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)

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Status and phase: Enrolling; Phase 4

Conditions: Persistent Atrial Fibrillation

Treatments: Drug: Amiodarone Hydrochloride 200 MG; Drug: Amiodarone Hydrochloride 100 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT07273994

IIBSP-AMI-2024-33

2024-514113-35-00 (EU Trial (CTIS) Number)

Project PI023/1768 (Other Grant/Funding Number)

Details and patient eligibility

About

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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.

Enrollment: 312 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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312 participants in 2 patient groups

Amiodarone full doses

Active Comparator group

Description:

Patients will receive amiodarone full doses (200 mg/day) (Usual dose)

Treatment:

Drug: Amiodarone Hydrochloride 200 MG

Amiodarone reduced doses

Experimental group

Description:

Patients will receive amiodarone reduced doses (100 mg/day)

Treatment:

Drug: Amiodarone Hydrochloride 100 MG