STOP AF First: Cryoballoon Catheter Ablation in an Antiarrhythmic Drug Naive Paroxysmal Atrial Fibrillation (STOP AF First)

To provide data demonstrating the safety and effectiveness of the Arctic Front Advance™ Cardiac CryoAblation Catheter for the treatment of recurrent symptomatic paroxysmal atrial fibrillation, without the requirement that the subjects be drug refractory.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation; Atrial Fibrillation New Onset
• Intervention / Treatment: Drug: Antiarrhythmic drug; Device: Cryoablation

Detailed Description

Subjects with paroxysmal atrial fibrillation with no history of treatment with anti-arrhythmic drugs are randomized 1:1 to either an anti-arrhythmic drug or pulmonary vein isolation using the cryoballoon catheter.

• Study Type: Interventional
• Enrollment (Actual): 225
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Grandview Medical Center
  • Alaska
    • Anchorage, Alaska, United States, 50266-8209
      • Alaska Heart Institute
  • California
    • Newport Beach, California, United States, 92663
      • Hoag Hospital Newport Beach
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-3017
      • Medstar Washington Hospital Center
  • Florida
    • Tallahassee, Florida, United States, 32308-4646
      • Tallahassee Research Institute Inc
    • Tampa, Florida, United States, 33607
      • BayCare Medical Group Cardiology
  • Georgia
    • Marietta, Georgia, United States, 30060
      • WellStar Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Krannert Institute of Cardiology
  • Iowa
    • West Des Moines, Iowa, United States, 50266-8209
      • Iowa Heart Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 50266-8209
      • Our Lady of the Lake Office of Research
  • Massachusetts
    • New Bedford, Massachusetts, United States, 02740
      • Southcoast Health System
  • Michigan
    • Ann Arbor, Michigan, United States, 50266-8209
      • University of Michigan Health System - University Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Hospitals
  • Minnesota
    • Saint Paul, Minnesota, United States, 55102-1062
      • HealthEast Saint Josephs Hospital
  • Nebraska
    • Lincoln, Nebraska, United States, 07450-2726
      • Bryan Heart
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Ridgewood, New Jersey, United States, 07450-2726
      • The Valley Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195-0001
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112-4418
      • INTEGRIS Baptist Medical Center, Inc.
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Lehigh Valley Health
    • Danville, Pennsylvania, United States, 17821
      • Geisinger Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 50266-8209
      • Aurora Cardiovascular Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A diagnosis of symptomatic paroxysmal AF with the following documentation: (1) physician's note indicating recurrent self- terminating AF or paroxysmal AF; and (2) any ECG documented AF within 6 months prior to enrollment.
• Age 18-80

Exclusion Criteria:

• History of AF treatment with class I or III antiarrhythmic drug, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode are allowed.
• Prior persistent AF (cardioversion after 48 hours or continuous AF that is sustained >7 days)
• Left atrial diameter greater than 5.0 cm
• Prior left atrial ablation or left atrial surgical procedure
• Presence or likely implant of a permanent pacemaker, biventricular pacemaker, loop recorder, or any type of implantable cardiac defibrillator (with or without biventricular pacing function)
• Body mass index (BMI) >35 kg/m2
• Presence of any pulmonary vein stents
• Known presence of any pre-existing pulmonary vein stenosis
• Pre-existing hemidiaphragmatic paralysis
• Presence of any cardiac valve prosthesis
• Moderate or severe mitral valve regurgitation or stenosis
• Any cardiac surgery, myocardial infarction, percutaneous coronary intervention/ percutaneous transluminal coronary angioplasty or coronary artery stenting which occurred during the 90 day interval preceding the date the subject signed the Informed Consent Form
• Unstable angina
• New York Heart Association (NYHA) class III or IV congestive heart failure and/or known left ventricular ejection fraction (LVEF) less than 45%
• Diagnosis of primary pulmonary hypertension
• Rheumatic heart disease
• Thrombocytosis, thrombocytopenia
• Contraindication to anticoagulation therapy
• Active systemic infection
• Hypertrophic cardiomyopathy
• Cryoglobulinemia
• Known reversible causes of AF, including but not limited to uncontrolled hyperthyroidism, obstructive sleep apnea, and acute alcohol toxicity.
• Any cerebral ischemic event (strokes or transient ischemic attacks) which occurred during the 180 day interval preceding the date the subject signed the Informed Consent Form, or any known unresolved complications from previous stroke/transient ischemic attack
• Existing thrombus
• Pregnancy
• Patient with life expectancy that makes it unlikely 12 months of follow-up will be completed.
• Current or anticipated participation in any other clinical trial of a drug, device or biologic during the duration of this study not pre-approved by Medtronic
• Patients with contraindications to a Holter monitor
• Unwilling or unable to comply fully with study procedures and follow-up

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cryoablation	Device: Cryoablation; Pulmonary vein isolation via ablation with cryoballoon catheter; Other Names: ArcticFront Advance Cardiac CryoAblation Catheter
Active Comparator: Anti-arrhythmic drug	Drug: Antiarrhythmic drug; Antiarrhythmic drug initiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Success at 12 Months After Antiarrhythmic Drug (AAD) Initiation or Ablation Utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter.	Treatment success after AAD initiation (control arm) or pulmonary vein isolation ablation procedure utilizing the Arctic Front Advance™ Cardiac CryoAblation Catheter (treatment arm). Treatment success is the opposite of treatment failure. Treatment failure was defined as any of the following: Acute procedural failure (treatment arm only).; Documented AF/AT/AFL on ambulatory monitoring/12-lead ECG after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm). Minimum of 30 seconds on ambulatory monitoring or 10 seconds on 12-lead ECG.; Any subsequent AF surgery or ablation in the left atrium.; Any subsequent cardioversion after the 90-day post-ablation blanking period (treatment)/AAD optimization period (control arm).; Class I or III antiarrhythmic drug (or sotalol) use after the 90-day blanking period (treatment arm only).	Randomization to 12 months
Primary Safety Endpoint - Rate of Composite List of Serious Adverse Events.	Measured by rate of composite list of serious adverse events in cryoablation-treated as randomized arm. Includes: TIA within 7 days; Cerebrovascular accident within 7 days; Major bleed that requires transfusion or results in a 20% or greater fall in hematocrit (HCT) within 7 days; Development of a significant pericardial effusion within 30 days. (One that results in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in a 1-cm or more pericardial effusion as documented by echocardiography).; Symptomatic PV stenosis within 12 months; accompanied by one of the following: 50%-75% reduction in diameter of the pulmonary vein, with symptoms not explained by other conditions; OR >75% reduction in diameter of the pulmonary vein; MI within 7 days; PNI unresolved at 12 months; AE fistula within 12 months; Major vascular complication that requires intervention, prolongs hospital stay, or requires hospital admission (within 7 days).	Randomization to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life Scores at Baseline Compared to 12 Months	There are two hypotheses tested in the objective, with separate hypothesis tests for (1) the difference in composite scores from the AFEQT questionnaire taken at baseline and 12 month visits, and (2) for the difference in composite scores for the EQ-5D questionnaire taken at baseline and 12-month visits. Composite AFEQT score is on a scale of zero to one hundred. Higher scores are better. Composite EQ-5D score is on a scale of zero to one. Higher scores are better.	Baseline and 12 Months
Healthcare Utilization	Compare health care utilization between the treatment and control arms. There are two hypotheses tested in the objective, with separate hypothesis tests for: (1) the rate of total health care utilization events (cardiovascular-related hospitalizations, emergency room visits, or unscheduled office visits) over 12 months shown as freedom from cardiovascular health care utilization by treatment arm, and (2) freedom from cardioversions (electrical or pharmacological) over 12 months by treatment arm.	Initial treatment through 12 months.

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: Oussama Wazni, MD, The Cleveland Clinic; Principal Investigator: Gopi Dandamudi, MD, Franciscan Heart & Vascular Associates at St. Joseph; Principal Investigator: Steve Nissen, MD, The Cleveland Clinic

Publications and helpful links

General Publications

• Wazni OM, Dandamudi G, Sood N, Hoyt R, Tyler J, Durrani S, Niebauer M, Makati K, Halperin B, Gauri A, Morales G, Shao M, Cerkvenik J, Kaplon RE, Nissen SE; STOP AF First Trial Investigators. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):316-324. doi: 10.1056/NEJMoa2029554. Epub 2020 Nov 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2017
• Primary Completion (Actual): June 25, 2020
• Study Completion (Actual): June 25, 2020

Study Registration Dates

• First Submitted: April 4, 2017
• First Submitted That Met QC Criteria: April 17, 2017
• First Posted (Actual): April 18, 2017

Study Record Updates

• Last Update Posted (Actual): August 11, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anti-Arrhythmia Agents
• Other Study ID Numbers: MDT16012AFS001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes