Boston Scientific's Cryoballoon in the Treatment of Symptomatic Drug Refractory Paroxysmal Atrial Fibrillation (FROZEN-AF)

Safety and Effectiveness IDE Trial for Boston Scientific's Cryoballoon in the Treatment of Symptomatic Drug Refractory Paroxysmal Atrial Fibrillation

To establish the safety and effectiveness of the Boston Scientific Cardiac Cryoablation System for treatment of symptomatic, drug refractory, recurrent, paroxysmal atrial fibrillation (AF).

Study Overview

• Status: Completed
• Conditions: Paroxysmal Atrial Fibrillation
• Intervention / Treatment: Device: Boston Scientific Cardiac Cryoablation System

Detailed Description

Multi-center, open label, prospective, single arm study to document the safety and performance of Boston Scientific's Cryoablation System. The Cryoablation System is intended for cryoablation and electrical mapping of the pulmonary veins for pulmonary vein isolation (PVI) in the ablation treatment of patients with paroxysmal atrial fibrillation (PAF). All subjects fitting the enrollment criteria, signing the consent and undergoing the index procedure with the study devices will be followed up for twelve (12) months after the index procedure.

• Study Type: Interventional
• Enrollment (Actual): 458
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • UZ Brussels
• Canada
  • Montreal, Canada
    • Institut de Cardiologie de Montreal
  • Quebec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
  • Vancouver, Canada
    • Vancouver General Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
• France
  • Grenoble, France, 38043
    • CHU Grenoble - Hopital Michallon
• Germany
  • Bad Oeynhausen, Germany
    • Herz-und Diabeteszentrum Nordrhein-Westfalen
  • Lübeck, Germany, D-23538
    • Universitaetsklinikum Schleswig-Holstein
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Cotignola, Italy
    • Maria Cecilia Hospital SPA
• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC- University Medical Center Rotterdam
• Taiwan
  • Beitou District
    • Taipei, Beitou District, Taiwan, 11217
      • Taipei Veterans General Hospital
  • Zhongzheng Dist
    • Taipei City, Zhongzheng Dist, Taiwan, 10002
      • National Taiwan University Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
    • Tucson, Arizona, United States, 85712
      • Pima Heart and Vascular
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Arrhythmia Research Group
  • California
    • Los Angeles, California, United States, 90048
      • Cedars - Sinai Medical Center
    • Sacramento, California, United States, 95819
      • Mercy General Hospital
    • Torrance, California, United States, 90505
      • Torrance Memorial Medical Center
  • Florida
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
    • Tampa, Florida, United States, 33613
      • AdventHealth Tampa
    • Tampa, Florida, United States, 33614
      • St. Joseph's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Emory University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Southcoast Physicians Group
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Hospital of Kansas City
  • New Jersey
    • Ridgewood, New Jersey, United States, 07450-2736
      • Valley Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
    • Staten Island, New York, United States, 10305
      • Northwell Health
    • Syracuse, New York, United States, 13203
      • St. Joseph's Hospital Health Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • York, Pennsylvania, United States, 17403
      • York Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation, Inc.
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor Heart & Vascular Hospital
    • Tyler, Texas, United States, 75702
      • Christus Trinity Mother Frances Health System
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Health System
    • Richmond, Virginia, United States, 23225
      • Chippenham & Johnston-Willis Hospital
  • Washington
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical
  • West Virginia
    • Huntington, West Virginia, United States, 25702
      • St. Mary's Medical Center
  • Wisconsin
    • Grafton, Wisconsin, United States, 53024
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of recurrent symptomatic paroxysmal atrial fibrillation (PAF), defined as atrial fibrillation that terminates spontaneously or with intervention (either procedure or drug therapy) within seven days of onset. Minimum documentation includes the following:

  • a physician's note indicating recurrent self-terminating atrial fibrillation (AF) which includes at least two symptomatic AF episodes within six months prior to enrollment, and one electrocardiographically documented AF episode within 12 months prior to enrollment.
• No amiodarone use within 90 days prior to enrollment;
• Subjects who are indicated for an ablation procedure for paroxysmal atrial fibrillation (PAF) according to 2017 HRS expert consensus statement on catheter and surgical ablation of atrial fibrillation;
• Subjects refractory or intolerant to at least one class I or III antiarrhythmic medication;
• Subjects who are willing and capable of providing informed consent;
• Subjects who are willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center;
• Subjects whose age is 18 years or above, or who are of legal age to give informed consent specific to state and national law.

