Ranolazine for Improving Symptoms of Palpitations

Study Overview
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Brief Summary
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Patients with ischemic heart disease often report multiple symptoms, including angina and palpitations. Ranolazine has antiarrhythmic effects which are largely a result of the drug's effect on multiple ion channels. It remains unknown, however, whether the favorable effects of ranolazine on symptoms and arrhythmias are maintained over time. Aim of this study is to test the hypothesis that chronic treatment with ranolazine can improve the symptomatic status of patients with ischemic heart disease by reducing the occurrence of palpitations.

Detailed Description
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Background: Patients with ischemic heart disease often report multiple symptoms, including angina and palpitations. Ranolazine is a novel antianginal and antiischemic drug that reduces intracellular sodium and calcium accumulation during ischemia thus limiting ischemic injury. Furthermore, ranolazine has antiarrhythmic effects which are largely a result of the drug's effect on multiple ion channels. It has previously been shown that treatment with ranolazine can reduce the frequency of supraventricular and ventricular tachycardia in the short term. In a subgroup analysis of the MERLIN-TIMI 36 trial, the continuous ECGs of 6,351 patients were analyzed. The results showed that, in comparison with placebo, treatment with ranolazine resulted in fewer episodes of ventricular tachycardia that lasted 8 beats or longer (5.3% versus 8.3%; P <0.001), and in fewer episodes of supraventricular tachycardia (44.7% versus 55%; P <0.001) and new-onset atrial fibrillation (1.7% versus 2.4%; P=0.08). It remains unknown, however, whether the favorable effects of ranolazine on symptoms and arrhythmias are maintained over time. Purpose: The primary objective of this study is to test the hypothesis that chronic treatment with ranolazine can improve the symptomatic status of patients with ischemic heart disease by reducing the occurrence of palpitations.

Official Title
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Ranolazine for the Treatment of sYmPtoms of PaLpitations in patiEnts With Ischemic Heart Disease - The RYPPLE Trial

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Drug: Ranolazine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Symptoms of palpitations Angiographically-proven coronary artery disease Stable conditions No recent acute coronary syndromes Able to understand and willing to sign the informed consent form Symptomatic patients (palpitation) with stable angina pectoris already on therapy with beta-blockers and/or calcium antagonists. Exclusion Criteria: Women of child bearing potential patients must demonstrate a negative pregnancy test performed within 24 hours Severe renal failure Severe hepatic failure
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ranolazine<br>Patients will receive ranolazine 750 mg bid for 30 days | Drug: Ranolazine<br>* os, pill, 750 mg, b.i.d., 30 days<br>* Other names: Ranexa TM, Gilead, US;|
| Placebo Comparator: Placebo<br>Patients will receive placebo for 30 days | Drug: Placebo<br>* os, pill, b.i.d., 30 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of symptoms of palpitations | Occurrence of symptoms of palpitations | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of arrhythmia in case of symptoms of palpitations | Definition of presence, number, type and duration of the arrhythmia in case of the patient-reported symptoms of palpitations | Up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Arrhythmias, palpitations