Clinical trial NCT06645249: Evaluation of Cardioverter Capacity of Amiodarone Pre-electrical Cardioversion in Persistent Atrial Fibrillation
Official title: Multicenter, Randomized Clinical Trial to Evaluate the Cardioverter Capacity of Amiodarone Pre-electrical Cardioversion in Persistent Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Atrial Fibrillation (AF)
Keywords: Atrial fibrillation
Electrical cardioversion
amiodarone
Pharmacological cardioversion
Lead sponsor: Institut Investigacio Sanitaria Pere Virgili
Sponsor class: OTHER
Collaborators: name: Spanish Society of Cardiology
name: Sociedad Espanola de Cardiologia
First posted: 2024-10-16
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multicenter randomized phase IV open clinical trial. Patients with persistent AF (≥7 days duration) electively referred for CVE will be selected.

Two amiodarone regimens administered pre-CVE will be compared evaluating their cardioverter efficacy. Patients will be randomized to 2 groups:

c. Treatment impregnation with amiodarone starting one month before ECV (600 mg/day 1st week, 400 mg/day 2nd week and 200 mg/day thereafter until ECV).

d.Treatment impregnation with amiodarone 800 mg/day started 5 days before ECV.
Primary purpose: TREATMENT

Brief summary: Phase: IV Population: Sample size= 122 patients; male and female; ≥ 18 y.o.; patients with persistent atrial fibrillation referred for electrical cardioversion; performed in Spain Number of Sites: 4 Study Duration: 15/10/2024 - 15/5/2026 Subject Participation Duration: 2-4 months (depending on the arm) Description of Agent or Intervention: amiodarone

Objectives:

Primary: To compare the efficacy of amiodarone in pre-ECV reversal to sinus rhythm in a one-month impregnation regimen versus a 5-day regimen Secondary: 1) Identify days from initiation of pre-ECV amiodarone to reversion to SR using a mobile device paired to the mobile phone; 2) To compare the joint efficacy in the reversion to SR pre-ECV and in the maintenance of SR at 1 month after ECV of a one-month pre-ECV amiodarone impregnation regimen vs a 5-day regimen

Description of Study Design: Multicenter randomized open clinical trial. 122 Patients with persistent AF (≥7 days duration) electively referred for CVE will be included. Two amiodarone regimens administered pre-CVE will be compared evaluating their cardioverter efficacy. Patients will be randomized to 2 groups:

1. Treatment impregnation with amiodarone starting one month before ECV (600 mg/day 1st week, 400 mg/day 2nd week and 200 mg/day thereafter until ECV).
2. Treatment impregnation with amiodarone 800 mg/day started 5 days before ECV. Estimated Time to Complete Enrollment: 13 months

Detailed description: 4.3 RISK AND BENEFITS (if any) The study will compare two peri-ECV AAD regimens of amiodarone in the range of those recommended in the technical data sheet and label (16). For this reason, the risks of participation in the study would be equivalent to those present in standard clinical practice.

5. OBJECTIVES AND ENDPOINTS 5.1 OBJECTIVES: 5.1.1 Primary Objective i. To compare the efficacy of amiodarone in pre-ECV reversal to sinus rhythm in a one-month impregnation regimen versus a 5-day regimen 5.1.2 Secondary Objectives i. Identify days from initiation of pre-ECV amiodarone to reversion to SR using a mobile device paired to the mobile phone.

ii. To compare the joint efficacy in the reversion to SR pre-ECV and in the maintenance of SR at 1 month after ECV of a one-month pre-ECV amiodarone impregnation regimen vs a 5-day regimen 5.2 ENDPOINTS 5.2.1 Endpoint (s) for the primary objective i. Reversal to sinus rhythm pre-ECV (number of patients) 5.2.2 Endpoint (s) for the secondary objectives i. Days until reversal to sinus rhythm ii. Maintenance of sinus rhythm at 1 month after cardioversion 5.3 HYPOTHESIS:

1. In patients with persistent AF referred to ECV, a long amiodarone impregnation regimen (one month pre-CVE) would induce pharmacological cardioversion in about a fifth of patients and would be superior to a short impregnation regimen (5 days).
2. Reversal to SR induced by the administration of pre-CVE amiodarone may occur in a vulnerable period for embolic events in patients in whom OAC is initiated pre-CVE. The use of a device that monitors the ECG daily will be useful to know when the reversion to pre-CVE RS occurs.
3. The proportion of patients who maintain the SR at one month post-CVE will be similar in a long regimen vs. a short regimen of pre-CVE amiodarone.

