Primary Objective: To obtain real world data on the use of, and provide continued evidence on safety and effectiveness of the FARAPULSE* Pulsed Field Ablation (PFA) system, when used per hospitals* standard of care.Secondary Objective: To understand…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The Primary Effectiveness Endpoints are:
Failure-free rate at 12 Month post index procedure.
Failure is defined as:
1. Not achieving Acute Success during index procedure
2. Not achieving Chronic Success
• After Blanking period (i.e., 90 days post-index procedure) until 12 Month
follow-up:
o Documented Atrial Fibrillation, or new onset of atrial flutter or
atrial tachycardia event (> 30 sec for any approved clinical arrhythmia
recording system, > 10 sec for 12-lead ECG)
o Interventions for Atrial Fibrillation, or new onset of atrial flutter
or atrial tachycardia event:
* Electrical and/or Pharmacological Cardioversion for AF/AFL/AT
* Repeat Procedures
* AV node ablation
* Administration of amiodarone (except intra-procedurally)
* Change in AAD medication: • Prescribed a higher dose of any AAD
documented at baseline, • Prescribed a new AAD not documented at baseline
The Primary Safety endpoints are:
1. Composite of the following device- or procedure-related SAEs:
• Early onset: Any of the following with an Onset Date within 7 days of the
Index procedure:
o Death
o Myocardial infarction
o Persistent phrenic nerve palsy
o Stroke
o Transient ischemic attack (TIA)
o Peripheral or organ (systemic) thromboembolism
o Cardiac tamponade / perforation
o Pericarditis
o Pulmonary edema
o Vascular access complications
o Heart block
o Gastric motility/pyloric spasm disorders
• Late onset: Either of the following with an Onset Date at any time through
the completion of 12 Month follow-up visit:
o Pulmonary vein stenosis (PVS)
o Atrio-esophageal fistula
2. All FARAPULSE* PFA procedure- and device related adverse events at 12 Month,
2 Year and 3 Year follow-up.
Secondary outcome
Additional Endpoints/analyses may include and are, not limited to the following:
• Failure-free rate from AF recurrence after blanking period to 12 Month
• Failure-free rate (as defined per section 6.2 in the protocol), assessed at
2 years and 3 years post index procedure
• Failure-free rate at 12 months, 2-years and 3-years post index procedure
between subjects off AAD after blanking period versus on AAD after blanking
period
• AF burden, defined as percentage of time spent in atrial arrhythmia,
assessed in the subset of subjects having any device (wearable or implantable)
capable of continuous monitoring of the heart rhythm
• Procedural Times, including but not limited to total procedure time
(defined as the recorded time of initiation of venous access to the recorded
time of venous access closure completion), total fluoroscopy time and dose and
LA dwell time (defined as the time between insertion of the first device into
the left atrium and removal of the last device from the left atrium)
• Rates of device- or procedure-related SAEs
• Assessment of operator variability and learning curve in different outcome
measures including: procedure times, acute procedural success, device- or
procedure-related SAEs and failure-free rate.
• Quality of Life using the following assessments:
o EuroQoL 5-Dimension 5-Level (EQ-5D-5L) Health Status Instrument -
required baseline versus 12 Month
o Atrial Fibrillation Effect on Quality of Life (AFEQT) Questionnaire -
required baseline versus 12 Month
• Analysis of study variables (e.g., Procedural workflow, procedural time)
for different countries, if needed
• Reconnection of Pulmonary veins during repeat procedure
• Number of applications performed per pulmonary vein
• Pain management
Background summary
1. Atrial Fibrillation
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia,
affecting approximately 2.2 million people in the United States and 4.5 million
in the European Union. The incidence increases with advancing age, affecting 6%
of the population over age 60 and 10% of the population over age 80. It is
estimated that the number of patients with AF in 2030 in Europe will be 14-17
million, and the number of new cases of AF per year at 120,000-215,000. In
Asia, the estimates prevalence of AF have suggested that, by 2050, 72 million
individuals in Asia will be diagnosed with AF, more than double the combined
numbers of patients in Europe and the United States. This estimate increase is
attributed to the proportionally larger aged population in Asian countries. AF
symptoms arise from the rapid, irregular rhythm as well as cardiac hemodynamic
changes related to uncoordinated atrial contractions. These uncoordinated
contractions also allow blood to pool in the atria and may ultimately lead to
thromboembolism and stroke. AF impairs quality of life, associates with a
five-fold risk of stroke, a three-fold incidence of congestive heart failure,
and higher mortality.
