Clinical trial NCT00523978: A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation
Official title: A Randomized, Controlled Clinical Trial of Catheter Cryoablation in the Treatment of Paroxysmal Atrial Fibrillation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Paroxysmal Atrial Fibrillation
Keywords: Atrial Fibrillation
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
Collaborators: name: Medtronic
First posted: 2007-09-03
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Acute Procedural Success (APS)
timeFrame: 371.4 Minutes (Average)
measure: Freedom From Chronic Treatment Failure (CTF)
timeFrame: 12 month follow up period
measure: Treatment Success
timeFrame: 12 months
measure: Freedom From Major Atrial Fibrillation Events (MAFEs)
timeFrame: 12 Months
measure: Cryoablation Procedure Events (CPEs)
timeFrame: To end of ablation procedure
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Phoenix
country: United States
facility: Banner Good Samaritan Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Cedar Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford Hospital
state: California
city: Colorado Springs
country: United States
facility: Colorado Cardiac Alliance -- Memorial Hospital
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic- Jacksonville
state: Florida
city: Tampa
country: United States
facility: BayHeart Group -- St-Joseph's Hospital
state: Florida
city: Atlanta
country: United States
facility: Emery Crawford Long Hospital
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Hospital
state: Georgia
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania Health
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Heart and Vascular Hospital
state: Texas
city: Falls Church
country: United States
facility: Inova Research Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara CV Research Institute
state: Virginia
city: Richmond
country: United States
facility: Medical College of Virginia
state: Virginia
city: Green Bay
country: United States
facility: Cardiology Associates of Green Bay
state: Wisconsin
city: Milwaukee
country: United States
facility: Arrhythmia Center of Southern WI
state: Wisconsin
city: London
country: Canada
facility: London Medical Health Sciences
state: Ontario
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Ste-Foy
country: Canada
facility: Laval Hospital
state: Quebec
Study officials:
affiliation: Mayo Clinic
name: Douglas L. Packer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, Dubuc M, Reddy V, Nelson L, Holcomb RG, Lehmann JW, Ruskin JN; STOP AF Cryoablation Investigators. Cryoballoon ablation of pulmonary veins for paroxysmal atrial fibrillation: first results of the North American Arctic Front (STOP AF) pivotal trial. J Am Coll Cardiol. 2013 Apr 23;61(16):1713-23. doi: 10.1016/j.jacc.2012.11.064. Epub 2013 Mar 21.