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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06096337




Registration number
NCT06096337
Ethics application status
Date submitted
17/10/2023
Date registered
23/10/2023
Date last updated
25/06/2024

Titles & IDs
Public title
Pulsed Field Ablation (PFA) Versus Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation
Scientific 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
Secondary ID [1] 0 0
PF303
Universal Trial Number (UTN)
Trial acronym
AVANT GUARD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent Atrial Fibrillation 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Devices - FARAPULSE™ Pulsed Field Ablation (PFA) System
Treatment: Drugs - Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, and Dofetilide

Experimental: Pulsed Field Ablation (PFA) - Pulsed Field Ablation (PFA) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)

Active comparator: Anti-Arrhythmic Drug (AAD) - Anti-Arrhythmic Drug (AAD) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)


Treatment: Devices: FARAPULSE™ Pulsed Field Ablation (PFA) System
Subjects will undergo a pulsed field ablation procedure using the FARAPULSE™ Pulsed Field Ablation (PFA) System for the isolation of pulmonary veins and posterior wall.

Treatment: Drugs: Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, and Dofetilide
Anti-Arrhythmic Drugs (AADs) including, Flecainide, Sotalol, Propafenone, and Dofetilide will be prescribed and monitored in accordance with local clinical practice and already established guideline-directed therapy for patients with persistent atrial fibrillation (AF).
Intervention code [1] 0 0
Treatment: Devices
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12-Months
Primary outcome [2] 0 0
Rate of intent to treat subjects with treatment success from the pulse field ablation treatment and Anti-Arrhythmic Drug treatment.
Timepoint [2] 0 0
12-Months
Secondary outcome [1] 0 0
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).
Timepoint [1] 0 0
12, 24, and 36 Months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
NA
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
28/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/12/2027
Actual
Sample size
Target
387
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [2] 0 0
Monash Medical Centre - Clayton
Recruitment postcode(s) [1] 0 0
4032 - Chermside
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
State/province [4] 0 0
California
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Michigan
Country [13] 0 0
United States of America
State/province [13] 0 0
Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
New Hampshire
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oklahoma
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Rhode Island
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Utah
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Belgium
State/province [27] 0 0
Brugge
Country [28] 0 0
Canada
State/province [28] 0 0
Ontario
Country [29] 0 0
Canada
State/province [29] 0 0
Quebec
Country [30] 0 0
Canada
State/province [30] 0 0
Vancouver
Country [31] 0 0
Croatia
State/province [31] 0 0
Split
Country [32] 0 0
Germany
State/province [32] 0 0
Frankfurt
Country [33] 0 0
Italy
State/province [33] 0 0
AN
Country [34] 0 0
Italy
State/province [34] 0 0
MI
Country [35] 0 0
Italy
State/province [35] 0 0
RA
Country [36] 0 0
Singapore
State/province [36] 0 0
Singapore
Country [37] 0 0
Spain
State/province [37] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boston Scientific Corporation
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT06096337
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Oussama Wazni, M.D.
Address 0 0
The Cleveland Clinic
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Boston Scientific
Address 0 0
Country 0 0
Phone 0 0
800-272-1001
Fax 0 0
Email 0 0
monitortroubleshooting@cdxbsci.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06096337