Atrial fibrillation remains a significant cause of morbidity and mortality in
industrialized societies. The annual risk of AF-related stroke is 5% per year
and one of every six strokes diagnosed occurs in the presence of AF. Therefore,
patients with AF require long-term anticoagulation to prevent embolic events.
Failure to manage AF may also lead to anatomic and electrical remodeling of the
left atrium, tachycardia-induced cardiomyopathy, and reduced left ventricular
function (heart failure). AF remains an extremely costly public health burden,
with annual per patient cost of care approaching approximately USD 3200 or
¤3000.
The Heart Rhythm Society (HRS) 2017 Consensus Statement on Catheter and
Surgical Ablation of Atrial Fibrillation as well as the European Society of
Cardiology (ESC) 2020 guidelines for the Diagnosis and Management of Atrial
Fibrillation, defines several different stages of AF based on its duration and
include:
• Paroxysmal AF (PAF): AF that terminates spontaneously or with intervention
within 7 days of onset
• Persistent AF (PersAF): continuous AF that is sustained beyond 7 days
• Long-standing PersAF: continuous AF of greater than 12 months* duration
In ESC, HRS, and JCS/JHRS guidelines catheter ablation is strongly recommended
for patients with symptomatic AF after an adequate trial of AAD therapy.
Several studies have demonstrated that AF catheter ablation is a safe and
superior alternative to anti-arrhythmic drugs (AADs) for maintenance of sinus
rhythm and symptom improvement. In particular, the isolation of the pulmonary
veins (PVI), where the majority of arrhythmogenic triggers is found, has been
shown to be a safe and effective technique to reduce arrhythmia recurrence and
related symptoms. Over the last 20 years PVI has remained the cornerstone
catheter ablation technique for AF ablation in subjects with recurrent and
symptomatic PAF refractory or intolerant to AADs. More recently, PVI for the
treatment of PAF is increasingly being performed as first line therapy, and
clinical evidence is accruing that this may well become an accepted first line
treatment.
2. Irreversible Electroporation
Al-Sakere 2007 described irreversible electroporation (IRE) as a non-thermal
tissue ablation technique in which intense short duration electrical fields are
used to permanently open pores in cell membranes, thus producing non-thermal
tissue ablation. Their study, using a mouse model, showed complete regression
in 92% of treated tumors. IRE ablation has a tissue-specific mechanism of
ablation. The tissue injury from IRE ablation occurs at the cellular level with
loss of homeostasis leading to necrosis or apoptosis. IRE ablation typically
spares the extracellular matrix, which facilitates rapid wound healing.
With respect to cardiac tissue, multiple studies have been described reporting
the effects of IRE in a porcine model. Across the studies, no stenosis was
observed at 3-weeks and 3-months of follow-up, and the lesion depth was further
characterized in the proximity of the phrenic nerve and coronary arteries, with
no damage to the adjacent structures or tissues noted. These animal studies
suggest that IRE can safely create deep lesions in heart tissue without harming
adjacent tissues.
3. FARAPULSE* Pulsed Field Ablation Study overview
The initial safety and feasibility human clinical studies of the FARAWAVE* PFA
Catheter were conducted in Europe in a paroxysmal atrial fibrillation (PAF)
population, including the IMPULSE, PEFCAT, and PEFCAT II trials. All studies
supported the safety and feasibility of the FARAPULSE* PFA System using the
FARAWAVE* PFA Catheter in the treatment of patients with PAF, with a low rate
of acute and long-term primary safety endpoint events and a high rate (100%) of
acute procedural success resulting in CE Mark approval for the treatment of PAF
in early 2021.
The randomized ADVENT Trial (A Prospective Randomized Pivotal Trial of the
FARAPULSE* PFA System Compared with Standard of Care Ablation in Patients with
Paroxysmal Atrial Fibrillation) is being conducted in the United States to
establish the safety and effectiveness of the FARAPULSE* PFA System using the
FARAWAVE* PFA Catheter in a drug refractory symptomatic PAF patient population.
