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| Name | Class |
|---|---|
| Gilead Sciences | INDUSTRY |
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The purpose of this study is to look at the effects of the drug Ranolazine compared to Placebo on symptoms of chest pain or chest tightness (known as angina), exercise endurance and ability, and changes in blood flow to the very small arteries of the heart (known as coronary microvascular function) in patients who do not have significant blockages in their major heart arteries. Ranolazine is a drug that is already approved by the FDA for angina, but it may be particularly effective in people with disease in their tiny heart vessels (known as coronary microvascular disease).
This trial aims to enroll 50 patients with angina who undergo baseline bicycle exercise testing with monitoring of the heart's electrical activity and oxygen consumption (known as cardiopulmonary exercise test) and coronary angiogram (taking pictures of the heart arteries through small hollow tubes placed through the wrist or groin). If severe blockages in the main arteries are not found then testing for coronary microvascular function will be performed. Subsequently, participants will then be randomized 50/50 to either Ranolazine or Placebo. After taking the study drug for 12 weeks, they will then repeat the cardiopulmonary exercise test and the coronary angiogram with testing for microvascular function.
Heart disease is the most common cause of death in the world. Most of our understanding of heart disease has involved the large heart arteries (epicardial arteries); however, disease of the very small heart arteries (coronary microvasculature) likely precedes the development of epicardial disease and represents the "base of the iceberg" of cardiovascular disease. Yet, we do not understand how dysfunctional microvasculature leads to reduced blood flow, symptoms and adverse outcomes.
Coronary microvascular disease results from a combination of structural and functional abnormalities, so it is important to have reliable diagnostic tools that do not rely solely on imaging. The gold-standard for testing involves hemodynamic (blood circulation) measurements such as coronary flow reserve (CFR) and hyperemic microcirculatory resistance (HMR) that take place in the cardiac catheterization laboratory.
Ranolazine is a relatively new U.S Food and Drug Administration-approved medicine to help with angina (chest pain). There are no publications on the effect of Ranolazine on HMR.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ranolazine | Experimental | Ranolazine 1,000 mg twice daily |
|
| Placebo | Placebo Comparator | Placebo twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ranolazine | Drug | Ranolazine 1,000 mg twice daily |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Seattle Angina Questionnaire Score Regarding Angina Frequency | The change in scores of the angina frequency dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina frequency dimension means that the participants are experiencing fewer episodes of angina at week 12 than they were at the baseline visit. | Baseline, Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Seattle Angina Questionnaire Score Regarding Physical Limitation | The change in scores of the physical limitation dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the physical limitation dimension means that the participants are experiencing less limitation at week 12 than they were at the baseline visit. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Habib Samady, MD | Emory University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Emory University | Atlanta | Georgia | 30322 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33272036 | Derived | Koh JS, Hung OY, Eshtehardi P, Kumar A, Rabah R, Raad M, Kumar S, Chaudhry S, Gupta S, Hosseini H, Brilakis E, Corban M, Sabbak N, Burnett GM, Liu C, Mehta PK, Quyyumi AA, Samady H. Microvascular Assessment of Ranolazine in Non-Obstructive Atherosclerosis: The MARINA Randomized, Double-Blinded, Controlled Pilot Trial. Circ Cardiovasc Interv. 2020 Dec;13(12):e008204. doi: 10.1161/CIRCINTERVENTIONS.119.008204. Epub 2020 Dec 4. | |
| 25760881 |
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Participants were recruited from Emory University Hospital in Atlanta, Georgia. Participant enrollment began in September 2014 and all study procedures were completed in June 2018.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ranolazine | Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks |
| FG001 | Placebo | Participants receiving a placebo to match the ranolazine dose for 12 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants completing the study are included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Ranolazine | Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks |
| BG001 | Placebo | Participants receiving a placebo to match the ranolazine dose for 12 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Change in Seattle Angina Questionnaire Score Regarding Angina Frequency | The change in scores of the angina frequency dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina frequency dimension means that the participants are experiencing fewer episodes of angina at week 12 than they were at the baseline visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
|
Adverse events were collected from the time of study enrollment until completion of follow-up (12 weeks)
The study investigators will record adverse effects, whether anticipated or unanticipated. All adverse events will be captured on an adverse event case report form and tracked from time of study enrollment until completion of all study follow-up (12 weeks).
