Microvascular Coronary Disease In Women: Impact Of Ranolazine

This study has been completed.
Sponsor:
Collaborator:
CV Therapeutics
Information provided by:
Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00570089
First received: December 7, 2007
Last updated: March 23, 2010
Last verified: March 2010
  Purpose
  1. To evaluate the impact of ranolazine extended-release tablets in women with subendocardial ischemia due to microvascular endothelial dysfunction on myocardial ischemia (CMR extent, severity).
  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 (SAQ, WISE angina frequency, DASI and SF-36).

Condition Intervention Phase
Myocardial Ischemia
Drug: Ranolazine
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Microvascular Coronary Disease In Women: Impact Of Ranolazine

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • 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 [ Time Frame: 60 minutes each CMR ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Questionnaires will be completed (SAQ, WISE angina frequency, DASI and SF-36) [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: April 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Study drug Drug: Ranolazine
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.
Other Name: Ranexa
Placebo Comparator: Placebo Drug: Placebo
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.

Detailed Description:

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, 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, BP, 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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).
  2. Women with ≥10% myocardial ischemia by CMR perfusion.

Exclusion Criteria:

  1. Contraindications to withholding nitrates, beta-blockers, calcium channel agents, ACE/ARB agents for 48 hours prior to testing.
  2. Contraindications in CMR including AICD, pacemaker, untreatable claustrophobia or known angio-edema.
  3. Contraindications to ranolazine including hepatic insufficiency, prolonged QT, renal failure.
  4. Women taking drugs that inhibit CYP3A such as diltiazem, verapamil, ketoconazole, macrolides or HIV protease inhibitors.
  5. Women less than 18 years of age.
  6. Women on drugs that prolong the QT interval such as Class Ia or III antiarrhythmic agents, erythromycin, certain antipsychotics.
  7. Pregnancy or breast feeding.
  8. Life expectancy less than 6 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00570089

Locations
United States, California
Mark Goodson Building
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
CV Therapeutics
Investigators
Principal Investigator: Noel Bairey-Merz, MD Cedars-Sinai Medical Center
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: C. Noel Bairey Merz, MD, Cedars Sinai Medical Center
ClinicalTrials.gov Identifier: NCT00570089     History of Changes
Other Study ID Numbers: IRB 10465
Study First Received: December 7, 2007
Last Updated: March 23, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Cedars-Sinai Medical Center:
Ranolazine
Myocardial ischemia
Double blinded
Placebo controlled

Additional relevant MeSH terms:
Myocardial Ischemia
Coronary Artery Disease
Coronary Disease
Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Pathologic Processes
Ranolazine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014