Impact of Ranolazine in Blood Markers in Women With Angina and Metabolic Syndrome
Condition: Stable Angina; Metabolic Syndrome
MeSH terms: Angina Pectoris; Angina, Stable; Metabolic Syndrome; Syndrome
Intervention: Ranolazine; Placebo
Intervention description: Ranolazine 500 mg from baseline to week 3 and 1000 mg thereafter until week 24; Matching placebo tablets daily for 24 weeks.
Intervention MeSH terms: Ranolazine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 33.0
Sex: Female
Minimum age: 30 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Stable Angina; Metabolic Syndrome; Women; Biomarkers

Summary:

      The purpose of this study is to determine the effects of ranolazine on different markers of
      cardiometabolic disease in women with stable angina.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with chronic stable angina (> 3 months) on evidence based adequate therapy

          -  Evidence of stable coronary artery disease by any of these:

          -  MI, PCI or CABG > 30 days prior to enrollment or

          -  Angiography showing > 50% stenosis in major vessel, branch or bypass graft > 30 days
             of enrollment or

          -  Abnormal stress MPI nuclear study, or DBA stress echo where the decision has been to
             treat medically and where angina has remained stable for >= 3 months

          -  Evidence of the Metabolic Syndrome: As defined by ATP III criteria i.e 3/5 of
             following Abdominal circumference F > 88 cm (35 in), M > 102 cm (40 in)
             Hypertriglyceridemia ≥ 150 mg/dl HDL F < 50 mg/dl M < 40 mg/dl Blood Pressure ≥130/85
             Fasting Glucose ≥100 mg/dl For reproductive age women, a negative urine pregnancy test
             is required if all other inclusion criteria are met.

        Exclusion Criteria:

          -  Exclusion of patients with contraindications to use of RANEXA, including patients on
             CYP3A4 inducers/potent inhibitors, and patients with liver cirrhosis.

          -  Exclusion of Patients with CrCl < 30 mL/min

          -  Limit dose of RANEXA to 500mg BID in patients on concurrent diltiazem/ verapamil

          -  Limit concurrent simvastatin to 20 mg/day

          -  Limit concurrent metformin to 1700 mg/day Additional Exclusion

          -  Patients with variable -inconsistent symptoms

          -  Patients with unstable coronary artery disease or revascularization within 30 days of
             enrollment.

          -  Patients who have known severe liver disease.

          -  Patients already receiving maximal ranolazine therapy for more than 4 weeks

          -  Presence of diabetes (AIC≥ 6.5 and /or on insulin therapy or anti-diabetic medication
             other than metformin) unstable hypothyroidism, active infection, active cancer (or
             ongoing chemotherapy and/or radiation within a year who are not on remission) and/or
             recent major surgery or illness.

          -  Patients with any contraindication to ranolazine see above

          -  Women of reproductive age are excluded if they are planning to become pregnant in the
             next 6 -12 months after randomization.

          -  Patients who are pregnant or lactating

          -  Documented allergic reaction to ranolazine in the past.

          -  Unexplained prolongation of the QTc > 500 milliseconds.

          -  Current or planned co-administration of moderate CYP3A inhibitors (eg, diltiazem,
             verapamil, aprepitant, erythromycin, fluconazole, and grapefruit juice or
             grapefruit-containing products) is not a full contraindication, if meet inclusion
             criteria otherwise, these patients could be accepted in trial but dose will be limited
             to 500 mg BID as stated previously.

          -  Current or planned co-administration of strong CYP3A inhibitors (eg, ketoconazole,
             itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and
             saquinavir) OR strong CYP3A inducers (eg, rifampin, rifabutin, rifapentine,
             phenobarbital, phenytoin,carbamazepine, and St. John's Wort) is a contraindication.