6. STUDY DESIGN This is a multicenter randomized phase IV open clinical trial. Patients with persistent AF (≥7 days duration) electively referred for CVE will be selected. After verifying that they meet the inclusion and exclusion criteria, candidates will be invited to participate in the study. Patients will receive information about the study and those who agree to participate will sign the informed consent.

Two amiodarone regimens administered pre-CVE will be compared evaluating their cardioverter efficacy. Patients will be randomized to 2 groups:

c. Treatment impregnation with amiodarone starting one month before ECV (600 mg/day 1st week, 400 mg/day 2nd week and 200 mg/day thereafter until ECV).

d. Treatment impregnation with amiodarone 800 mg/day started 5 days before ECV. Patients who do not revert to SR pre-ECV will be treated with ECV. Those who have pharmacologically reverted to SR or who have had a successful CVE will be treated with amiodarone 200 mg/day after restoration of SR. A one-month follow-up will be carried post-ECV to evaluate the maintenance of SR. ECV will be carried out as per standard clinical practice with 200 J biphasic energy and, if ineffective, maximum energy will be used.

According to the ESC clinical practice guidelines for AF, adequate anticoagulation is a necessary requirement for at least 3 weeks before ECV to avoid the risk of embolism associated with cardioversion. Patients on chronic anticoagulation will be started on the assigned pre-ECV amiodarone regimen after inclusion. Patients who are not already receiving anticoagulant treatment will begin anticoagulant treatment with direct anticoagulants. In this case, they will wait 3 weeks before starting the amiodarone regimen to avoid the risk of embolism during this period.

At baseline visit, the patient will be given a mobile electrocardiographic monitoring device to determine which patients revert to SR and the time of reversal. Patients will record a daily pre-ECV ECG strip that will be transmitted to the investigator team of each participating center. During the post-ECV follow-up month, patients will send a weekly ECG via the mobile monitoring device. During clinical visits a physical examination, ECG, vital signs, blood samples collection, record of concomitant medication and collection of adverse events will be performed.

No other AADs (except beta-blockers or calcium antagonists) will be allowed during the study. Patients who experience recurrence of AF or adverse side effects will be discontinued from the study.

Eligibility criteria: Inclusion Criteria:

1. Patients ≥18 years old.
2. Persistent atrial fibrillation (≥ 7 days duration).
3. Referred for elective electrical cardioversion.
4. Signing of the informed consent

Exclusion Criteria:

1. Need of urgent electrical cardioversion
2. Mean Heart rate \&lt;50 bpm
3. Planned ablation \&lt; 1 month after ECV.
4. Treatment with anti-arrhythmic drugs (IC, III) the last 7 days previous to inclusion (in the case of amiodarone on the 30 days previous to inclusion)
5. Atrial fibrillation post-cardiac surgery
6. New York Heart Association (NYHA) Class IV heart failure
7. Left ventricular ejection fraction (LVEF) ≤30%
8. History of thyroid disease (hyperthyroidism or hypothyroidism)
9. Known hepatobiliary disease (acute hepatitis, cirrhosis...) or ALT/AST \&gt; 3 x upper limit of normal (ULN)
10. Allergy, intolerance, or known hypersensitivity to study medication
11. Women of childbearing potential unwilling to use contraceptive measures
12. Participation in another clinical trial involving investigational drugs
13. Life expectancy less than 12 months
14. Rheumatic mitral stenosis of any degree or severe mitral or aortic valve dysfunction.

Primary outcomes:
measure: Reversal to sinus rhythm pre-electrical cardioversion
timeFrame: From date of enrollment until the date of electrical cardioversion, up to 8 weeks
Secondary outcomes:
measure: Days until reversal to sinus rhythm
timeFrame: From date of enrollment until date of electrical cardioversion, up to 8 weeks
measure: Maintenance of sinus rhythm at 1 month after cardioversion
timeFrame: From date of reversion to sinus rhythm until 1 month later
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Reus
country: Spain
facility: Hospital Universitari de Sant Joan
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago
Study officials:
References: