A Time-to-effect Based Dosing Strategy in Cryoballoon Ablation of Patients With Paroxysmal Atrial Fibrillation

Study Overview
=================
Brief Summary
-----------------
This study aims to validate a new dosage of cryotherapy based on time to effect in pulmonary vein ablation procedures in patients with paroxysmal atrial fibrillation.

Official Title
-----------------
A Time-to-effect Based Dosing Strategy in Cryoballoon Ablation of Patients With Paroxysmal Atrial Fibrillation. Results of the the plusONE Randomized Multicenter Trial

Conditions
-----------------
Atrial Fibrillation

Intervention / Treatment
-----------------
* Other: Conventional cryotherapy dosage
* Other: Experimental cryotherapy dosage
* Device: Arctic Front Advance ST Cryoenergy Balloon Catheter
* Drug: Adenosine triphosphate
* Device: nECG platform Nuubo®


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with at least 2 documented episodes of paroxysmal Atrial Fibrillation (AF) which are not responders to at least one antiarrythmic drug Exclusion Criteria: Previous left atrial ablation procedure or surgery left atrium diameter > 50mm presence of intracardiac thrombus Left ventricular ejection fraction < 40% Heart failure class III-IV Severe valvulopathies Acute coronary syndrome or cardiac surgery within the previous 3 months of enrollment Transient ischemic attack/stroke within the previous 6 months of enrollment life expectancy less than 1 year Any contraindication to the procedure according to the current clinical practice

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control Arm<br>Conventional protocol for cryoablation: At least 2 applications of 180s each | Other: Conventional cryotherapy dosage<br>* Cryotherapy dosage: 180 seconds applications until block of the pulmonary vein plus 1 bonus freezing of 180 seconds<br>Device: Arctic Front Advance ST Cryoenergy Balloon Catheter<br>* Electrical isolation of pulmonary veins with Arctic Front Advance cryoballoon<br>Drug: Adenosine triphosphate<br>* 12 mg of adenosine triphosphate are administrated intravenously to test dormant conduction in pulmonary veins apparently disconnected<br>Device: nECG platform Nuubo®<br>* 30 days electrocardiographic monitoring system to detect atrial fibrillation episodes after ablation<br>|
| Experimental: Study Arm<br>Experimental protocol for cryoablation: Time to effect + 1 minute and a bonus application of 120s | Other: Experimental cryotherapy dosage<br>* cryotherapy dosage: applications time to block of the vein plus 60 seconds long until block of the vein plus 1 bonus freezing of 120 seconds<br>Device: Arctic Front Advance ST Cryoenergy Balloon Catheter<br>* Electrical isolation of pulmonary veins with Arctic Front Advance cryoballoon<br>Drug: Adenosine triphosphate<br>* 12 mg of adenosine triphosphate are administrated intravenously to test dormant conduction in pulmonary veins apparently disconnected<br>Device: nECG platform Nuubo®<br>* 30 days electrocardiographic monitoring system to detect atrial fibrillation episodes after ablation<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Atrial fibrillation-free survival, without antiarrhythmic drug therapy |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean number of cryotherapy applications per patient to complete isolation |  | Intraprocedural | 
| Total cryotherapy time | Total cryotherapy time of applications needed per patient | Intraprocedure | 
| Time required to complete isolation of all the pulmonary veins (LA time) | Time from the end of transeptal approach until the withdrawal of the cryoballoon | Intraprocedure | 
| Total procedure time | Time from the local anesthesia is administrated until the whole procedure is finished | Intraprocedure | 
| Acute reconnection of pulmonary veins | Number of veins reconnected after a 30 minutes waiting period since the end of procedure and with adenosine test | Intraprocedure | 
| Adverse events | Number of participants with procedural-related adverse events as assessed by by CTCAE v4.0 | Intraprocedure | 
| Total number of atrial fibrillation episodes monitored by Nuubo system |  | 12 Months | 
| Total time in atrial fibrillation monitored by Nuubo system | Total time in atrial fibrillation monitored by Nuubo system in hours | 12 months | 
| Atrial fibrillation burden detected by Nuubo system | total time in atrial fibrillation related to the hole time of monitoring (percentage) | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cryotherapy