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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 | Participants receiving 500mg twice a day for 2 weeks then 1000mg twice daily of ranolazine for 10 weeks |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Habib Samady, MD | Emory University | (404) 778-1237 | hsamady@emory.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 2, 2016 | Mar 29, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D017566 | Microvascular Angina |
| ID | Term |
|---|---|
| D000787 | Angina Pectoris |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular 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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| Placebo | Drug | Placebo |
|
| Baseline, Week 12 |
| Change in Seattle Angina Questionnaire Score Regarding Angina Stability | The change in scores of the angina stability dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina stability dimension means that the participants are experiencing fewer changes in their angina at week 12 than they were at the baseline visit. | Baseline, Week 12 |
| Change in Seattle Angina Questionnaire Score Regarding Treatment Satisfaction | The change in scores of the treatment satisfaction dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the treatment satisfaction dimension means that the participants are experiencing greater satisfaction with their treatment at week 12 than they were at the baseline visit. | Baseline, Week 12 |
| Change in Seattle Angina Questionnaire Score Regarding Disease Perception | The change in scores of the disease perception dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the disease perception dimension means that the participants felt that their disease impacted their quality of life less at week 12 than at the baseline visit. | Baseline, Week 12 |
| Change in Peak Rate of Oxygen Consumption (VO2 Max) | The change in VO2, as measured by cardiopulmonary exercise testing (CPET), after 12 weeks therapy with ranolazine compared with placebo. VO2 max is the maximum amount of oxygen the participants are utilizing during intense treatment. To standardize exercise stress testing, CPET was performed under the guidance of the MET-TEST CPET network in Atlanta, Georgia. The MET-TEST was created in 2003 and is a high-precision stress test with detailed physiological assessment, allowing accurate and reproducible measurements of peak VO2. Individuals may demonstrate an abnormal CPET response before they develop symptoms or present with cardiac events and abnormal CPET results are strong predictors of future adverse outcomes. Higher VO2 values indicate better oxygen utility and positive value for VO2 change means there was improvement from baseline at the week 12 visit. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. | Baseline, Week 12 |
| Change in Time to Angina | Change in time to angina as measured by cardiopulmonary exercise testing after 12 weeks therapy with Ranolazine compared with placebo. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. | Baseline, Week 12 |
| Change in Metabolic Equivalents of Task (METs) at Peak | Change in exercise was measured as Metabolic Equivalents of Task (METs) at Peak by cardiopulmonary exercise testing (CPET) after 12 weeks therapy with ranolazine compared with placebo. METs are used to describe functional aerobic capacity and harder physical tasks require a higher number of METs. METs at a peak level of exercise was determined for each participant. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for change in METs at Peak of exercise indicates that the participant has improved their aerobic capacity from baseline at the week 12 visit. | Baseline, Week 12 |
| Change in Coronary Flow Reserve (CFR) | The changes in Coronary Flow Reserve (CFR) after 12 weeks therapy with ranolazine compared with placebo are presented here. CFR is a measurement of the maximum increase of blood flow through the coronary arteries during exercise. Average peak velocity (APV) was assessed over a 3- to 5-beats period. CFR was defined as the ratio of hyperemic to basal APV. A low CFR is an indication of coronary artery disease. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for the change in CFR suggests improvement in coronary artery blood flow between the baseline and week 12 visits. | Baseline, Week 12 |
| Change in Hyperemic Microcirculatory Resistance (HMR) | Change in Hyperemic Microcirculatory Resistance (HMR) after 12 weeks therapy with ranolazine compared with placebo. Average peak velocity (APV) was assessed over a 3- to 5-beats period. HMR was measured as the ratio of distal pressure to APV. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Higher HMR is associated with myocardial ischemia and a positive value for change in HMR indicates increased risk for cardiac events at the week 12 visit. | Baseline, Week 12 |
| Percent Change in Coronary Blood Flow | Coronary endothelial function will also be evaluated by measurement of coronary blood flow during infusion of intracoronary acetylcholine. Coronary blood flow (CBF) is defined as diameter (D)2 x APV / 8. Percent change in CBF (%ΔCBF) is calculated by (CBFACh - CBFbaseline) / CBFbaseline x 100%, where a >50% increase in CBF in response to acetylcholine is considered normal. | Baseline, Week 12 |
| Derived |
| Titterington JS, Hung OY, Wenger NK. Microvascular angina: an update on diagnosis and treatment. Future Cardiol. 2015 Mar;11(2):229-42. doi: 10.2217/fca.14.79. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Hypertension | Count of Participants | Participants |
|
| Prior myocardial infarction | Count of Participants | Participants |
|
| OG001 |
| Placebo |
Participants receiving a placebo to match the ranolazine dose for 12 weeks |
|
|
| Secondary | Change in Seattle Angina Questionnaire Score Regarding Physical Limitation | The change in scores of the physical limitation dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the physical limitation dimension means that the participants are experiencing less limitation at week 12 than they were at the baseline visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
