NCT07519161

Pharmacological Intervention to Prevent NOAF After TAVR

Pharmacological Intervention for Atrial Arrhythmias to Prevent New-Onset Atrial Fibrillation After Transcatheter Aortic Valve Replacement: A Prospective, Multicenter, Randomized Controlled Trial

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 198 (estimated)
• Sponsor: Shanghai East Hospital · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to learn if amiodarone or metoprolol works to prevent new-onset atrial fibrillation (AF) in patients who develop certain atrial arrhythmias after transcatheter aortic valve replacement (TAVR). It will also learn about the safety of these drugs. The main questions it aims to answer are: * Do amiodarone or metoprolol reduce the incidence of new-onset AF within 90 days after TAVR? * What medical problems do participants have when taking amiodarone or metoprolol? Researchers will compare amiodarone and metoprolol to observation (no antiarrhythmic drug) to see if either drug reduces the development of new-onset AF. Participants who meet the post-TAVR arrhythmia criteria will: * Be randomly assigned to receive amiodarone, metoprolol, or observation * Take the assigned drug (if applicable) according to a specified dosing regimen * Be monitored continuously during hospitalization and undergo follow-up assessments at 30, 60, and 90 days, including ECGs, Holter monitors, and laboratory tests

Detailed description

Transcatheter aortic valve replacement (TAVR) is an established treatment for patients with symptomatic severe aortic stenosis. Although TAVR is less invasive than surgical valve replacement, post-procedural atrial arrhythmias-particularly atrial fibrillation (AF)-remain common and are associated with increased risks of stroke, heart failure, and mortality. Recent evidence suggests that a high burden of premature atrial contractions (PACs) and short episodes of atrial tachycardia (AT) occurring within the first days after TAVR may serve as precursors to new-onset AF (NOAF). However, the clinical significance of these early arrhythmias and the optimal management strategy are not well defined, and current guidelines lack consensus on the use of antiarrhythmic drugs (AADs) in this setting. This Phase 4, prospective, multicenter, randomized, open-label, parallel-group trial aims to determine whether early pharmacological intervention with either amiodarone (a class III AAD) or metoprolol (a beta-blocker) can reduce the incidence of NOAF within 90 days post-TAVR, compared with observation alone. A total of approximately 1383 patients undergoing TAVR across six centers in China will be screened. Patients who are in sinus rhythm pre-TAVR (confirmed by 24-hour Holter within 72 hours before the procedure) and who develop a high burden of atrial arrhythmias within the first 7 days after TAVR-defined as either ≥1,000 PACs per 24 hours or episodes of atrial tachycardia lasting 3-30 seconds-will be considered for randomization. Eligible patients are randomly assigned in a 1:1:1 ratio to one of three arms: (1) control (observation, no AAD initiated), (2) metoprolol succinate (starting at 47.5 mg once daily, with dose titration every 48 hours to achieve a target resting heart rate of 60-80 bpm), or (3) amiodarone (loading dose of 200 mg three times daily until a cumulative dose of 3 g is reached, followed by a maintenance dose of 200 mg once daily). Randomization is performed centrally using a computer-generated sequence, stratified by participating center. The study is open-label for participants and investigators, but endpoint adjudication (including the primary outcome) is performed by an independent outcomes assessor blinded to treatment allocation. All patients undergo continuous in-hospital telemetry after TAVR and wear an ambulatory ECG patch from intensive care unit admission onward, with data analyzed every 24 hours for up to 7 days. After randomization, patients are followed at 30, 60, and 90 days. At each follow-up visit, a 12-lead ECG, 72-hour Holter monitor, and laboratory tests (including complete blood count, liver and renal function, cardiac enzymes, BNP, electrolytes, thyroid function, and coagulation profile) are performed. A protocol-guided drug tapering and discontinuation strategy is implemented for the metoprolol and amiodarone groups. At each follow-up, if a patient demonstrates \<1,000 PACs per 24 hours and no atrial tachycardia on Holter, the drug dose is reduced by 50%. If the same criteria are met at the subsequent follow-up, the drug is discontinued. For safety, drug discontinuation is also mandated for symptomatic bradycardia (heart rate \<50 bpm or 50-60 bpm with syncope, dizziness, or fatigue), asymptomatic bradycardia (heart rate \<50 bpm), or ECG findings of PR interval \>200 ms, QT interval \>450 ms, or development of Mobitz type I second-degree AV block or higher. In the control and metoprolol groups, if a patient develops atrial flutter, atrial fibrillation, or an atrial tachycardia episode lasting \>30 seconds during follow-up, rescue therapy with amiodarone (or propafenone if amiodarone is contraindicated) is initiated. The primary outcome is the incidence of new-onset atrial fibrillation (NOAF) within 90 days post-randomization, defined as any documented AF episode lasting \>30 seconds on 12-lead ECG, telemetry, or Holter monitoring. Secondary outcomes include freedom from any atrial arrhythmia at 90 days (i.e., PACs \<1,000/24h, no atrial tachycardia, flutter, or fibrillation); a safety composite endpoint of high-degree atrioventricular block (HD-AVB: Mobitz type II second-degree AVB, third-degree AVB, or advanced AVB) or permanent pacemaker implantation; a clinical efficacy composite endpoint of all-cause mortality, stroke, or cardiovascular-related rehospitalization at 90 days; and the rate of permanent drug discontinuation due to adverse effects. Statistical analyses will be performed on an intention-to-treat population. The primary outcome will be compared among the three groups using the Chi-square test, with logistic regression to adjust for potential confounders. Time-to-first NOAF will be analyzed using Kaplan-Meier methods with log-rank test. A two-sided p-value \<0.05 is considered statistically significant. A Data Safety Monitoring Board will regularly review safety data, with particular attention to the rates of AV block and pacemaker implantation. The study is approved by the Institutional Review Board of Shanghai East Hospital (lead site) and will be conducted in accordance with the Declaration of Helsinki and ICH Good Clinical Practice guidelines. Written informed consent is obtained from all participants prior to any study-specific procedures. Results will be disseminated through peer-reviewed publications and presentations at international cardiology conferences.

Conditions

• Atrial Fibrillation

Interventions

Type	Name	Description
DRUG	Metoprolol succinate	Start: Metoprolol succinate 47.5 mg once daily (QD). Titration: Dose adjusted every 48 hours to achieve a target resting heart rate of 60-80 bpm.
DRUG	Amiodarone	Loading: 200 mg three times daily (TID) until a cumulative dose of 3g is reached. Maintenance: 200 mg QD thereafter.

Timeline

• Start date: 2026-04-07
• Primary completion: 2029-12-31
• Completion: 2030-03-31
• First posted: 2026-04-09
• Last updated: 2026-04-15