A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation

Paroxysmal Atrial Fibrillation Clinical Trial

— Stop-AF  

Official title:

A Randomized, Controlled Clinical Trial of Catheter Cryoablation in the Treatment of Paroxysmal Atrial Fibrillation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00523978
• Other study ID #: PS-023
• Status: Completed
• Phase: Phase 3
• Start date: October 2006
• Est. completion date: July 2011

Study information

• Verified date: September 2018
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study (STOP AF) is a prospective, randomized, controlled, multicenter, pivotal clinical investigation conducted at 26 investigational sites in the United States and Canada. Subjects with paroxysmal atrial fibrillation (PAF) referred for ablative intervention after efficacy failure of one or more Study Atrial Fibrillation (AF) Drugs (flecainide, propafenone or sotalol) were randomized 2:1 to cryoablation intervention (Experimental Subjects, ES) or to a Study AF Drug (Control Subjects, CS). Subjects were followed for 12 months with scheduled and symptom-driven assessments to detect recurrent atrial fibrillation by means of periodic electrocardiograms, weekly scheduled trans-telephonic monitoring, patient-initiated trans-telephonic monitoring, and 24-hour Holter monitoring at 6 and 12 months. The first 90 days after study therapy was initiated was considered a blanked period for all subjects.

Description:

STOP AF (PS-023) is a randomized, controlled study of subjects 18 to 75 years old who had been referred for ablative intervention after failing one or two (but not all three) anti-arrhythmic drugs used in the treatment of AF (flecainide, propafenone and sotalol). Study subjects were randomized into two arms: the cryoablation (treatment) arm and the membrane-active antiarrhythmic drug (control) arm. A 90- day blanked follow-up period, including reablation and medication adjustments was applied in both arms to optimize therapies. All subjects underwent follow-up assessments at 1, 3, 6, 9 and 12 months, weekly transtelephonic monitoring, 24-hour Holter monitoring and CT/MRI of the pulmonary veins(at 6 and 12 months) during the trial period. Control subjects who were confirmed to be chronic treatment failures were permitted to crossover to cryoablation in this trial.

Acute procedural success was defined for subjects that underwent cryoablation and demonstrated electrical isolation in ≥ 3 Pulmonary Veins (PVs) at the conclusion of the first protocol-defined cryoablation procedure using the Arctic Front® Cardiac CryoAblation Catheter System.

The primary effectiveness endpoint was defined as having acute procedural success and freedom from chronic treatment failure (CTF) for experimental subjects, and freedom from CTF for control subjects. Freedom from (CTF) was defined for both groups as the occurrence of detectable AF during a non-blanked follow-up period, or an AF Intervention, or the use of a non-study AF drug at any time.

The co-primary safety outcome measures were Cryoablation Procedure Events (CPEs) in cryoablated subjects and Major Atrial Fibrillation Events (MAFEs) in both groups. CPEs were device- or procedure-related serious adverse events.

Other safety assessments were made during the course of the STOP AF trial specific to pulmonary vein stenosis (PVS) and phrenic nerve injury.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 245
• Est. completion date: July 2011
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Documented Paroxysmal Atrial Fibrillation (PAF): PAF diagnosis, 2 episodes of PAF within the last 2 months, at least 1 episode of PAF must be documented

• Age 18-75

• Documented Effectiveness Failure of one (1) AF drug

• Willing to be randomized to either group and do full 12 month follow-up

• Able to follow standardized AF drug protocol

Exclusion Criteria:

• Any cardioversion within 3 months or more than 2 within 2 years

• Amiodarone within 6 months

• LA size > 5.0cm

• Previous LA ablation/surgery, structural heart disease, heart failure class III or IV

• Hypertrophic cardiomyopathy, Mitral prosthesis

• Unstable angina, uncontrolled hyperthyroidism

• Stroke or TIA within 6 months, MI within 2 months, cardiac surgery within 3 months

• Thrombocytosis, thrombocytopenia

• Any condition contraindicating chronic anticoagulation

• EF <40%

• Pregnancy

• Life expectancy <1year

Related Conditions & MeSH terms

• Atrial Fibrillation
• Paroxysmal Atrial Fibrillation

Intervention

Device:
• Arctic Front® Cryoablation Catheter
Experimental Subjects received cryoablation intended to isolate the pulmonary veins and ablate arrhythmia foci with the cryoablation catheter system.

Drug:
• Flecainide or Sotalol or Propafenone
Flecainide 200 mg / day Propafenone 450 mg / day Propafenone-SR 650 mg / day Sotalol 240 mg / day

Locations

Country	Name	City	State
Canada	London Medical Health Sciences	London	Ontario
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Laval Hospital	Ste-Foy	Quebec
United States	New Mexico Heart Institute	Albuquerque	New Mexico
United States	Emery Crawford Long Hospital	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	University of Alabama	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Colorado Cardiac Alliance -- Memorial Hospital	Colorado Springs	Colorado
United States	Baylor Heart and Vascular Hospital	Dallas	Texas
United States	Iowa Heart Center	Des Moines	Iowa
United States	Inova Research Center	Falls Church	Virginia
United States	Cardiology Associates of Green Bay	Green Bay	Wisconsin
United States	Mayo Clinic- Jacksonville	Jacksonville	Florida
United States	Cedar Sinai Medical Center	Los Angeles	California
United States	Arrhythmia Center of Southern WI	Milwaukee	Wisconsin
United States	Sentara CV Research Institute	Norfolk	Virginia
United States	University of Pennsylvania Health	Philadelphia	Pennsylvania
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	Medical College of Virginia	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	UC Davis Medical Center	Sacramento	California
United States	Stanford Hospital	Stanford	California
United States	BayHeart Group -- St-Joseph's Hospital	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure	Medtronic

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Procedural Success (APS)	Acute Procedural Success was defined as a demonstration of electrical isolation in = 3 Pulmonary Veins (PVs) at the conclusion of the first protocol-defined cryoablation procedure. APS was decided at the end of the procedure the mean time was calculated for the time frame.	371.4 Minutes (Average)
Primary	Freedom From Chronic Treatment Failure (CTF)	Subjects that did not have or were free of CTF. CTF was defined as the occurence of an Atrial Fibrillation (AF) intervention, use of non-study AF drug therapy, or the occurence of detectable AF which is is defined as an episode of AF, documented in a tracing, and lasting more than 30 seconds, occurring during a Non Blanked Follow-up Period.	12 month follow up period
Primary	Treatment Success	Treatment Success was defined as Acute Procedure Success (APS) and freedom from Chronic Treatment Failure (CTF) for Experimental Subjects, and freedom from CTF for Control Subjects. Under this pre-specified definition of Treatment Success, Experimental Subjects must have had APS and remained free of CTF during the 12-month follow-up duration, while Control Subjects must have remained free of CTF during the 12-month follow-up duration.	12 months
Primary	Freedom From Major Atrial Fibrillation Events (MAFEs)	Subjects that did not have or were free of MAFEs. MAFEs were serious adverse events categorized as cardiovascular death, myocardial infarction, stroke, or hospitalization for AF recurrence/ablation, flutter ablation, embolic events, heart failure, hemorrhage or anti-arrhythmic drug treatment.	12 Months
Primary	Cryoablation Procedure Events (CPEs)	Subjects that had CPEs. CPEs were device- or procedure-related serious adverse events (SAE) categorized as access site complications, cardiac damage, pulmonary vein (PV) stenosis, embolic complications, arrhythmias, unresolved phrenic nerve palsy and death.	To end of ablation procedure