Exclusion Criteria:

• Any known contraindication to an AF ablation or anticoagulation;
• Continuous AF lasting longer than seven (7) days from onset;
• History of previous left atrial ablation or surgical treatment for AF/ AFL/ AT;
• Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or any other reversible or non-cardiac cause;

• Structural heart disease or implanted devices as described below:

  1. Left ventricular ejection fraction (LVEF) < 40% based on the most recent transthoracic echocardiogram (TTE) (≤180 days prior to enrollment);
  2. Left atrial diameter > 55 mm OR left atrial volume > 50 ml/m2 ml indexed based on the most recent TTE (≤ 180 days prior to enrollment);
  3. An implanted pacemaker, ICD, CRT device or an arrhythmia loop recorder;
  4. Previous cardiac surgery: i.e. ventriculotomy or atriotomy (excluding atriotomy for CABG);
  5. Previous cardiac valvular surgical or percutaneous procedure, or prosthetic valve, including mitral valve clips;
  6. Interatrial baffle, closure device, patch, or patent foramen ovale (PFO) occlude;
  7. Presence of a left atrial appendage occlusion device;
  8. Presence of any pulmonary vein stents;
  9. Coronary artery bypass graft (CABG), PTCA/ PCI/ coronary stent procedures within 90 days prior to enrollment;
  10. Unstable angina or ongoing myocardial ischemia;
  11. myocardial infarction within 90 days prior to enrollment;
  12. Moderate or severe mitral insufficiency assessed on the most recent TTE (≤180 days prior to enrollment, e.g. pulmonary artery pressure >30 mmHg);
  13. Evidence of left atrial thrombus;
• Any previous history of cryoglobulinemia;
• Stage 3B or higher renal disease (estimated glomerular filtration rate, eGFR <45 mL/min);
• History of blood clotting or bleeding disease;
• Any prior history of documented cerebral infarct, TIA or systemic embolism [excluding a post-operative deep vein thrombosis (DVT)] ≤180 days prior to enrollment;
• Active systemic infection;
• Pregnant, lactating (current or anticipated during study follow up), or women of childbearing potential who are, or plan to become, pregnant during the time of the study (method of assessment upon physician's discretion);
• Subjects who are currently enrolled in another investigational study or registry that would directly interfere with the current study, except when the subject is participating in a mandatory governmental registry, or a purely observational registry with no associated treatments; each instance must be brought to the attention of the sponsor to determine eligibility;
• Subjects who in the judgment of the investigator have a life expectancy of less than two years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Cryoablation; Subjects undergoing cardiac ablation procedure with the Boston Scientific Cardiac Cryoablation System

Device: Boston Scientific Cardiac Cryoablation System; The Boston Scientific Cardiac Cryoablation System is intended for ablation and electrical mapping of the pulmonary veins for pulmonary vein isolation (PVI) in the ablation treatment of patients with paroxysmal atrial fibrillation (PAF).The main devices and components of the system consists of the following: POLARx™ or POLARx™ FIT Cryoablation Catheter; POLARMAP™ Catheter; POLARSHEATH™; SMARTFREEZE™ Console; Diaphragm Movement Sensor (DMS); Related Accessories

