Multicenter randomized clinical trial to evaluate two different amiodarone regimens to maintain sinus rhythm after cardioversion in persistent atrial fibrillation (PERIVERSION-2).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Nov 2025 → ongoing

Decision date (initial)

2025-01-27

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To compare the efficacy in maintaining sinus rhythm 12 months post electrical cardioversion between standard (200 mg/d) and reduced (100 mg/d) doses of amiodarone in patients with persistent atrial fibrillation.

Secondary objectives 4

1. To compare the adverse effects of standard (200 mg/d) and reduced (100 mg/d) doses of amiodarone during 12 months post electrical cardioversion in patients with persistent atrial fibrillation. The response criterion for safety will be the presence or absence of major adverse events, such as thyroid, liver or lung toxicity.
2. Evaluate the efficacy and safety of amiodarone based on polymorphisms in CYP2D6, CYP2C19, CYP1A2, CYP2C8, CYP3A4, and ABCB1.
3. Correlate amiodarone plasma levels with the maintenance of sinus rhythm at 12 months post cardioversion.
4. Correlate amiodarone plasma levels with polymorphisms in CYP2D6, CYP2C19, CYP1A2, CYP2C8, CYP3A4, and ABCB1.

Conditions and MedDRA coding

Persistent atrial fibrillation

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

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

Exclusion criteria 14

1. Urgent electrical cardioversion
2. Women of childbearing potential unwilling to use contraceptive measures and breastfeeding women.
3. Participation in another clinical trial involving investigational drugs
4. Life expectancy less than 12 months
5. Rheumatic mitral stenosis of any degree or severe mitral or aortic valve dysfunction.
6. Atrial fibrillation post-cardiac surgery
7. Previous myocardial infarction
8. New York Heart Association (NYHA) Class IV heart failure
9. Left ventricular ejection fraction (LVEF) <45%
10. Significant left ventricular hypertrophy (wall thickness ≥ 15mm)
11. Hyperthyroidism or hypothyroidism
12. Known hepatobiliary disease (acute hepatitis, cirrhosis...) or ALT/AST > 3 x upper limit of normal (ULN)
13. Allergy, intolerance, or known hypersensitivity to study medications
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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. First recurrence of AF (requires ECG) after randomization.

Secondary endpoints 4

1. Assessment of adverse effects, which will be determined by specific criteria including TSH levels below 0.1 microUI/ml, TSH levels exceeding 4.2 microUI/ml, a threefold increase in AST, ALT, or GGT compared to baseline levels, a QTc interval exceeding 500 ms or any other adverse effects as per the drug technical sheet.
2. Study of polymorphisms in CYP2D6, CYP2C19, CYP1A2, CYP2C8, CYP3A4, and ABCB1.
3. Plasma levels of amiodarone during follow-up
4. Correlate polymorphisms, with plasma levels, safety and efficacy.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Sponsor organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Address

Calle De San Quintin 77-79

City

Barcelona

Postcode

08041

Country

Spain

Scientific contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC Sant Pau

Public contact point

Organisation

Fundacio Institut De Recerca De L Hospital De La Santa Creu I Sant Pau

Contact name

UICEC Sant Pau

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications