Prevention of New Onset AF After TAVI (PAF-TAVI Trial)

Study Overview
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Brief Summary
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New onset atrial fibrillation (NOAF) is a relatively frequent complication after transcatheter aortic valve implantation (TAVI). This complication has been related with worse short and long-term outcomes, including higher stroke, mortality, readmission and bleeding rates. The aim of this study is to evaluate the effectiveness of amiodarone in the prevention of the NOAF after TAVI. The study is a multicenter, randomized double-blinded trial including 120 patients without prior AF that will undergo TAVI in a scheduled basis. Patients will be randomized to be treated with amiodarone orally from 6 days before to 6 days after the TAVI procedure versus placebo. All the patients will be monitored with a 60-day holter to evaluate NOAF incidence. The main objective is NOAF incidence after TAVI at 30-day. Secondary endpoints are the incidence of NOAF, stroke, bleeding and all-cause and cardiovascular mortality in both groups at 60-day. Results of this study can contribute to optimize TAVI results in a short and long term, potentially improving the survival and quality of life in this group of frail patients with comorbidities, which makes them vulnerable to NOAF, stroke, bleeding, heart failure and readmission.

Official Title
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Usefulness of Amiodarone for the Prevention of New Onset Atrial Fibrillation After Transcatheter Aortic Valve Implantation: a Randomized Controlled Trial

Conditions
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Atrial Fibrillation New Onset

