Effect of Prolonged Use of Dronedarone on Recurrence in Patients With Non-paroxysmal Atrial Fibrillation After Radiofrequency Ablation (DORIS)

Recurrence rate remains high after radiofrequency ablation in patients with non-paroxysmal atrial fibrillation(AF). Prolonged use of anti-arrhythmic drugs (AAD) beyond the post-ablation blanking has been adopted as a solution but without sufficient clinical evidence. Dronedarone is an AAD valid to maintain sinus rhythm and has fewer side effect than other AAD for long-term use.We sought to investigate the effect of prolonged use of dronedarone on recurrence of non-paroxysmal AF patients beyond the post-blanking period within the first year after ablation.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Dronedarone; Drug: Placebo

Detailed Description

In this multicenter, randomized, placebo-controlled trial, patients with non-paroxysmal AF will receive dronedarone for three months after radiofrequency ablation. Eligible Patients will then be randomly divided into dronedarone and placebo groups and followed up until one year after ablation. The primary endpoint is the cumulative nonrecurrence rate post three months and within one year after ablation. 7-day Holter monitoring (ECG patch) will be scheduled at 6,9, and 12 months after ablation for evaluating AA recurrence. Secondary endpoints include dronedarone withdrawal due to side effect or intolerance of AA recurrence, time to the first recurrence, repeat ablation, electrical cardioversion, unscheduled visit ,and rehospitalization.

This trial will evaluate whether prolonged use of dronedarone effectively reduces recurrence rate after ablation in non-paroxysmal AF patients. The result of this trial will provide evidence for optimizing post-ablation anti-arrhythmic therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 268
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Shanghai East Hospital
    • Contact: Bing Yang, MD; Phone Number: +86-18117141291; Email: ybheart@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-80 years;
2. Diagnosis of non-paroxysmal AF
3. Undergoing AF ablation for the first time

Exclusion Criteria:

1. Unwilling to take or intolerant to dronedarone;
2. Hypersensitivity to the drug ingredient
3. Patients with decompensated heart failure, class NYHA IV, or left ventricular ejection fraction (LVEF) ≤40%
4. Bradycardia <50 bpm
5. QTc Bazett interval ≥500ms or PR interval >280ms
6. II or III atrioventricular (AV) block or sick-sinus syndrome without permanent pacemaker
7. Diagnosed with acute coronary syndrome or treated with percutaneous coronary intervention within the last 3 months
8. Patients with structural heart disease (moderate to severe aortic or mitral valve stenosis, interventricular septal thickness >15mm, congenital heart disease)
9. Accepted cardiac surgery within the last 3 months
10. Left atrial diameter (LAD) >55 mm
11. Patients with left atrial or left auricular thrombosis
12. Patients with Hyperthyroidism
13. Severe dysfunction of liver and kidney diseases (ALT≥3ULN or eGFR<30ml/min/1.73m2)
14. Abnormal blood coagulation
15. Concomitant use of dabigatran
16. Concomitant use of drugs that prolong QTc or may induce torsades de pointes
17. Concomitant use of strong CYP3A inhibitors
18. Concomitant use of another Class IA, IC, or III AADs
19. Patients suffering from serious infection, mental illness or malignant tumors
20. Pregnancy or breast-feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: dronedarone; dronedarone 400mg twice a day for 9 months	Drug: Dronedarone; oral administration fed conditions
Placebo Comparator: placebo; Placebo(for dronedarone ) a day for 9 months	Drug: Placebo; strictly identical in appearance with dronedarone,oral administration fed conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cumulative nonrecurrence rate	defined as any atrial tachyarrhythmias (including atrial fibrillation, atrial flutter, or atrial tachycardia) recorded by electrocardiogram (ECG)>30s	post 3 to 12 months after ablation

Secondary Outcome Measures

Outcome Measure	Time Frame
time to first recurrence	post 3 to 12 months after ablation
cardioversion due to recurrence	post 3 to 12 months after ablation
repeat ablation due to recurrence	post 3 to 12 months after ablation
unscheduled visit and rehospitalization due to recurrence	post 3 to 12 months after ablation
drug withdrawal because of side effect	post 3 to 12 months after ablation
drug withdrawal due to intolerance to or persistent AA(lasting more than 7 days)	post 3 to 12 months after ablation

Collaborators and Investigators

• Sponsor: Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): November 1, 2025

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 19, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 11, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: placebo; ablation; dronedarone; non-paroxysmal atrial fibrillation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Recurrence; Anti-Arrhythmia Agents; Dronedarone
• Other Study ID Numbers: DFLC2022011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No