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| Name | Class |
|---|---|
| CV Therapeutics | INDUSTRY |
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Interested women will be considered for the study if they meet inclusion and exclusion criteria including review of baseline CMR, ECG and blood work (liver and kidney function). The baseline CMR must be completed within 12 months previous to enrollment.
Eligible women with angina and CMR subendocardial perfusion abnormalities, defined as CMR qualitative perfusion abnormalities of greater than or equal to 10% reported as abnormal following blind review per protocol, will be consented and enrolled. The women will complete baseline demographic and health history questionnaires, including the SAQ, Women's Ischemic Syndrome Evaluation (WISE) angina frequency, DASI and SF-36.
This study is a double-blind, placebo controlled, cross-over design in which treatment order to ranolazine and placebo will be randomly assigned. Note: The participant's usual medication regimen will be continued throughout study participation. Following enrollment into the study, participants will be randomized to treatment #1 (either placebo or ranolazine). Ranolazine will be dosed as 500 mg orally twice daily for 2 weeks and, assuming tolerance, followed by 1000 mg orally twice daily for an additional 2 weeks. If the participant is unable to increase dose secondary to side effects, she will remain on 500 mg twice daily for the second 2 week interval. The first end of treatment CMR (CMR 1) will be scheduled at the end of the 4th week of treatment, approximately 4 hours after the morning dose of study drug. At this visit (Vis 2), concurrent medications, symptoms, and adverse events will be reviewed. Clinical measurements will be taken (weight, BP, waist and hip circumference) and questionnaires will be completed (SAQ, WISE angina frequency, DASI and SF-36).
After the first course of study treatment, the patient will undergo a two week wash-out with no study drug while continuing usual medication regimen. Following the washout period, study participants will start the second cycle of study drug treatment (i.e., the other study drug not received in treatment 1). At visit 3, participants will undergo baseline 2 measurements which include concurrent medication and symptom assessment, clinical measurements (weight, BP, waist and hip circumference) and will complete baseline 2 questionnaires (SAQ, WISE angina frequency, DASI and SF-36). Study drug treatment #2 will follow the same escalation of study drug dose as described above for treatment 1. The final study CMR (CMR 2) will be scheduled at the end of the 4th week of treatment 2, approximately 4 hours after the morning dose of study drug. At this visit (Vis 4), concurrent medications, symptoms, and adverse events will be reviewed. Clinical measurements will be taken (weight, blood pressure, waist and hip circumference) and questionnaires will be completed (SAQ, WISE angina frequency, DASI and SF-36). [See Table 1 for a listing of all study procedures by visit.] The two post study drug treatment CMRs will be performed at the same time of day, replicating temperature, fasting state, adenosine dosing and infusion, magnet settings and using the same over-reader. The dose of adenosine will be consistent for all study CMR tests: 140 mcg/kg over 5 minutes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Study Drug Ranexa, Then Placebo | Experimental | Participants first received study drug Ranexa, 500mg, orally twice daily for 2 weeks, assuming tolerance, followed by 1000mg orally twice daily for an additional 2 weeks. If the participant is unable to increase dose secondary to side effects, she will remain on 500mg twice daily for the second 2-week interval. After a washout period of 2 weeks, they then received Placebo tablet (matching Ranexa tablet). |
|
| Placebo, Then Study Drug Ranexa(Ranolazine) | Experimental | Participants first received Placebo tablet (matching Ranexa tablet) for two weeks. After washout period of 2 weeks, they then received Ranexa 500mg, orally twice daily for 2 weeks, assuming tolerance, followed by 1000mg orally twice daily for an additional 2 weeks. If the participant is unable to increase dose secondary to side effects, she will remain on 500mg twice daily for the second 2-week interval. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ranolazine | Drug | 500mg, orally twice daily for 2 weeks, assuming tolerance, followed by 1000mg orally twice daily for an additional 2 weeks. If the participant is unable to increase dose secondary to side effects, she will remain on 500mg twice daily for the second 2-week interval. |
| Measure | Description | Time Frame |
|---|---|---|
| Cardiac Magnetic Resonance (CMRs) | Cardiac Magnetic Resonance (CMRs) (CMR 1 and CMR 2) end of the 4th week of treatment 1 and treatment 2 respectively, 4 hours after the morning dose of study drug was performed to measure myocardial perfusion defect in percentage. | 4 weeks and 10 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Seattle Angina Questionnaire (SAQ) | Questionnaires will be completed (SAQ - Seattle Angina Questionnaire) at the end of each treatment period. The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important. Each final SAQ domain ranges from 0-100, where higher is a better outcome score. Subscales are not combined. Median, SD and range are calculated for each domain. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Noel Bairey-Merz, MD | Cedars-Sinai Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| AHSP | Los Angeles | California | 90048 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16717165 | Background | Chaitman BR. Ranolazine for the treatment of chronic angina and potential use in other cardiovascular conditions. Circulation. 2006 May 23;113(20):2462-72. doi: 10.1161/CIRCULATIONAHA.105.597500. No abstract available. | |
| 10727587 | Background | Buchthal SD, den Hollander JA, Merz CN, Rogers WJ, Pepine CJ, Reichek N, Sharaf BL, Reis S, Kelsey SF, Pohost GM. Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms. N Engl J Med. 2000 Mar 23;342(12):829-35. doi: 10.1056/NEJM200003233421201. |
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This is a cross-over study. 20 subjects (10 in study drug arm and 10 in placebo arm) completed period 1. In period 2, the 10 subjects who were on study drug in period 1 were on placebo arm in period 2, and the 10 subjects who were on placebo arm in period 1 were on study drug arm in period 2. The 20 subjects had a 2-week wash out in between.
