The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pulsed Field Ablation (PFA) Versus Anti-Arrhythmic Drug (AAD) Therapy as a First Line Treatment for Persistent Atrial Fibrillation (AVANT GUARD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT06096337
Recruitment Status : Recruiting
First Posted : October 23, 2023
Last Update Posted : April 8, 2024
Sponsor:
Information provided by (Responsible Party):
Boston Scientific Corporation

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Persistent Atrial Fibrillation Device: FARAPULSE™ Pulsed Field Ablation (PFA) System Drug: Anti-Arrhythmic Drug (AAD): Flecainide, Sotalol, Propafenone, and Dofetilide Not Applicable

Detailed Description:

This is a prospective, randomized, multi-center, global, pivotal Investigational device exemption (IDE) study. Subjects with persistent atrial fibrillation will be randomized to either pulsed field ablation (PFA) or Versus Anti-Arrhythmic Drug (AAD) treatment.

Subjects randomized to PFA treatment will undergo percutaneous ablative pulmonary vein isolation (PVI) and left atrial posterior wall isolation (PWI) using the FARAWAVE™ PFA Catheter (first-line ablation cohort).

Subjects randomized to AAD treatment will be prescribed and monitored in accordance with local clinical practice and already established guideline-directed therapy for patients with persistent atrial fibrillation (AF). Cardioversion is recommended during the initiation of antiarrhythmic drugs for subjects who are not in sinus rhythm. In the case of clinical inefficacy, the AAD dose will be up-titrated to the maximum tolerated dose. Thereafter, a change to a second or to a third AAD should be undertaken, insofar as the subject remains within the blanking period, with the goal to completely suppress AF episodes ≥ 30 seconds in duration. It is advisable to perform cardioversion with each dose titration or when changing the AAD regimen. If AAD treatment is proven to be ineffective or intolerable outside of the blanking period, subjects can undergo subsequent ablation therapy and be considered part of the "delayed ablation cohort".

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 387 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : December 28, 2023
Estimated Primary Completion Date : December 25, 2025
Estimated Study Completion Date : December 30, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Dofetilide

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Pulsed Field Ablation (PFA)
Pulsed Field Ablation (PFA) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)
 Device: 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.
Active Comparator: Anti-Arrhythmic Drug (AAD)
Anti-Arrhythmic Drug (AAD) is used as the initial treatment for subjects with persistent atrial fibrillation (AF)
 Drug: 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).


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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. [ Time Frame: 12-Months ]

    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

  2. Rate of intent to treat subjects with treatment success from the pulse field ablation treatment and Anti-Arrhythmic Drug treatment. [ Time Frame: 12-Months ]

    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


Secondary Outcome Measures :
  1. 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). [ Time Frame: 12, 24, and 36 Months ]

    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).



Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06096337


Contacts
Layout table for location contacts
Contact: Boston Scientific 800-272-1001 monitortroubleshooting@cdxbsci.com
Contact: Boston Scientific 866-484-3268

Locations
Show Show 50 study locations
Sponsors and Collaborators
Boston Scientific Corporation
Investigators
Layout table for investigator information
Principal Investigator: Oussama Wazni, M.D. The Cleveland Clinic
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Boston Scientific Corporation
ClinicalTrials.gov Identifier: NCT06096337    
Other Study ID Numbers: PF303
First Posted: October 23, 2023    Key Record Dates
Last Update Posted: April 8, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Boston Scientific Corporation:
Persistent Atrial Fibrillation
Insertable Cardiac Monitor
Pulsed Field Ablation
 Atrial Fibrillation
Cardiovascular Diseases
Heart Diseases
Additional relevant MeSH terms:
Layout table for MeSH terms
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Flecainide
Sotalol
Propafenone
Anti-Arrhythmia Agents
Dofetilide
Voltage-Gated Sodium Channel Blockers
Sodium Channel Blockers
 Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Potassium Channel Blockers