Subjects in the study are either randomized to catheter ablation with the
FARAPULSE* PFA system or conventional thermal ablation (radiofrequency or
cryoballoon ablation). The data will be used to gain initial market approval of
the FARAPULSE* PFA System using the FARAWAVE* PFA Catheter in the US for the
PAF population.
The FARA FREEDOM study, a Post Market Clinical Follow-up study, is being
conducted in Europe, with the objective to provide ongoing demonstration of
safety and performance of the FARAPULSE* Pulsed Field Ablation system in the
treatment of subjects with Paroxysmal Atrial Fibrillation. Approximately 180
subjects will be enrolled and followed for 1 year.
In addition, the ADVANTAGE-AF study is an IDE pivotal study utilizing the
FARAPULSE* Pulsed Field Ablation system in the treatment of subjects with
persistent atrial fibrillation. This IDE is being conducted in the United
States, Europe and Asia and will enroll approximately 339 treated subjects,
followed for 1 year.
Study objective
Primary Objective:
To obtain real world data on the use of, and provide continued evidence on
safety and effectiveness of the FARAPULSE* Pulsed Field Ablation (PFA) system,
when used per hospitals* standard of care.
Secondary Objective:
To understand the effect of Pulsed Field Ablation treatment on Quality of Life
from the general population indicated for a treatment with PFA in a real-world
setting.
Study design
The FARADISE study is an observational, prospective, non-randomized,
single-arm, multi-center post-market study.
All subjects signing the informed consent, undergoing the index procedure and
being treated with the study device, will be followed-up for 3 years.
Each subject will be followed at specific time point after index procedure: at
pre-discharge, 3 Month, 6 Month (Phone call only), 12 Month (in-clinic visit
mandatory), 24 Month (2 Year) and 36 Month (3 Year) after index procedure. It
is recommended to perform the 3 Month, 2 Year and 3 Year Follow-up visit
in-clinic. The study duration for each treatment subject is expected to be
approximately 3 years. Study enrollment is expected to be completed in
approximately 18 months. Treatment subjects will be followed for 3 years.
Finally, study closure is expected to take an additional 6 months. In total,
the study duration is expected to be 5 years.
Study burden and risks
Patients who take part in this study are subject to similar risks shared by all
patients who have an ablation procedure but are not in this study.
Lambroekstraat (Green Square) 5D
Diegem 1831
BE
Lambroekstraat (Green Square) 5D
Diegem 1831
BE
Listed location countries
Age
Inclusion criteria
1. Subjects intended to be treated with the FARAPULSE* Pulsed Field Ablation
system for cardiac tissue ablation, per physician*s medical judgement, and as
per hospitals* standard of care
2. Subjects who are willing and capable of providing informed consent
3. Subjects who are willing and capable of participating in all testing
associated with this clinical study at an approved clinical investigational
center
4. 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
1. Subjects with a current interatrial baffle or patch
2. Subjects with a known or suspected atrial myxoma
3. Subjects with a myocardial infarction within 14 days prior to enrollment
4. Subjects with a recent (within 30 days prior to enrollment) Cerebral
Vascular Accident (CVA)
5. Subjects who do not tolerate anticoagulation therapy
6. Subjects with an active systemic infection
7. Subjects with a presence of atrial known thrombus
8. Subjects with a known inability to obtain vascular access
9. Subjects who are pregnant or planning to be pregnant
10. Subjects with atrial fibrillation that is secondary to electrolyte
imbalance, thyroid disease, alcohol, or other reversible / non-cardiac causes
11. Subjects with any prosthetic heart valve, ring or repair including balloon
aortic valvuloplasty
12. Subjects with a contraindication to an invasive electrophysiology procedure
where insertion or manipulation of a catheter in the cardiac chambers is deemed
unsafe per physician*s medical judgement, such as, but not limited to, a recent
previous cardiac surgery (e.g., ventriculotomy or atriotomy, CABG,
PTCA/PCI/coronary stent procedure/unstable angina) and/or in patients with
congenital heart disease where the underlying abnormality increases the risk of
the ablation (e.g., severe rotational anomalies of the heart or great vessels)
13. Subjects with a life expectancy of <= 1 year per investigator*s opinion
14. 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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05501873 |
| CCMO | NL82863.100.23 |