Persistent Atrial Fibrillation Clinical Trial
— AVANT GUARDOfficial title:
A Prospective Randomized Multicenter Global Study Comparing Pulsed Field Ablation (PFA) Versus Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation
The purpose of this study is to establish the safety and effectiveness of pulsed field ablation as a first-line ablation treatment for subjects with persistent atrial fibrillation as compared to subjects who received an initial treatment with anti-arrhythmic drugs.
Status | Recruiting |
Enrollment | 387 |
Est. completion date | December 30, 2027 |
Est. primary completion date | December 25, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - 1. Age = 18 years of age, or older if specified by local law - 2. Have symptomatic persistent AF, confirmed by both: 1. Documentation, within 180 days of randomization, or treatment assignment for roll-in subjects, of either: i. A 24-hour continuous ECG recording (from any regulatory cleared rhythm monitoring device) confirming continuous AF, OR ii. Two ECGs (from any regulatory cleared rhythm monitoring device) showing continuous AF taken at least 7 days apart 2. Documentation, such as physician note, of persistent continuous AF for > 7 days and = 365 days - 3. Willing and capable of providing informed consent - 4. Willing and capable of participating in all testing associated with this clinical investigation at an approved clinical investigational center - 5. Willing to receive LUX-Dx™ insertable cardiac monitor (ICM) during the study or already has a LUX-Dx™ ICM that was inserted = 6 months of consent Exclusion Criteria: - 1. Over the 6 months preceding enrollment, more than 7-day history of therapeutic AAD use (Class I or III), or = 24 hours amiodarone, except for pill-in-the-pocket AAD use, which is permitted. Or, treated with AAD > 6 months preceding enrollment and experienced AAD failure (adverse drug effects or frequent AF episodes) - 2. Any of the following atrial conditions: 1. Left atrial (LA) anteroposterior diameter = 5.5 cm, or, if LA diameter not available, non-indexed volume >100 ml, as documented by physician note or imaging (Note: if both values are available, only the LA diameter will be used to confirm eligibility criteria) 2. Any prior atrial endocardial, epicardial or surgical ablation procedure for arrhythmia, other than right sided cavotricuspid isthmus ablation or for right sided supraventricular tachycardia 3. Current atrial myxoma 4. Any PV abnormality, stenosis, or stenting (common and middle PVs are admissible) 5. Current left atrial thrombus - 3. Any of the following cardiovascular conditions: 1. History of sustained ventricular tachycardia or any ventricular fibrillation 2. AF that is secondary to electrolyte imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes 3. Current or anticipated pacemaker, implantable cardioverter defibrillator or cardiac resynchronization therapy devices, interatrial baffle, atrial septal patch, atrial septal defect closure device, or patent foramen ovale occluder 4. Valvular disease that is any of the following: i. Symptomatic, ii. Causing or exacerbating congestive heart failure, iii. Associated with abnormal left ventricular (LV) function or hemodynamic measurements 5. Hypertrophic cardiomyopathy 6. Cardiac amyloidosis 7. Any prosthetic heart valve, ring or repair including balloon aortic valvuloplasty 8. Any inferior vena cava (IVC) filter, known inability to obtain vascular access or other contraindication to femoral access 9. Rheumatic heart disease 10. Congenital heart disease with any clinically significant residual anatomic or conduction abnormality 11. Awaiting cardiac transplantation or other cardiac surgery within the next 12 months - 4. Any of the following conditions identified during screening assessments 1. Heart failure associated with New York Heart Association (NYHA) Class IV 2. Left Ventricle Ejection Fraction (LVEF) < 40% 3. Uncontrolled hypertension (Systolic Blood Pressure > 160 mmHg or Diastolic Blood Pressure > 95 mmHg on two (2) BP measurements during screening - 5. Any of the following events 90 days prior to randomization (or Index procedure for roll-in subjects): 1. Myocardial infarction (MI), unstable angina or coronary intervention 2. Cardiac surgery 3. Heart failure hospitalization 4. Pericarditis or symptomatic pericardial effusion 5. Gastrointestinal bleeding 6. Stroke, TIA, or intracranial bleeding 7. Non-neurologic thromboembolic event 8. Carotid stenting or endarterectomy - 6. Thrombocytosis, thrombocytopenia, disorder of blood clotting or bleeding diathesis - 7. Contraindication to, or unwillingness to use, systemic anticoagulation, AADs (Class I and III, excluding amiodarone