Safety of Amiodarone and Ranolazine Together in Patients With Angina

Study Overview
=================
Brief Summary
-----------------
Ranolazine is an effective and remarkably safe agent for the treatment of patients with chronic stable angina, but its inhibition of voltage gated potassium channels and electrocardiogram (EKG) corrected QT (QTc) prolongation properties have lead many to question its safety when combined with antiarrhythmic drugs. The investigators have proposed a study to determine the safety of ranolazine in patients with chronic stable angina who also take amiodarone. And are conducting a prospective single-center randomized single-blinded placebo controlled trial to run out of our large cardiology practice setting at Cardiovascular Consultants of Nevada. The hypothesis is that there will be no difference in the ventricular arrhythmia burden. The primary outcome will be the measurement of ventricular arrhythmia episodes on serial holter monitor and other serially acquired recordings (such as electrocardiogram, pacemaker or implantable defibrillator (ICD) data, and stress test data) over a three month trial period.

Official Title
-----------------
Safety of Amiodarone and Ranolazine Together in Patients With Stable Angina

Conditions
-----------------
Chronic Stable Angina, Coronary Artery Disease, Atrial Fibrillation, Ventricular Tachycardia

Intervention / Treatment
-----------------
* Drug: ranolazine
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ischemic cardiac disease chronic anginal symptoms on amiodarone therapy for other cardiac conditions Exclusion Criteria: pregnant non-English speaking unstable angina baseline electrocardiogram (EKG) corrected QT (QTc)>490ms severe thyroid dysfunction heart block without a pacer system liver disease

Ages Eligible for Study
-----------------
Minimum Age: 35 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: sugar pill<br>one pill twice daily, uptitrated to two pills twice daily to mirror ranolazine prescription strategy | Drug: placebo<br>* one pill twice daily, to increase to two pills twice daily to mirror standard ranolazine treatment strategy<br>|
| Active Comparator: Ranolazine<br>500 mg twice daily, titrated to 1000 mg twice daily if needed for relief of anginal symptoms | Drug: ranolazine<br>* ranolazine 500mg twice daily, may increase to 1000 mg twice daily for therapy optimization in treating chronic stable angina<br>* Other names: Ranexa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ventricular arrhythmia | primary outcome is the burden of ventricular arrhythmias measured on serial holter monitor recordings, stress test recordings, pacemaker or implantable defibrillator (ICD) recordings if available, at baseline and serially to trial completion. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| atrial arrhythmia burden | burden of atrial arrhythmias will be measured on serial holter monitor recordings | 3 months | 
| Electrocardiogram (EKG) corrected QT (QTc) interval measurement | The electrocardiogram (EKG) corrected QT (QTc) interval be quantitated at baseline and serially to trial completion | over the 3 month trial | 
| hospitalization | Hospitalization rates, if any, will be serially quantitated to trial completion | 3 months | 
| syncope hospitalization | syncope hospitalization rate quantitation to trial completion | 3 months | 
| liver function assay | serum liver function testing will be conducted at baseline and serially to trial completion | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
amiodarone, ranolazine, safety, arrhythmia