|
|
|
| Secondary | Change in Seattle Angina Questionnaire Score Regarding Angina Stability | The change in scores of the angina stability dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the angina stability dimension means that the participants are experiencing fewer changes in their angina at week 12 than they were at the baseline visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
|
|
|
| Secondary | Change in Seattle Angina Questionnaire Score Regarding Treatment Satisfaction | The change in scores of the treatment satisfaction dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the treatment satisfaction dimension means that the participants are experiencing greater satisfaction with their treatment at week 12 than they were at the baseline visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
|
|
|
| Secondary | Change in Seattle Angina Questionnaire Score Regarding Disease Perception | The change in scores of the disease perception dimension of the Seattle Angina Questionnaire (SAQ) after 12 weeks therapy with ranolazine or placebo are presented. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Individual dimensions of the Seattle Angina Questionnaire are transformed to be a score from 0 to 100, where higher scores indicate better health. A positive number for the disease perception dimension means that the participants felt that their disease impacted their quality of life less at week 12 than at the baseline visit. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 12 |
|
|
|
| Secondary | Change in Peak Rate of Oxygen Consumption (VO2 Max) | The change in VO2, as measured by cardiopulmonary exercise testing (CPET), after 12 weeks therapy with ranolazine compared with placebo. VO2 max is the maximum amount of oxygen the participants are utilizing during intense treatment. To standardize exercise stress testing, CPET was performed under the guidance of the MET-TEST CPET network in Atlanta, Georgia. The MET-TEST was created in 2003 and is a high-precision stress test with detailed physiological assessment, allowing accurate and reproducible measurements of peak VO2. Individuals may demonstrate an abnormal CPET response before they develop symptoms or present with cardiac events and abnormal CPET results are strong predictors of future adverse outcomes. Higher VO2 values indicate better oxygen utility and positive value for VO2 change means there was improvement from baseline at the week 12 visit. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. | Posted | Mean | Standard Deviation | L/min | Baseline, Week 12 |
|
|
|
| Secondary | Change in Time to Angina | Change in time to angina as measured by cardiopulmonary exercise testing after 12 weeks therapy with Ranolazine compared with placebo. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. | Data for this outcome measure was not collected. | Posted | Baseline, Week 12 |
|
|
| Secondary | Change in Metabolic Equivalents of Task (METs) at Peak | Change in exercise was measured as Metabolic Equivalents of Task (METs) at Peak by cardiopulmonary exercise testing (CPET) after 12 weeks therapy with ranolazine compared with placebo. METs are used to describe functional aerobic capacity and harder physical tasks require a higher number of METs. METs at a peak level of exercise was determined for each participant. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for change in METs at Peak of exercise indicates that the participant has improved their aerobic capacity from baseline at the week 12 visit. | Posted | Mean | Standard Deviation | 3.5ml of oxygen/kg per min | Baseline, Week 12 |
|
|
|
| Secondary | Change in Coronary Flow Reserve (CFR) | The changes in Coronary Flow Reserve (CFR) after 12 weeks therapy with ranolazine compared with placebo are presented here. CFR is a measurement of the maximum increase of blood flow through the coronary arteries during exercise. Average peak velocity (APV) was assessed over a 3- to 5-beats period. CFR was defined as the ratio of hyperemic to basal APV. A low CFR is an indication of coronary artery disease. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. A positive value for the change in CFR suggests improvement in coronary artery blood flow between the baseline and week 12 visits. | Posted | Mean | Standard Deviation | ratio of hyperemic to basal APV | Baseline, Week 12 |
|
|
|
| Secondary | Change in Hyperemic Microcirculatory Resistance (HMR) | Change in Hyperemic Microcirculatory Resistance (HMR) after 12 weeks therapy with ranolazine compared with placebo. Average peak velocity (APV) was assessed over a 3- to 5-beats period. HMR was measured as the ratio of distal pressure to APV. Change at 12 weeks was calculated as (Endpoint Value at 12 weeks - Endpoint Value at Baseline)/Endpoint Value at Baseline. Higher HMR is associated with myocardial ischemia and a positive value for change in HMR indicates increased risk for cardiac events at the week 12 visit. | Posted | Mean | Standard Deviation | mmHg/cm/s | Baseline, Week 12 |
|
|
|
| Secondary | Percent Change in Coronary Blood Flow | Coronary endothelial function will also be evaluated by measurement of coronary blood flow during infusion of intracoronary acetylcholine. Coronary blood flow (CBF) is defined as diameter (D)2 x APV / 8. Percent change in CBF (%ΔCBF) is calculated by (CBFACh - CBFbaseline) / CBFbaseline x 100%, where a >50% increase in CBF in response to acetylcholine is considered normal. | Data for this outcome measure was not collected. | Posted | Baseline, Week 12 |
|
|
| 0 |
| 11 |
| 0 |
| 11 |
| 0 |
| 11 |
| EG001 | Placebo | Participants receiving a placebo to match the ranolazine dose for 12 weeks | 0 | 11 | 0 | 11 | 0 | 11 |
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| D014652 |
| Vascular Diseases |
| Aniline Compounds |
| D000588 | Amines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |