Impact of Ranolazine in Blood Markers in Women With Angina and Metabolic Syndrome (IRMA)

Impact of Ranolazine on Inflammatory, Thrombogenic, Lipogenic, Biomarkers in Women With Angina and Metabolic Syndrome.

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

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Stable Angina
• Intervention / Treatment: Drug: Ranolazine; Other: Placebo

Detailed Description

Evaluate the ability of ranolazine to favorably modify thrombogenic, inflammatory, lipogenic, oxidative stress and hormonal biomarkers in a relatively short period of time in a group of ethnically diverse women with chronic stable angina and metabolic syndrome.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ranolazine; Ranolazine would start with 500 mg BID and be force titrated to 1 gram po BID after 3 weeks. Down titration would only be allowed for side effects. This would be on top of all standard medical therapy.	Drug: Ranolazine; Ranolazine 500 mg from baseline to week 3 and 1000 mg thereafter until week 24; Other Names: Ranexa
Placebo Comparator: Placebo; Placebo arm would start with 500 mg matching placebo tablet BID and be force titrated to 1 gram matching placebo tablet twice a day after 3 weeks. Down titration would only be allowed for side effects (if reported). This would be on top of all standard medical therapy.	Other: Placebo; Matching placebo tablets daily for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of Ranolazine on Hemoglobin A1C	Will evaluate the impact of ranolazine in HgbA1C in women with Metabolic Syndrome (MBS)	Change from baseline to 24 weeks
Impact of Ranolazine on HDL-C Levels in Subjects	Will evaluate the impact of ranolazine in HDL-C levels in women with metabolic syndrome	Change from Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: University of Florida
• Investigators: Principal Investigator: Gladys P Velarde, MD, FACC, University of Florida

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 17, 2018
• Study Completion (Actual): May 17, 2019

Study Registration Dates

• First Submitted: August 11, 2014
• First Submitted That Met QC Criteria: September 25, 2014
• First Posted (Estimate): September 30, 2014

Study Record Updates

• Last Update Posted (Actual): April 10, 2020
• Last Update Submitted That Met QC Criteria: March 27, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Stable Angina; Women; Metabolic Syndrome; Biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Pain; Neurologic Manifestations; Disease; Insulin Resistance; Hyperinsulinism; Chest Pain; Syndrome; Metabolic Syndrome; Angina Pectoris; Angina, Stable; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Sodium Channel Blockers; Ranolazine
• Other Study ID Numbers: WIRB20141202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No