which is not allowed during the study), and PFA treatment - 8. Unwillingness to receive, or unable to tolerate, a subcutaneous, chronically inserted LUX-Dx™ ICM device - 9. Women of childbearing potential who are pregnant, lactating, not using a reliable form of contraception, or who are planning to become pregnant during the anticipated study period - 10. Body Mass Index (BMI) > 45 - 11. Solid organ or hematologic transplant, or currently being evaluated for a transplant - 12. Any prior history or current evidence of hemi-diaphragmatic paralysis or paresis - 13. Severe lung disease, or any lung disease involving abnormal blood gases or requiring supplemental oxygen - 14. Severe pulmonary hypertension during screening assessment - 15. Renal insufficiency if an estimated glomerular filtration rate (eGFR) is < 30 mL / min / 1.73 m2, or with any history of renal dialysis or renal transplant - 16. Active malignancy at enrollment (other than cutaneous basal cell or squamous cell carcinoma) - 17. Clinically significant gastrointestinal problems involving the esophagus or stomach including severe or erosive esophagitis, uncontrolled gastric reflux, gastroparesis, esophageal candidiasis or active gastroduodenal ulceration - 18. Known active systemic infection - 19. Known positive test for Coronavirus Disease 2019 (COVID-19) and disease not clinically resolved - 20. Uncontrolled diabetes mellitus or a recorded HgbA1c > 8.0% in the 90 days prior to randomization (or Index procedure for roll-in subjects) - 21. Untreated diagnosed obstructive sleep apnea with apnea hypopnea index classification of severe (>30 pauses per hour) - 22. Predicted life expectancy less than one (1) year - 23. Currently enrolled in another investigational study or registry that would directly interfere with this 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 - 24. Health conditions that, in the investigator's medical opinion, would prevent participation in the study, interfere with assessment or therapy, significantly raise the risk of study participation, or modify outcome data or its interpretation - 25. Has operational LUX-Dx ICM that was inserted more than 6 months prior to enrollment - 26. Has operational ICM other than a LUX-Dx ICM and does not express a willingness to receive a LUX-Dx ICM for the study - 27. Individuals who may require an ablation, besides the PV and PW, in the left atrium including, but not limited to, those with Left-Sided Atrioventricular Reentrant Tachycardia (AVRT), Left-Sided Atrial Tachycardia (AT), or Atypical Left-Sided Atrial Flutter. |
Country | Name | City | State |
---|---|---|---|
Australia | The Prince Charles Hospital | Chermside | Queensland |
Australia | Monash Medical Centre | Clayton | Victoria |
Belgium | St. Jan | Brugge | |
Canada | Hamilton General Hospital | Hamilton | Ontario |
Canada | Institut universitaire de Cardiologie et de Pneumologie de Quebec | Québec | Quebec |
Canada | Vancouver General Hospital | Vancouver | |
Croatia | Klinicki Bolnicki Centar Split | Split | |
Germany | Cardioangiologisches Centrum Bethanien | Frankfurt | |
Italy | AOU delle Marche - PO GM Lancisi | Ancona | AN |
Italy | Maria Cecilia Hospital SPA | Cotignola | RA |
Italy | Centro Cardiologico Monzino | Milano | MI |
Singapore | National Heart Centre Singapore | Singapore | |
Spain | Hospital Universitario La Fe | Valencia | |
United States | University of Michigan Hospitals | Ann Arbor | Michigan |
United States | Memorial Mission Hospital-Hospital | Asheville | North Carolina |
United States | Emory University Hospital | Atlanta | Georgia |
United States | Texas Cardiac Arrhythmia Research | Austin | Texas |
United States | Johns Hopkins Hospital | Baltimore | Maryland |
United States | Northwell Health | Bay Shore | New York |
United States | University of Alabama at Birmingham | Birmingham | Alabama |
United States | Brigham and Women's Hospital | Boston | Massachusetts |
United States | Massachusetts General Hospital | Boston | Massachusetts |
United States | Kaleida Health | Buffalo | New York |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Bethesda North Hospital | Cincinnati | Ohio |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | OhioHealth Research and Innovation Institute - Riverside Methodist Hospital | Columbus | Ohio |
United States | Duke University Medical Center | Durham | North Carolina |
United States | University of Texas Medical Branch | Galveston | Texas |
United States | Corewell Health | Grand Rapids | Michigan |
United States | Orion Medical | Houston | Texas |
United States | Community Heart and Vascular Hospital | Indianapolis | Indiana |
United States | Arrhythmia Research Group | Jonesboro | Arkansas |
