cardiovascular Institute Clinical Trials Unit research studies

MeSH Terms

Conditions

Angina Pectoris; Pulmonary Arterial Hypertension; Hypertension, Pulmonary

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Hypertension

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

This study was a small pilot Interventional study to test safety and tolerability of ranolazine in 11 patients with sx WHO Group 1 PAH patients.

Results Point of Contact

• Title: Sanjiv J. Shah, MD
• Organization: Northwestern University

sanjiv.shah@northwestern.edu

3129262926

Study Officials

• Sanjiv Shah, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Invesitgator

Study Record Dates

• First Submitted: July 23, 2010
• First Posted: August 3, 2010
• Study Start: June 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: October 1, 2014
• Last Updated: May 11, 2018
• Results First Posted: April 23, 2015

Record last verified: 2018-04

Locations

US (1)