Evaluation of Two Different Regimens of the Antiarrhythmic Drug Amiodarone to Maintain Normal Sinus Rhythm After Electrical Cardioversion in Patients With Persistent Atrial Fibrillation (PERIVERSION-2)

Multicenter Randomized Clinical Trial To Evaluate Two Different Amiodarone Regimens To Maintain Sinus Rhythm After Electrical Cardioversion In Persistent Atrial Fibrillation

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The goal of this clinical trial is to learn if reduced doses of amiodarone can treat atrial fibrillation (AF) effectively while minimizing toxic side effects in patients with persistent AF after electrical cardioversion. The main questions it aims to answer are:

• Can a reduced dose of amiodarone (100 mg/day) maintain sinus rhythm as effectively as the standard dose (200 mg/day) 12 months post electrical cardioversion?
• What are the adverse effects of the standard and reduced doses of amiodarone during 12 months post electrical cardioversion?
• How do genetic polymorphisms affect the efficacy and safety of amiodarone?
• How do amiodarone plasma levels correlate with the maintenance of sinus rhythm and genetic polymorphisms?

Researchers will compare the standard dose (200 mg/day) to the reduced dose (100 mg/day) to see if the reduced dose offers a better balance between efficacy and safety.

Participants will:

• Be treated with full dose amiodarone (200 mg/day) during the first month after electrical cardioversion.
• Be randomized to either continue with the full dose (200 mg/day) or switch to the reduced dose (100 mg/day).

The study is a multicenter, randomized clinical trial involving 312 patients with persistent AF after successful electrical cardioversion. Participants will be followed for 12-18 months to monitor the recurrence of AF and adverse effects.

Study Overview

• Status: Recruiting
• Conditions: Persistent Atrial Fibrillation
• Intervention / Treatment: Drug: Amiodarone Hydrochloride 200 MG; Drug: Amiodarone Hydrochloride 100 MG

• Study Type: Interventional
• Enrollment (Estimated): 312
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jose M Guerra, MD, PhD; Phone Number: +34 935565945; Email: jguerra@santpau.cat

Study Locations

• Spain
  • Barcelona, Spain, 08025
    • Recruiting
    • Hospital De La Santa Creu I Sant Pau
    • Contact: Jose M Guerra, MD, PhD; Phone Number: +34 935565945; Email: jguerra@santpau.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Patients aged ≥ 18 years
2. Documented persistent atrial fibrillation (≥ 7 days in duration)
3. Electively referred for Electrical Cardioversion
4. Signed informed consent.

Exclusion Criteria

1. Urgent electrical cardioversion
2. Atrial fibrillation post-cardiac surgery
3. Previous myocardial infarction
4. New York Heart Association (NYHA) Class IV heart failure
5. Left ventricular ejection fraction (LVEF) <45%
6. Significant left ventricular hypertrophy (wall thickness ≥ 15mm)
7. Hyperthyroidism or hypothyroidism
8. Known hepatobiliary disease (acute hepatitis, cirrhosis...) or ALT/AST > 3 x upper limit of normal (ULN)
9. Allergy, intolerance, or known hypersensitivity to study medications
10. Women of childbearing potential unwilling to use contraceptive measures and breastfeeding women.
11. Participation in another clinical trial involving investigational drugs
12. Life expectancy less than 12 months
13. Rheumatic mitral stenosis of any degree or severe mitral or aortic valve dysfunction.
14. Patients with contraindications to amiodarone, such as uncontrolled thyroid dysfunction, severe sinus bradycardia, second- or third-degree AV block without a pacemaker, and a history of amiodarone-induced pulmonary toxicity.
15. Patients in whom chronic amiodarone treatment previously failed to maintain sinus rhythm
16. Patients with abnormal baseline QTc (>450 ms in males and >470 in females) or abnormal ECG that precludes QTc assessment
17. Patients requiring concomitant medications that have a higher risk of QTc prolongation.
18. Patient do not have a smart mobile phone or do not know how to use it adequately.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Amiodarone full doses; Patients will receive amiodarone full doses (200 mg/day) (Usual dose)	Drug: Amiodarone Hydrochloride 200 MG; Patients will receive full amiodarone daily doses: 200 mg/day
Experimental: Amiodarone reduced doses; Patients will receive amiodarone reduced doses (100 mg/day)	Drug: Amiodarone Hydrochloride 100 MG; Patients will receive amiodarone reduced daily doses: 100 mg/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maintenance of sinus rhythm	Number of patients mantaining sinus rhythm 12 months post electrical cardioversion	12 months follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	12 months follow-up
Polymorphisms	Association of the different assessed polymorphisms with the primary and first secondary outcome	12 months follow-up
Plasma levels	Correlation of amiodarone plasma levels during follow-up with the maintenance of sinus rhythm	12 months follow-up

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma levels - polymorphisms	Correlation of amiodarone plasma levels with polymorphisms	12 month follow-up

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Collaborators: Instituto de Salud Carlos III

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Pharmacogenetics; Amiodarone; Adverse effects; Electrical cardioversion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzofurans; Amiodarone
• Other Study ID Numbers: IIBSP-AMI-2024-33; Project PI023/1768 (Other Grant/Funding Number: Instituto Salud Carlos III, Ministry of Science, Innovation and Universities, Government of Spain.); 2024-514113-35-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No