Microvascular Coronary Disease In Women: Impact Of Ranolazine

NCT00570089 | Completed Phase 2 Results DMC

• 1 other identifier: IRB 10465
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.To evaluate the impact of ranolazine extended-release tablets in women with subendocardial ischemia due to microvascular endothelial dysfunction on myocardial ischemia (Cardiac Magnetic Resonance (CMR) extent, severity.
2. 2.To evaluate the impact of ranolazine extended-release tablets in women with subendocardial ischemia due to microvascular endothelial dysfunction on the outcomes of angina (Seattle Angina Questionnaire (SAQ), WISE angina frequency, Duke Activity Status Inventory(DASI) and SF-36).

Conditions

Myocardial Ischemia

Keywords

Ranolazine; Myocardial ischemia; Double blinded; Placebo controlled

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Seattle Angina Questionnaire (SAQ)

  4 weeks and 10 weeks

Study Arms (2)

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).

Drug: Ranolazine; Drug: Placebo

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.

Drug: Ranolazine; Drug: Placebo

Interventions

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.

Also known as: Ranexa

Placebo, Then Study Drug Ranexa(Ranolazine); Study Drug Ranexa, Then Placebo

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.

Placebo, Then Study Drug Ranexa(Ranolazine); Study Drug Ranexa, Then Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with signs and symptoms of myocardial ischemia (chest pain, abnormal stress testing, abnormal noninvasive testing) in the absence of obstructive coronary artery disease (epicardial coronary stenosis \<50% luminal diameter stenosis).
• Women with ≥10% myocardial ischemia by CMR perfusion.

You may not qualify if:

• Contraindications to withholding nitrates, beta-blockers, calcium channel agents, ACE/ARB agents for 48 hours prior to testing.
• Contraindications in CMR including AICD, pacemaker, untreatable claustrophobia or known angio-edema.
• Contraindications to ranolazine including hepatic insufficiency, prolonged QT, renal failure.
• Women taking drugs that inhibit CYP3A such as diltiazem, verapamil, ketoconazole, macrolides or HIV protease inhibitors.
• Women less than 18 years of age.
• Women on drugs that prolong the QT interval such as Class Ia or III antiarrhythmic agents, erythromycin, certain antipsychotics.
• Pregnancy or breast feeding.
• Life expectancy less than 6 months.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead
• CV Therapeutics: collaborator

Study Sites (1)

AHSP

Los Angeles, California, 90048, United States

Location

Related Publications (15)

• 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.

  PMID: 16717165 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.

  PMID: 10727587 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.

  PMID: 12882078 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.

  PMID: 10525488 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.

  PMID: 10821813 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.

  PMID: 12403662 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.

  PMID: 15197152 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.

  PMID: 11078769 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.

  PMID: 11756576 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.

  PMID: 9989961 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.

  PMID: 12860910 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.

  PMID: 12075055 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.

  PMID: 10851206 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.

  PMID: 15246641 BACKGROUND

• 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.

  PMID: 21565740 DERIVED

MeSH Terms

Conditions

Myocardial Ischemia

Interventions

Ranolazine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

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

Limitations and Caveats

This was a pilot study.

Results Point of Contact

• Title: C. Noel Bairey Merz, MD
• Organization: Cedars-Sinai Medical Center

merz@cshs.org

310-423-9680

Study Officials

• Noel Bairey-Merz, MD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: December 7, 2007
• First Posted: December 10, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: June 10, 2019
• Results First Posted: December 3, 2015

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

US (1)