Intervention / Treatment
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* Procedure: transcatheter aortic valve implantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women over 18 years old. Women of childbearing age must commit to the use of contraceptive methods of assured efficacy. Patients that will undergo TAVI due to aortic stenosis. Sinus rhythm showed by an ECG during 72 hours previous to the inclusion in the study. Exclusion Criteria: Pregnancy or lactation. Women of childbearing age who do not have a negative pregnancy test. Paroxysmal persistent or persistent AF (documented record in electrocardiogram or ECG holter) Congestive heart failure with functional class NYHA IV despite optimal medical treatment. Sustained hypotension (TAS < 80mmHg) Severe mitral stenosis or regurgitation Treatment with antiarrhythmic drugs (amiodarone included) 3 months before the procedure, treatment with beta-blockers or dihydropyrimidine calcium channel blockers are not considered an exclusion criteria. Sinus bradycardia (< 50 lpm), PR interval >240 mseg or second or third degree AV block. QT interval longer than 480 msec in an EKG performed in 72 hours before the inclusion, without a permanent pacemaker. Clinical hypo- or hyperthyroidism, clinical or subclinical autoimmune thyroid disease, or multinodular goiter. Allergy or adverse reaction known or suspected to the amiodarone. Denial of the patient or inability to give informed consent. Hypersensitivity to iodo Concomitant drugs that, in association with amiodarone, can induce torsades de pointes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase III Clinical trial, multiple sites, controlled, randomized, double blind, parallel groups.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiodarone<br>Oral Amiodarone 600mg / day, divided into 3 doses (200mg every 8 hours) for 6 days before the procedure and then 400mg / day, divided into 2 doses (200mg every 12 hours) during the 6 days following the implantation of TAVI. | Procedure: transcatheter aortic valve implantation<br>* transcatheter aortic valve implantation<br>|
| Placebo Comparator: Control<br>Patients assigned to the control group will receive placebo tablets identical to those of amiodarone. The administration of these tablets will follow the same scheme as in the amiodarone group. Therefore, they will receive placebo tablets orally, 1 tablet every 8 hours 6 days before the procedure and then 1 tablet every 12 hours during the 6 days following the implantation of TAVI | Procedure: transcatheter aortic valve implantation<br>* transcatheter aortic valve implantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new onset atrial fibrillation | Compare the incidence of new onset atrial fibrillation (NOAF) on patients that receive oral amiodarone versus placebo. NOAF is defined as an irregular rhythm without P wave and irregular ventricular response during at least 30 seconds, detected in the electrocardiographic monitoring during the post-procedural period or in the 60 days ECG Holter in a patient without previous history of atrial fibrillation. NOAF incidence within 30-day after the TAVI procedure is the primary end-point. | 30 days after transcatheter aortic valve implantation (TAVI) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of new onset atrial fibrillation | Compare the incidence of new onset atrial fibrillation (NOAF) on patients that receive oral amiodarone versus placebo. NOAF is defined as an irregular rhythm without P wave and irregular ventricular response during at least 30 seconds, detected in the electrocardiographic monitoring during the post-procedural period or in the 60 days ECG Holter in a patient without previous history of atrial fibrillation. NOAF incidence within 30-day after the TAVI procedure is the primary end-point. | 60 days after transcatheter aortic valve implantation (TAVI) | 
| Effect of the amiodarone | Analyze the effect of the amiodarone in the moment of appearance and the burden of AF after TAVI. AF burden, defined as the relative length of the AF registers in relation to the time in sinus rhythm. | 1-year follow-up | 
| Mortality and CV mortality. | Compare all-cause mortality and CV mortality between groups. | 1-year follow-up | 
| Number of parients with MACE | MACE: Stroke, bleeding (major or life-threatening), and all-cause and cardiovascular mortality rate. | at 30 days after NOAF | 
| Number of parients with MACE | MACE: Stroke, bleeding (major or life-threatening), and all-cause and cardiovascular mortality rate. | at 60 days after NOAF | 
| Number of parients with MACE | MACE: Stroke, bleeding (major or life-threatening), and all-cause and cardiovascular mortality rate. | at 6 months after NOAF | 
| Number of parients with MACE | MACE: Stroke, bleeding (major or life-threatening), and all-cause and cardiovascular mortality rate. | 1-year follow-up | 
| Number of adverse events related to amiodarone | The safety evaluation will be realized by a meticulous vigilance of the adverse effects appeared in the study population. | at 30 days after NOAF | 
| Number of adverse events related to amiodarone | The safety evaluation will be realized by a meticulous vigilance of the adverse effects appeared in the study population. | at 60 days after NOAF | 
| Number of adverse events related to amiodarone | The safety evaluation will be realized by a meticulous vigilance of the adverse effects appeared in the study population. | at 6 months after NOAF | 
| Number of adverse events related to amiodarone | The safety evaluation will be realized by a meticulous vigilance of the adverse effects appeared in the study population. | 1-year follow-up | 
| Incidence of permanent pacemaker implantation in the both groups. | Need of permanent pacemaker implantation in the both groups. | at 30 days after NOAF | 
| Incidence of permanent pacemaker implantation in the both groups. | Need of permanent pacemaker implantation in the both groups. | at 60 days after NOAF | 
| Incidence of permanent pacemaker implantation in the both groups. | Need of permanent pacemaker implantation in the both groups. | at 6 months after NOAF | 
| Incidence of permanent pacemaker implantation in the both groups. | Need of permanent pacemaker implantation in the both groups. | 1-year follow-up | 
| Quality of life: EuroQoL 5D | Eq-5D: EuroQoL 5 Dimensions. Score between 0 and 1. The best score 1. | at 30 days after NOA | 
| Quality of life: Kansas City test | Score between 0 and 100. The best score 100. | at 30 days after NOA | 
| Quality of life: EuroQoL 5D | Eq-5D: EuroQoL 5 Dimensions. Score between 0 and 1. The best score 1. | at 60 days after NOAF | 
| Quality of life: Kansas City test | Score between 0 and 100. The best score 100. | at 60 days after NOAF | 
| Quality of life: EuroQoL 5D | Eq-5D: EuroQoL 5 Dimensions. Score between 0 and 1. The best score 1. | at 6 months after NOAF | 
| Quality of life: Kansas City test | Score between 0 and 100. The best score 100. | at 6 months after NOAF | 
| Quality of life: EuroQoL 5D | Eq-5D: EuroQoL 5 Dimensions. Score between 0 and 1. The best score 1. | 1-year follow-up | 
| Quality of life: Kansas City test | Score between 0 and 100. The best score 100. | 1-year follow-up | 
| Readmissions due to CV causes | Compare the number of readmissions due to CV causes | 1-year follow-up | 
| Functional change: New York Heart Association. | Evaluate the functional change according to the NYHA scale. Score between 0 and 4. The best score 1. | at 30 days after NOA | 
| Functional change: New York Heart Association. | Evaluate the functional change according to the NYHA scale. Score between 0 and 4. The best score 1. | at 60 days after NOAF | 
| Functional change: New York Heart Association. | Evaluate the functional change according to the NYHA scale. Score between 0 and 4. The best score 1. | at 6 months after NOAF | 
| Functional change: New York Heart Association. | Evaluate the functional change according to the NYHA scale. Score between 0 and 4. The best score 1. | 1-year follow-up | 
| Capacity for the exercise | Evalue the change in capacity for the exercise, evaluated by the 6-minute walk test between groups | at 30 days after NOA | 
| Capacity for the exercise | Evalue the change in capacity for the exercise, evaluated by the 6-minute walk test between groups | at 60 days after NOAF | 
| Capacity for the exercise | Evalue the change in capacity for the exercise, evaluated by the 6-minute walk test between groups | at 6 months after NOAF | 
| Capacity for the exercise | Evalue the change in capacity for the exercise, evaluated by the 6-minute walk test between groups | 1-year follow-up | 
| Incidence of Acute renal failure | Compare the number of events due to acute renal failure between groups | baseline | 
| Incidence of Acute renal failure | Compare the number of events due to acute renal failure between groups | 30 days after NOA |