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| Name | Class |
|---|---|
| Gilead Sciences | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ranolazine | Experimental | 1000 mg PO BID |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ranolazine | Drug | ranolazine 1000 mg PO BID for 3 months |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| RV Perfusion on Cardiac MRI | 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. | 3 months |
| Absolute RV Longitudinal Strain |
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Inclusion criteria:
Exclusion criteria:
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:
Subjects unable to perform cardiopulmonary exercise testing will be excluded (i.e. extensive musculoskeletal disease)
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| Name | Affiliation | Role |
|---|---|---|
| Sanjiv Shah, MD | Northwestern University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University | Chicago | Illinois | 60611 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26401256 | Derived | 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. |
| Label | URL |
|---|---|
| Bluhm Cardiovascular Institute Clinical Trials Unit research studies | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ranolazine | 1000 mg PO BID Ranolazine: ranolazine 1000 mg PO BID for 3 months |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
We prospectively enrolled 11 patients with WHO Group 1 PAH with mean age was 48±13 years and 73% of patients were women. Nearly half of the study participants were non-white.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ranolazine | 1000 mg PO BID Ranolazine: ranolazine 1000 mg PO BID for 3 months |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | Analysis was performed on all participants who completed as average change in WHO Functional class score from baseline to 3 months (Baseline, 3 months) | Posted | Mean | Standard Deviation | units on a scale | 3 months |
|
|
3 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ranolazine | Ranolazine: ranolazine 1000 mg PO BID for 3 months |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Inpatient hospitalization | Nervous system disorders | Non-systematic Assessment | 1 patient reported symptoms of dizziness, leg weakness, and hand tremors; Because of possibility of an interaction between ranolazine and darifenacin, ranolazine was discontinued, patient withdrawn from the study, and had complete resolution. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myalgias | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sanjiv J. Shah, MD | Northwestern University | 3129262926 | sanjiv.shah@northwestern.edu |
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| ID | Term |
|---|---|
| D000787 | Angina Pectoris |
| D000081029 | Pulmonary Arterial Hypertension |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000069458 | Ranolazine |
| ID | Term |
|---|---|
| D000083 | Acetanilides |
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 |
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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. |
| 3 months |
| Right Ventricular Hemodynamics | Mean pulmonary artery pressure was assessed invasively by right heart catheterization at the conclusion of the study to estimate right ventricular hemodynamics. | 3 months |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Exercise stress echocardiography with strain | Mean | Standard Deviation | Ejection Fraction (%) |
|
| Right heart catheterization | Mean | Standard Deviation | Mean pulmonary artery pressure (mm Hg) |
|
| 6-minute walk test | Mean | Standard Deviation | meters |
|
|
|
|
| Primary | 6-Minute Walk Test | Improve Exercise Capacity measured by 6-Minute Walk Test | Analysis was performed in all participants who completed the study and had a 6-minute walk test at baseline and at the conclusion of the study. | Posted | Mean | Standard Deviation | meters | 3 Months |
|
|
|
|
| Primary | 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. | Analysis was performed on the 8 participants who completed the KCCQ questionnaire at baseline and at the conclusion of the study (month 3) | Posted | Mean | Standard Deviation | KCCQ Summary Score | 3 Months |
|
|
|
|
| Secondary | RV Perfusion on Cardiac MRI | 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. | Posted | 3 months |
|
|
| Secondary | Absolute RV Longitudinal Strain | 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. | Analysis was performed on all participants who completed exercise stress echocardiography at baseline and conclusion of the study (month 3) | Posted | Mean | Standard Deviation | percentage | 3 months |
|
|
|
|
| Secondary | Right Ventricular Hemodynamics | Mean pulmonary artery pressure was assessed invasively by right heart catheterization at the conclusion of the study to estimate right ventricular hemodynamics. | Analysis was performed on all participants who completed right heart catheterization at the conclusion of the study | Posted | Mean | Standard Deviation | mm Hg | 3 months |
|
|
|
|
| 1 |
| 11 |
| 6 |
| 11 |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | Systematic Assessment |
|
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| D002637 |
| Chest Pain |
| D010146 | Pain |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| Aniline Compounds |
| D000588 | Amines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |