Efficacy and Safety of memanTine in the Treatment Of Frequently symPtomatic Atrial Premature Beats

Not Applicable

Not yet recruiting

• Conditions: Atrial Premature Beats, Contractions, or Systoles
• Interventions: Drug: Memantine Hydrochloride 10 MG; Drug: Placebo

• Registration Number: NCT06501638
• Lead Sponsor: Shanghai East Hospital

Brief Summary

A multicenter, randomized, double-blind, placebo-controlled study to expIore the efficacy and safety of Memantine hydrochIoride tabIets to treat patients with frequent PACs.

Detailed Description

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 amiodarone 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 amiodarone 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.

Study Timeline

• Status Verified: 2024-07
• Study Start: 2024-07-07
• Study First Submitted: 2024-07-09
• Study First Submitted QC: 2024-07-09
• Study First Posted: 2024-07-15
• Last Update Submitted: 2024-07-16
• Last Update Posted: 2024-07-18
• Primary Completion: 2025-07-07
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 256

Inclusion Criteria

1. Age between 18 and 80 (inclusive).
2. Presence of symptoms related to premature atrial contractions (PACs) during screening, with PACs occurring ≥1000 times/24 hours.
3. Understanding and willingness to comply with the study procedures and methods, voluntary participation in the study, and signing an informed consent form.

Exclusion Criteria

1. Presence of atrial fibrillation, atrial flutter, sustained atrial tachycardia (confirmed by electrocardiogram within the past 6 months or continuous 3-day (72 hours) holter patch monitoring at baseline), or frequent ventricular premature contractions (confirmed by electrocardiogram within the past 6 months or continuous 3-day (72 hours) holter patch monitoring at baseline with ventricular premature contractions ≥1000 times/24 hours), ventricular tachycardia (excluding occasional short episodes during sleep), or ventricular fibrillation.
2. 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 cardiac radiofrequency ablation within the past 6 months prior to screening.
3. Left ventricular ejection fraction (LVEF) ≤40%; or New York Heart Association (NYHA) functional class III or IV; or left atrial diameter ≥55mm.
4. Sick sinus syndrome, second-degree type II or higher atrioventricular block, or bifascicular block without permanent pacemaker implantation; or confirmed coexistence of systemic or metabolic diseases that may cause severe bradycardia or conduction abnormalities, such as cardiac sarcoidosis or untreated severe hypothyroidism.
5. 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 2 weeks prior to screening.
6. 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 cardiomyopathy, congenital long QT syndrome, congenital short QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia.
7. Coexistence of other diseases with an expected survival period of less than 1 year.
8. Active hepatitis or significant liver dysfunction (ALT or AST >3 times the upper limit of normal [ULN], TBIL >3 ULN).
9. Severe renal insufficiency (calculated estimated glomerular filtration rate [eGFR] <40 ml/min/1.73m² using the CKD-EPI equation).
10. 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).
11. Pregnancy, lactating women, or positive pregnancy test result before randomization.
12. Presence of potentially reversible causes of premature atrial contractions, such as hyperthyroidism, cardiac thoracic surgery, electrolyte disturbances, etc. Premature contractions decrease and symptoms significantly improve after removing the triggers (such as alcohol abuse, acute exacerbation of chronic obstructive pulmonary disease [AECOPD] with respiratory failure or uncorrected infection, etc.).
13. History of epilepsy, seizures, or mental illness.
14. Known allergy to memantine hydrochloride tablets or their excipients.
15. Patients currently receiving memantine treatment for moderate or severe Alzheimer's disease.
16. Other circumstances where the investigator deems the subject unsuitable for inclusion in the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Memantine	Memantine Hydrochloride 10 MG	Take Memantine Hydrochloride for intervention
Placebo	Placebo	Take placebo for intervention

Primary Outcome Measures

Name	Time	Method
percentage reduction of 24-hour premature atrial beats count	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)

Secondary Outcome Measures

Name	Time	Method
change of 24-hour premature atrial beats count	The fourth, sixth and eighth 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.; change of 24-hour premature atrial beats count =24-hour premature atrial beats count(baseline)-24-hour premature atrial beats count (observation time)
change of 24-hour premature atrial beats burden	The fourth, sixth and eighth 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 burden was then calculated.; change of 24-hour premature atrial beats burden =24-hour premature atrial beats burden(baseline)-24-hour premature atrial beats burden (observation time)
change of 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation burden	The fourth, sixth and eighth week after intervention	Participants accepted 3-day holter patch monitor at baseline, fourth, sixth and eighth week after intervention. Average sustained atrial tachycardia, atrial flutter and atrial fibrillation burden was then calculated.; change of 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation burden=newly discovered 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation burden (observation time)
change of 24-hour non-sustained atrial tachycardia episodes	The fourth, sixth and eighth 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 episodes was then calculated.; change of 24-hour non-sustained atrial tachycardia episodes=24-hour non-sustained atrial tachycardia episodes (baseline)- 24-hour non-sustained atrial tachycardia episodes (observation time)
change of 24-hour non-sustained atrial tachycardia burden	The fourth, sixth and eighth week after intervention	Participants accepted 3-day holter patch monitor at baseline, fourth, sixth and eighth week after intervention. Average 24-hour non-sustained atrial tachycardia burden was then calculated.; change of 24-hour non-sustained atrial tachycardia burden =24-hour non-sustained atrial tachycardia burden(baseline)- 24-hour non-sustained atrial tachycardia burden (observation time)
change of 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation episodes	The fourth, sixth and eighth week after intervention	Participants accepted 3-day holter patch monitor at baseline, fourth, sixth and eighth week after intervention. Average 24-hour sustained atrial tachycardia, atrial flutter and atrial fibrillation episodes was then calculated.; change of 24-hour non-sustained atrial tachycardia episodes=newly discovered 24-hour non-sustained atrial tachycardia episodes (observation time)
SF-36 score change	The sixth week after intervention	Participants accepted the Mos 36-item Short Form Health Survey evaluation at baseline and sixth after intervention.; SF-36 score change= SF-36 score (baseline)-SF-36 score (sixth week)

Trial Locations

Locations (1)

Shanghai East hospital; 🇨🇳 Shanghai, Shanghai, China