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Freedom From Primary Safety Events at 12 Months Post-procedure (Acute and Chronic Events) Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter Models	This measure reports the observed safety event-free rate at 12 Months follow up for all Non Roll-In treatment and intent subjects. The safety events are a composite of procedure-related and device-related adverse events. 7 days (Death, Myocardial infarction, Transient ischemic attack, Stroke/ Cerebrovascular accident, Vascular access complications, Mitral or tricuspid valvular damage, Thromboembolism/ Air embolism leading to a life-threatening event such as a ventricular arrhythmia, stroke, pulmonary embolism, or myocardial infarction and, thromboembolic events that result in permanent injury, require intervention for treatment or prolongs or require hospitalization for more than 48 hours, Gastroparesis/injury to vagus nerve, Pneumothorax, Pulmonary edema/heart failure AV block); 30 days (Cardiac tamponade/perforation); 12 months: (Atrial esophageal fistula, Severe Pulmonary vein stenosis, Persistent phrenic nerve palsy .	12 Months
Percentage of Participants With Freedom From Treatment Failure at 12 Months Post-procedure Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter Models	Freedom from the composite of: Failure to achieve acute procedural success in the index procedure or repeat procedure during the blanking period; Use of amiodarone post index procedure; Surgical treatment for AF/AFL/AT post index procedure; Use of non-study ablation catheter for AF targets in the index procedure or repeat procedure during the blanking period; More than one repeat procedure with the POLARx catheter during the blanking period (90 days post index procedure); Documented AF, or new onset of AF or AT event 91-365 days post index procedure; Any of the following for AF, or new onset of AF or AT 91-365 days post index procedure: Repeat procedure - Electrical and/or pharmacological cardioversion for AF/AFL/AT - Prescribed AAD consisting of any Class I/III, including Amiodarone, and any Class II/IV medications taken for control of AF, AT, AFL recurrence	12 Months
Percentage of Participants With Freedom From Primary Safety Events at 3 Months Post Procedure Using the Boston Scientific Cardiac Cryoablation System With POLARx FIT Cryoablation Balloon Catheter Models	Composite of procedure-related and device-related adverse events. 7 days post index procedure or hospital discharge, whichever is later, unless denoted as events counting through 3 months post index procedure (Death, Myocardial infarction, Major Vagal Nerve Injury/Gastroparesis, Transient ischemic attack, Stroke/Cerebrovascular accident, Thromboembolism, Cardiac tamponade/perforation, Pneumothorax, Major vascular access complications, Pulmonary edema/heart failure, AV block, Atrial esophageal fistula, severe pulmonary vein stenosis (≥70% reduction in the diameter of the PV or PV branch from baseline), Persistent phrenic nerve palsy)	3 months
Percentage of Participants With Acute Procedural Success Defined as the Achievement of Electrical Isolation of All PVs by Using the Boston Scientific Cardiac Cryoablation System With POLARx Fit Cryoablation Balloon Catheter Models	The primary effectiveness endpoint is the rate of acute procedural success where acute procedural success is defined as the achievement of electrical isolation of all PVs by using the Cardiac Cryoablation System with the POLARx FIT cryoablation balloon catheter models (with treatment applied at 28 mm or 31 mm balloon size per physician discretion). Electrical isolation of a PV is demonstrated by entrance and exit block.	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Acute Procedural Success Defined as the Achievement of Electrical Isolation of All PVs by Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter	The achievement of electrical isolation of all PVs by using the POLARx Cardiac Cryoablation System. Electrical isolation of a PV is demonstrated by entrance and exit block.	1 day
Number of Participants With Freedom From Reportable Adverse Events at 12 Months Post Procedure Using the Boston Scientific Cardiac Cryoablation System With POLARx Cryoablation Balloon Catheter Models	All Serious Adverse Events; All Study Procedure-Related Adverse Events; All Study Device-Related Adverse Events; All Study Device Deficiencies; Unanticipated Adverse Device Effects/Unanticipated Serious Adverse Device Effects previously not defined in Investigator's Brochure or DFU	12 months
Percentage of Participants With Freedom From Safety Events at 12 Months Post Procedure Using the Boston Scientific Cardiac Cryoablation System Using the Boston Scientific Cardiac Cryoablation System With POLARx FIT Cryoablation Balloon Catheter Models	The following events will be counted through 7 days post index procedure or hospital discharge, whichever is later: Death, Myocardial infarction, Major Vagal Nerve Injury/Gastroparesis, Transient ischemic attack, Stroke/Cerebrovascular accident, Thromboembolism, Pneumothorax, Major vascular access complications, Pulmonary edema/heart failure, AV block. The following event will be counted through 30 days post index procedure: Cardiac tamponade/perforation. The following events will be counted through 12 months post index procedure: Atrial esophageal fistula, Severe pulmonary vein stenosis (≥70% reduction in the diameter of the PV or PV branch from baseline), Persistent phrenic nerve palsy.	12 Months
Percentage of Participants With Freedom From Treatment Failure at 12 Months Post-procedure Using the Boston Scientific Cardiac Cryoablation System With POLARx FIT Cryoablation Balloon Catheter Models	Freedom from the composite of: Failure to achieve acute procedural success in the index procedure or repeat procedure during the blanking period; Use of amiodarone post index procedure; Surgical treatment for AF/AFL/AT post index procedure; Use of non-study ablation catheter for AF targets in the index procedure or repeat procedure during the blanking period; More than one repeat procedure with the Cryoablation System during the blanking period (90 days post index procedure); Documented AF, or new onset of AF or AT event 91-365 days post index procedure; Any of the following for AF, or new onset of AF or AT 91-365 days post index procedure: Repeat procedure - Electrical and/or pharmacological cardioversion for AF/AFL/AT - Prescribed AAD consisting of any Class I/III, including Amiodarone, and any Class II/IV medications taken for control of AF, AT, AFL recurrence	12 Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Freedom From Recurrence	The following analysis looks at the recurrence free rate of individual atrial arrhythmia types as documented on a rhythm monitoring device post- blanking period.	12 Months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Study Chair: Kenneth Ellenbogen, MD, VCU Pauley Heart Center, Richmond, Virginia, USA; Principal Investigator: Arash Aryana, MD, PhD, Mercy General Hospital,Sacramento, CA , USA; Principal Investigator: Nassir Marrouche, MD, University of Utah School of Medicine. Slat Lake City, UT, USA; Principal Investigator: Ante Anić, MD, University Hospital, Split, Croatia; Principal Investigator: Suneet Mittal, MD,FACC,FHRS, Snyder AF Center, New York, NY, USA; Principal Investigator: Niraj Varma, MD,PhD,FRCP, Cleveland Clinic, Cleveland OH, USA; Principal Investigator: Wilber W Su, MD,FACC,FHRS, Banner- University Medical Group- Heart Center, Phoenix, AZ, USA

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): November 10, 2022
• Study Completion (Actual): August 17, 2023

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 5, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: cryoablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: PY004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No requests for study data have been made at this time, however Boston's Scientific's policy on data sharing can be found at http://www.bostonscientific.com/en-US/data-sharing-requests.html

Drug and device information, study documents

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