United States | Catholic Medical Center | Manchester | New Hampshire |
United States | HCA Florida Mercy Hospital | Miami | Florida |
United States | Aurora St. Luke's Medical Center | Milwaukee | Wisconsin |
United States | Intermountain Medical Center | Murray | Utah |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Weill Cornell Medical University | New York | New York |
United States | Stanford University Medical Center | Palo Alto | California |
United States | Banner University Medical Center Phoenix | Phoenix | Arizona |
United States | Phoenix Cardiovascular Research Group | Phoenix | Arizona |
United States | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania |
United States | Southcoast Physicians Group | Providence | Rhode Island |
United States | Chippenham & Johnston-Willis Hospital (CJW) | Richmond | Virginia |
United States | Mayo Clinic Foundation-Hospital | Rochester | Minnesota |
United States | Sarasota Memorial Hospital | Sarasota | Florida |
United States | Memorial Health University Medical Center | Savannah | Georgia |
United States | St. John's Hospital | Springfield | Illinois |
United States | Good Samaritan - Suffern | Suffern | New York |
United States | Tallahassee Memorial Hospital | Tallahassee | Florida |
United States | St. Joseph's Hospital | Tampa | Florida |
United States | Oklahoma Heart Institute | Tulsa | Oklahoma |
United States | Christus Trinity Mother Frances Health System | Tyler | Texas |
United States | Cardiology Associates Medical Group, Inc | Ventura | California |
United States | University of Iowa Hospitals and Clinics | West Burlington | Iowa |
United States | Mercy Hospital Medical Center-Hospital | West Des Moines | Iowa |
United States | Wake Forest University School of Medicine | Winston-Salem | North Carolina |
United States | York Hospital | York | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Boston Scientific Corporation |
United States, Australia, Belgium, Canada, Croatia, Germany, Italy, Singapore, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Rate of intent to treat subjects, randomized to PFA with PFA System inserted into body, during index procedure or repeat PFA procedure during blanking period, with device or procedure-related Composite Adverse Events that is serious. | Composite Adverse Events are defined as follows:
Day 0 through Day 7: Gastric motility / pyloric spasm disorders Heart block Myocardial infarction Peripheral or organ thromboembolism Pulmonary edema Stroke/ Cerebrovascular accident (CVA) Transient ischemic attack (TIA) Unresolved phrenic nerve palsy / paresis Vascular access complications Day 0 through Day 30: Cardiac tamponade / perforation Cardiovascular or pulmonary adverse event Death Pericarditis Day 0 through Month 12 Atrio-esophageal fistula Pulmonary vein stenosis |
12-Months | |
Primary | Rate of intent to treat subjects with treatment success from the pulse field ablation treatment and Anti-Arrhythmic Drug treatment. | Rate of Intent to Treat subjects with Treatment Success through Month 12 assessment
PFA Treatment Arm: Acute Success - Isolation of all attempted pulmonary veins and left atrial posterior wall with PFA system Chronic Success: Freedom from amiodarone use and after the blanking period through the Month-12 assessment occurrence of: Occurrence = 1 hour of asymptomatic or = 30 seconds of symptomatic Atrial Fibrillation (AF), Atrial Flutter (AFL), or Atrial Tachycardia (AT) Any re-ablation for AF, AFL, or AT Any electrical cardioversion for AF, AFL, or AT Any Class I or III AAD use AAD Treatment Arm: Acute Success - Ablation not performed during the blanking period Chronic Success - Freedom from amiodarone use and after the blanking period through the Month 12 assessment of occurrence of: Detectable occurrence = 1 hour of asymptomatic or = 30 seconds of symptomatic AF, AFL, or AT Electrical cardioversion for AF, AFL, or AT Any ablation for AF, AFL, or AT |
12-Months | |
Secondary | Atrial fibrillation burden between the pulsed field ablation and anti-arrhythmic drug arm, as measured by the LUX-Dx Insertable Cardiac Monitor and defined as the proportion of time an individual spends in AF during a period (expressed as a percentage). | Atrial Fibrillation (AF) burden, as measured by the LUX-Dx Insertable Cardiac Monitor (ICM) between the 2 randomized groups:
Pulsed Field Ablation (PFA) as initial treatment for subjects with persistent AF Anti-Arrhythmic Drug (AAD) as initial treatment for subjects with persistent AF AF Burden is defined as the proportion of time an individual spends in AF during a period (expressed as a percentage). |
12, 24, and 36 Months |
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