Efficacy and Safety of memanTine in the Treatment Of Frequently symPtomatic Atrial Premature Beats: a Multicenter Randomized Double-blind Placebo-controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 256
- 试验地点
- 1
- 主要终点
- percentage reduction of 24-hour premature atrial beats count
研究概览
简要总结
A multicenter, randomized, double-blind, placebo-controlled study to expIore the efficacy and safety of Memantine hydrochIoride tabIets to treat patients with frequent PACs.
详细描述
After preliminary screening, the target patients will undergo continuous 3-day (72-hour) monitoring with a wearable holter patch(as baseline data) to assess the number of baseline atrial premature beats. Based on the monitored data, it will be determined whether the subjects meet the inclusion criteria. Eligible participants will be randomly assigned in a 1:1 ratio (on Day 0) to either the experimental group (administered with hydrochloride memantine tablets) or the control group (placebo). A total of 256 subjects will be enrolled, with 128 subjects in each group, stratified by age (age ≥ 65 years vs. age < 65 years) and the number of atrial premature beats (≥ 5000 beats/24h vs. < 5000 beats/24h).
The subjects in the experimental group will take hydrochloride memantine tablets according to the following regimen:Week 1: Half tablet per dose (5mg/dose), twice daily, taken orally at the same time in the morning and evening (with a recommended dosing interval of 12 hours ± 2 hours).Week 2 to Week 6: One tablet per dose (10mg/dose), twice daily, taken orally at the same time in the morning and evening (with a recommended dosing interval of 12 hours ± 2 hours).
Control group (placebo): The subjects in the control group will take placebo according to the following regimen:Week 1: Half tablet per dose, twice daily, taken orally at the same time in the morning and evening (with a recommended dosing interval of 12 hours ± 2 hours).Week 2 to Week 6: One tablet per dose, twice daily, taken orally at the same time in the morning and evening (with a recommended dosing interval of 12 hours ± 2 hours).
The study consists of a screening period (D0-D7 days), a treatment period (D8-D42 days), and a follow-up period (D43-D56 days).The start dates for the 3-day ambulatory holter patch are as follows: D25-D28, D39-D42, and D53-D56.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 18 and 80 (inclusive).
- •Presence of symptoms related to premature atrial contractions (PACs) during screening, with PACs occurring ≥1000 times/24 hours.
- •Understanding and willingness to comply with the study procedures and methods, voluntary participation in the study, and signing an informed consent form.
排除标准
- •Atrial fibrillation, atrial flutter, or persistent atrial tachycardia (confirmed by electrocardiogram within the past 6 months or detected by continuous 3-day (72h) monitoring with a wearable Holter monitor at baseline); or ventricular tachycardia (excluding occasional short episodes of ventricular tachycardia during sleep) or ventricular fibrillation.
- •Occurrence of a stroke event, including hemorrhagic/ischemic stroke and transient ischemic attack (TIA), within the past 6 months prior to screening; history of cardiac surgery, myocardial infarction (MI), percutaneous coronary intervention (PCI), or atrial arrhythmia radiofrequency ablation within the past 3 months prior to screening.
- •Left ventricular ejection fraction (LVEF) ≤40%; or New York Heart Association (NYHA) functional class III or IV.
- •Sick sinus syndrome, second-degree type II or higher atrioventricular block, or bifascicular block without permanent pacemaker implantation.
- •Ongoing use of amiodarone within the past 4 weeks prior to screening, or ongoing use of antiarrhythmic drugs other than amiodarone, as well as Chinese herbal medicine with antiarrhythmic effects within the past 1 weeks prior to screening.
- •Presence of unstable angina, severe congenital heart disease (excluding patent foramen ovale), post-artificial heart valve replacement, acute myocarditis, acute endocarditis, rheumatic heart valve disease,Hypertrophic obstructive cardiomyopathy.
- •Coexistence of other diseases with an expected survival period of less than 1 year.
- •Active hepatitis or significant liver dysfunction (ALT or AST >3 times the upper limit of normal [ULN], TBIL >3 ULN).
- •Severe renal insufficiency (calculated estimated glomerular filtration rate [eGFR] <40 ml/min/1.73m² using the CKD-EPI equation).
- •Received investigational drugs or medical device treatments in other clinical trials within 1 month prior to screening or within 5 half-lives (whichever is longer).
- •Pregnancy, lactating women, or positive pregnancy test result before randomization.
- •Hyperthyroidism that has not been properly treated and thyroid function has not returned to normal, the perioperative period of cardiothoracic surgery (one week before surgery to two weeks after surgery), uncorrected electrolyte disturbances (serum K+ > 5.5 mmol/L or < 3.5 mmol/L, serum magnesium < 1.5 mmol/L, etc.); chronic obstructive pulmonary disease (COPD) combined with respiratory failure or infection that has not been corrected, etc.
- •History of epilepsy, seizures, or mental illness.
- •Known allergy to memantine hydrochloride tablets or their excipients.
- •Patients currently receiving memantine treatment for moderate or severe Alzheimer's disease.
- •Other circumstances where the investigator deems the subject unsuitable for inclusion in the study.
研究组 & 干预措施
Memantine
Take Memantine Hydrochloride for intervention
干预措施: Memantine Hydrochloride 10 MG (Drug)
Placebo
Take placebo for intervention
干预措施: Placebo (Drug)
结局指标
主要结局
percentage reduction of 24-hour premature atrial beats count
时间窗: The sixth week after intervention
Participants accepted 3-day holter patch monitor at baseline, fourth, sixth and eighth week after intervention. Average 24-hour premature atrial beats count was then calculated. percentage reduction of 24-hour premature atrial beats count = (24-hour premature atrial beats count(baseline)-24-hour premature atrial beats count (sixth week) ) /24-hour premature atrial beats count(baseline)
次要结局
- change of 24-hour premature atrial beats count(The fourth, sixth and eighth week after intervention)
- change of 24-hour premature atrial beats burden(The fourth, sixth and eighth week after intervention)
- change of 24-hour non-sustained atrial tachycardia episodes(The fourth, sixth and eighth week after intervention)
- change of 24-hour non-sustained atrial tachycardia burden(The fourth, sixth and eighth week after intervention)
- change of 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation episodes(The fourth, sixth and eighth week after intervention)
- The proportion of new-onset persistent atrial tachycardia, atrial fibrillation (AF), and atrial flutter during continuous 72-hour monitoring at weeks 4, 6, and 8(The fourth, sixth and eighth week after intervention)
- Cumulative incidence of new-onset AF from week 0 to week 8:(The eighth week after intervention)
- SF-36 score change(The sixth week after intervention)
- Efficacy analysis of atrial premature beats or non-sustained atrial tachycardia(The fourth, sixth and eighth week after intervention)
- Safety profile of memantine in patients with frequent symptomatic PACs(The eighth week after intervention)
研究者
Yihan Chen
Professor
Shanghai East Hospital