20 subjects were recruited at Cedars-Sinai Medical Center Cardiology outpatient clinic.
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| ID | Title | Description |
|---|---|---|
| FG000 | Study Drug Ranexa Then Placebo | 20 subjects (10 in study drug arm and 10 in placebo arm) completed period 1. In period 2, the 10 subjects who were on study drug in period 1 were on placebo arm in period 2, and the 10 subjects who were on placebo arm in period 1 were on study drug arm in period 2. The 20 subjects had a 2-week wash out in between. |
| FG001 | Placebo Then Study Drug Ranexa | 20 subjects (10 in study drug arm and 10 in placebo arm) completed period 1. In period 2, the 10 subjects who were on study drug in period 1 were on placebo arm in period 2, and the 10 subjects who were on placebo arm in period 1 were on study drug arm in period 2. The 20 subjects had a 2-week wash out in between. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Perod 2 |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Study Participants | Participants who were randomized to receive either Study drug Ranexa or Placebo. |
| 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 | Cardiac Magnetic Resonance (CMRs) | Cardiac Magnetic Resonance (CMRs) (CMR 1 and CMR 2) end of the 4th week of treatment 1 and treatment 2 respectively, 4 hours after the morning dose of study drug was performed to measure myocardial perfusion defect in percentage. | Posted | Median | Full Range | Percentage of ischemic myocardium | 4 weeks and 10 weeks |
|
10 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 | Study Drug | Study drug Ranexa arm |
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This was a pilot study.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| C. Noel Bairey Merz, MD | Cedars-Sinai Medical Center | 310-423-9680 | merz@cshs.org |
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| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| ID | Term |
|---|---|
| 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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|
|
| Placebo | Drug | Placebo, 500mg, orally twice daily for 2 weeks, assuming tolerance, followed by 1000mg orally twice daily for an additional 2 weeks. If the participant is unable to increase dose secondary to side effects, she will remain on 500mg twice daily for the second 2-week interval. |
|
| 4 weeks and 10 weeks |
| 12882078 | Background | Doyle M, Fuisz A, Kortright E, Biederman RW, Walsh EG, Martin ET, Tauxe L, Rogers WJ, Merz CN, Pepine C, Sharaf B, Pohost GM. The impact of myocardial flow reserve on the detection of coronary artery disease by perfusion imaging methods: an NHLBI WISE study. J Cardiovasc Magn Reson. 2003 Jul;5(3):475-85. doi: 10.1081/jcmr-120022263. |
| 10525488 | Background | Hundley WG, Hamilton CA, Thomas MS, Herrington DM, Salido TB, Kitzman DW, Little WC, Link KM. Utility of fast cine magnetic resonance imaging and display for the detection of myocardial ischemia in patients not well suited for second harmonic stress echocardiography. Circulation. 1999 Oct 19;100(16):1697-702. doi: 10.1161/01.cir.100.16.1697. |
| 10821813 | Background | Hundley WG, Hillis LD, Hamilton CA, Applegate RJ, Herrington DM, Clarke GD, Braden GA, Thomas MS, Lange RA, Peshock RM, Link KM. Assessment of coronary arterial restenosis with phase-contrast magnetic resonance imaging measurements of coronary flow reserve. Circulation. 2000 May 23;101(20):2375-81. doi: 10.1161/01.cir.101.20.2375. |
| 12403662 | Background | Hundley WG, Morgan TM, Neagle CM, Hamilton CA, Rerkpattanapipat P, Link KM. Magnetic resonance imaging determination of cardiac prognosis. Circulation. 2002 Oct 29;106(18):2328-33. doi: 10.1161/01.cir.0000036017.46437.02. |
| 15197152 | Background | Johnson BD, Shaw LJ, Buchthal SD, Bairey Merz CN, Kim HW, Scott KN, Doyle M, Olson MB, Pepine CJ, den Hollander J, Sharaf B, Rogers WJ, Mankad S, Forder JR, Kelsey SF, Pohost GM; National Institutes of Health-National Heart, Lung, and Blood Institute. Prognosis in women with myocardial ischemia in the absence of obstructive coronary disease: results from the National Institutes of Health-National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation. 2004 Jun 22;109(24):2993-9. doi: 10.1161/01.CIR.0000130642.79868.B2. Epub 2004 Jun 14. |
