Efficacy of Varenicline Tartrate in Treating Frequent Premature Ventricular Contractions

Plain-language summary

This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial designed to evaluate the preliminary efficacy of varenicline tartrate in patients with frequent PVCs complicated by myocardial infarction (MI). The protocol was approved by the institutional review board and ethics committee at each participating center. Primary Efficacy Endpoint: 1\) The percentage change from baseline in the 24-hour mean count of PVCs at Week 6. Secondary Efficacy Endpoints: 1. The responder rate for PVCs at Weeks 4, 6, and 8. PVC responder: A participant is considered a responder if there is a ≥ 50% reduction from baseline in the 24-hour mean PVC count following treatment with either varenicline or placebo. 2. The incidence of NSVT from randomization through Weeks 4, 6, and 8. 3. The change from baseline in the 24-hour mean count and burden of PVCs at Weeks 4, 6, and 8. 4. The change from baseline in the 24-hour mean episodes and burden of non-sustained ventricular tachycardia (NSVT) at Weeks 4, 6, and 8. 5. The change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score at Week 6. Pre-specified Safety Endpoints: Primary Endpoint: The cumulative incidence of the first occurrence of malignant ventricular arrhythmias (time-to-first event), including sustained ventricular tachycardia (SVT), ventricular fibrillation (VF), or ventricular flutter (VFL), from randomization through Weeks 4, 6, and 8. Study Population: A total of 116 participants, aged 18-80 years, with frequent PVCs wil be enrolled. Prior to enrollment, participants must have stable cardiac conditions and must have received standard treatment for acute or chronic coronary syndrome as recommended by the relevant guidelines, including sustained-release metoprolol succinate. Following preliminary screening, participants will undergo 72-hour continuous three-lead AECG monitoring (baseline data) to assess the baseline PVC frequency. Eligibility for inclusion will be determined based on the monitoring data. Eligible participants will then be randomized in a 1:1 ratio (Day 0) to either the treatment group (varenicline tartrate tablets) or the placebo group. Treatment Protocol: All participants will receive sustained-release metoprolol succinate as part of the standard treatment, in accordance with clinical guidelines. The dose will remain stable throughout the study, unless adjustments are required for patient safety. Other standard treatments recommended by the guidelines, aside from sustained-release metoprolol succinate, will be optimized according to the clinical guidelines throughout the study. Randomization and Stratification: A total of 116 participants will be enrolled and randomized to either the treatment or placebo group, with 58 participants in each group. Stratification will be based on left ventricular ejection fraction (LVEF ≥ 50% vs. LVEF \< 50%). Treatment Regimen: Treatment Group (Varenicline Tartrate 0.5 mg/tablet): Participants will receive the following regimen: Days 1-3: 0.5 mg once daily. Days 4-42: 0.5 mg twice daily, taken at the same times each day (recommended interval 12 hours ± 2 hours). Days 43-45: 0.5 mg once daily. Placebo Group: Participants will receive placebo tablets according to the same regimen as the treatment group: Days 1-3: 1 tablet once daily. Days 4-42: 1 tablet twice daily, taken at the same times each day (recommended interval 12 hours ± 2 hours). Days 43-45: 1 tablet once daily. Statistical Analysis General Principles 1. Continuous (quantitative) variables: Summarized with n, mean, standard deviation, median, interquartile range, minimum, and maximum. 2. Categorical (count) variables: Presented as n (%). Unless otherwise specified, percentages will be calculated using the number of participants in the relevant analysis population as the denominator. Efficacy Analysis 1） Primary endpoint: The between-group difference will be assessed by estimating the mean difference in the percentage reduction from baseline in the 24-hour mean PVC count at Week 6, with 95% confidence intervals (CIs). Secondary endpoints: Two key secondary efficacy end points will be formally tested using a fixed-sequence (hierarchical) procedure. Key Secondary End Point 1: The responder rate for PVCs at Week 6. Key Secondary End Point 2: The incidence of NSVT at Week 6. All other secondary efficacy endpoints will be summarized descriptively. Safety Analysis The cumulative incidence of malignant ventricular arrhythmias will be estimated using Kaplan-Meier survival curves, with differences between groups compared using the Cox proportional hazards model (reporting the hazard ratio \[HR\] and 95% CI). If no events occur in either group or if the number of events is too low, only the number of events and their percentages will be reported.

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