The Effect of Late Na Current Blocker Mexiletine on Giant T-wave Electrical Alternans(STOP-TWA)

Study Overview
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Brief Summary
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The electrocardiogram is one of the most basic tests for cardiovascular disease. T wave alternans (TWA), which reflects abnormal ventricular repolarization, can easily trigger ventricular tachycardia (VT) and ventricular fibrillation (VF), which are important warning clues for sudden cardiac death (SCD). The late sodium current (INaL) is an important component of the frequency-dependent regulation of cardiac repolarization, and various causes of delayed repolarization can increase INaL. Our study on long QT syndrome (LQTS) found that INaL abnormalities can lead to abnormal myocardial repolarization, producing a giant TWA that triggers VT and VF. VT and VF, and INaL inhibition by the INaL blocker mexilate can terminate this process. This suggests that pharmacological blockade of INaL may be a potential target for the prevention of SCD by ameliorating the different causes of giant TWA and its triggering ventricular arrhythmic events. In this study, we propose to randomize patients with VT/VF triggered by giant TWA to conventional treatment and conventional treatment adds mexiletine treatment to compare the effects of the two treatment regimens on giant TWA and its triggered nonsustained VT, sustained VT, and VF; at the same time, we will compare the effects of mexiletine on giant TWA and its triggered ventricular arrhythmias of various etiologies by intra-group control before and after treatment. The safety and efficacy of the treatment of TWA and its triggered ventricular arrhythmias are compared.

Official Title
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Potential of Late Na Current Blocker Mexilate on Giant T-wave Electrical Alternans and Subsequent Ventricular Arrhythmias: a Multicenter, Randomized, Prospective Study

Conditions
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Giant T-wave Electrical Alternans

Intervention / Treatment
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* Drug: Mexiletine
* Other: Conventional therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of macroscopic TWA Exclusion Criteria: The patients who do not agree to participate in the study, Patients with acute coronary syndrome or with progressive myocardial ischemia according to clinical manifestations, electrocardiogram or myocardial biochemical markers; Those who have used other class I antiarrhythmic drugs or who are contraindicated by mexiletine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Giant T-wave electrical alternans conventional plus mexiletine therapy<br>It is proposed that patients presenting with giant TWA-triggered VT/VF patients to be randomized to conventional treatment and conventional plus mexiletine treatment, respectively. | Drug: Mexiletine<br>* Mexiletine (150mg, bid, po) is given to patients who have been divided into Mexiletine group.<br>Other: Conventional therapy<br>* Treatment according to the guidelines for the management of ventricular arrhythmias (2017 AHA/ACC/HRS)<br>|
| Active Comparator: Giant T-wave electrical alternans conventional therapy<br>Conventional treatment in the control group according to the guidelines for the management of ventricular arrhythmias (2017 AHA/ACC/HRS) | Other: Conventional therapy<br>* Treatment according to the guidelines for the management of ventricular arrhythmias (2017 AHA/ACC/HRS)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 0 hour after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 24 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 48 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 72 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 96 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 120 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 144 hours after administration. | 
| The occurrence of macroscopic TWA | Macroscopic TWA occurring on conventional ECG (12-lead ECG, telemetry ECG, or holter ECG) with visually identifiable TWA Diagnosis confirmed by at least 3 leading ECG specialists. | within 168 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 0 hour after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 24 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 48 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 72 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 96 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 120 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 144 hours after administration. | 
| Termination of ventricular arrhythmias | Termination of Non-sustained ventricular tachycardia/sustained ventricular tachycardia/ventricular fibrillation. | within 168 hours after administration. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The related indicators of repolarization. | QT, Tp-e, QT/Tp-e, TDR, QRS | 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after administration. | 
| Length of hospital stay | Comparison between two treatment groups due to the effect of ventricular arrhythmia episodes on the duration of hospitalization ( days) in patients | 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after administration. | 
| Number of refractory cases | The number of cases in the group requiring ICD for ventricular arrhythmia episodes was used as an indicator. | 0 day, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days and 7 days after administration. |