| 11078769 | Background | Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000 Nov 16;343(20):1445-53. doi: 10.1056/NEJM200011163432003. |
| 11756576 | Background | Kim WY, Danias PG, Stuber M, Flamm SD, Plein S, Nagel E, Langerak SE, Weber OM, Pedersen EM, Schmidt M, Botnar RM, Manning WJ. Coronary magnetic resonance angiography for the detection of coronary stenoses. N Engl J Med. 2001 Dec 27;345(26):1863-9. doi: 10.1056/NEJMoa010866. |
| 9989961 | Background | Nagel E, Lehmkuhl HB, Bocksch W, Klein C, Vogel U, Frantz E, Ellmer A, Dreysse S, Fleck E. Noninvasive diagnosis of ischemia-induced wall motion abnormalities with the use of high-dose dobutamine stress MRI: comparison with dobutamine stress echocardiography. Circulation. 1999 Feb 16;99(6):763-70. doi: 10.1161/01.cir.99.6.763. |
| 12860910 | Background | Nagel E, Klein C, Paetsch I, Hettwer S, Schnackenburg B, Wegscheider K, Fleck E. Magnetic resonance perfusion measurements for the noninvasive detection of coronary artery disease. Circulation. 2003 Jul 29;108(4):432-7. doi: 10.1161/01.CIR.0000080915.35024.A9. Epub 2003 Jul 14. |
| 12075055 | Background | Panting JR, Gatehouse PD, Yang GZ, Grothues F, Firmin DN, Collins P, Pennell DJ. Abnormal subendocardial perfusion in cardiac syndrome X detected by cardiovascular magnetic resonance imaging. N Engl J Med. 2002 Jun 20;346(25):1948-53. doi: 10.1056/NEJMoa012369. |
| 10851206 | Background | Schwitter J, DeMarco T, Kneifel S, von Schulthess GK, Jorg MC, Arheden H, Ruhm S, Stumpe K, Buck A, Parmley WW, Luscher TF, Higgins CB. Magnetic resonance-based assessment of global coronary flow and flow reserve and its relation to left ventricular functional parameters: a comparison with positron emission tomography. Circulation. 2000 Jun 13;101(23):2696-702. doi: 10.1161/01.cir.101.23.2696. |
| 15246641 | Background | Wahl A, Paetsch I, Gollesch A, Roethemeyer S, Foell D, Gebker R, Langreck H, Klein C, Fleck E, Nagel E. Safety and feasibility of high-dose dobutamine-atropine stress cardiovascular magnetic resonance for diagnosis of myocardial ischaemia: experience in 1000 consecutive cases. Eur Heart J. 2004 Jul;25(14):1230-6. doi: 10.1016/j.ehj.2003.11.018. |
| 21565740 | Derived | Mehta PK, Goykhman P, Thomson LE, Shufelt C, Wei J, Yang Y, Gill E, Minissian M, Shaw LJ, Slomka PJ, Slivka M, Berman DS, Bairey Merz CN. Ranolazine improves angina in women with evidence of myocardial ischemia but no obstructive coronary artery disease. JACC Cardiovasc Imaging. 2011 May;4(5):514-22. doi: 10.1016/j.jcmg.2011.03.007. |
| NOT COMPLETED |
|
| Participants |
|
| Age, Continuous | Mean | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Seattle Angina Questionnaire (SAQ) | Questionnaires will be completed (SAQ - Seattle Angina Questionnaire) at the end of each treatment period. The Seattle Angina Questionnaire (SAQ) is a self-administered, 19-item questionnaire, a cardiac disease-related quality-of-life measure. The SAQ is well validated and sensitive to clinical changes. It has five subscales: physical limitation, angina stability, angina frequency, treatment satisfaction, and disease perception. The possible range of scores for each of the five subscales is 0 to 100, with higher scores indicating better quality of life. A change of 10 points in any of the subscales is considered to be clinically important. Each final SAQ domain ranges from 0-100, where higher is a better outcome score. Subscales are not combined. Median, SD and range are calculated for each domain. | Posted | Median | Full Range | units on a scale | 4 weeks and 10 weeks |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| EG001 | Placebo | Placebo arm | 0 | 20 | 0 | 20 |
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| Aniline Compounds |
| D000588 | Amines |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| Angina Frequency |
|
| Treatment Satisfaction |
|
| Quality of Life |
|