The VOLT AF First-in-Human (FIH) study will collect feasibility data to show that the Volt PFA System functions as intended in a clinical setting and to demonstrate acute safety and effectiveness for the treatment of symptomatic, recurrent…
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Source
Brief title
Condition
- Cardiac arrhythmias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Acute Safety:
Acute safety will be summarized as the rate of subjects experiencing a device
and/or procedure-related serious adverse event with onset within 7-days of any
ablation procedure (index or repeat procedure) that uses the Volt PFA System
that are defined below:
• Atrio-esophageal fistula1
• Cardiac tamponade/perforation2
• Death
• Heart block
• Myocardial infarction
• Pericarditis3
• Phrenic nerve injury resulting in permanent diaphragmatic paralysis
• Pulmonary edema
• Pulmonary vein stenosis1
• Stroke/cerebrovascular accident
• Thromboembolism
• Transient ischemic attack
• Vagal nerve injury/gastroparesis
• Vascular access complications (including major bleeding events4)
• Device and/or procedure related cardiovascular and/or pulmonary adverse event
that prolongs hospitalization for more than 48 hours (excluding hospitalization
solely for arrhythmia recurrence or non-urgent cardioversion)
Acute Effectiveness:
Acute procedural effectiveness will be summarized as the rate of pulmonary
veins treated with the Volt PFA system that are isolated at the end of the
index ablation procedure. Acute procedural failure for each pulmonary vein is
defined as any of the following:
1. Inability to isolate a pulmonary vein at the end of the index ablation
procedure. Isolation will be assessed via confirmation of electrical isolation
in each ablated pulmonary vein after a minimum waiting period of 20 minutes via
entrance block at a minimum. Touch-up ablation to achieve isolation will be
allowed for any pulmonary vein reconnection detected during the index procedure
with the investigational catheter (to the maximum delivery allowed per vein)
and will not be considered a failure.
2. Any use of a non-study ablation device for pulmonary vein isolation.
Secondary outcome
1. 12-month effectiveness: Freedom from documented (symptomatic or
asymptomatic) AF/AFL/AT episodes of >=30 seconds duration that are documented by
protocol-specified 12-lead ECG, transtelephonic monitoring (TTM) or Holter
monitor after the initial catheter ablation procedure through 12 months of
follow-up (after a 90-day blanking period following the initial ablation
procedure).
The situations in which subjects will be considered 12-month effectiveness
endpoint failures are those listed below:
• Acute procedural failure occurs, defined as the inability to isolate all
targeted pulmonary veins using only the Volt PFA Catheter for ablation.
Isolation will be assessed via confirmation of electrical isolation (via
entrance block at a minimum) in each ablated pulmonary vein after a minimum
waiting period of 20 minutes.
• Any use of a non-study ablation device for pulmonary vein isolation or to
deliver ablation lesions in the left atrium.
• If documented AF/AFL/AT recurrence (>30 second episode), excluding
cavotricuspid-dependent atrial flutter that has been confirmed in an
electrophysiology study (e.g. via entrainment maneuvers), occurs at any time
after the blanking period (>90 days after the initial procedure) as assessed by
protocol-specified 12-lead ECG, TTM, and Holter monitoring (NOTE: If the
subject has a continuous atrial arrhythmia throughout a 12-lead ECG recording
after the blanking period indicating AF/AFL/AT recurrence, this will be
considered sufficient documentation of recurrence unless there is evidence that
the recorded arrhythmia is short-lived and less than 30 seconds as determined
by the investigator.).
• If subject requires a repeat procedure for the treatment of AF,
non-CTI-dependent AFL, or AT using a non-study ablation device.
• Any use of a new class I or III AAD for AF after the blanking period.
• Any use of a class I or III AAD for AF at a dose higher than the historical
maximum dose for the subject.
• If the subject requires a cardioversion (electrical or pharmacological) for
the treatment of AF/AFL/AT after the blanking period (excluding CTI-dependent
AFL confirmed by entrainment maneuvers).
• Surgical treatment of AF/AFL/AT post index procedure.
AF/AFL/AT recurrence during the 90-day blanking period (<=90 days post-initial
procedure) will not be considered a treatment failure. One repeat procedure
for ablation of AF recurrence during the 90-day blanking period (performed
31-80 days post ablation) will not be considered a treatment failure so long as
the investigational PFA catheter is used for PVI ablation. Use of a
non-investigational catheter to achieve PVI or to deliver any additional
ablation lesions in the left atrium during the first repeat procedure will be
considered a treatment failure. A repeat procedure after the blanking period or
a second repeat procedure at any time will be considered a treatment failure.
After the 90-day blanking period, use of Class I or III antiarrhythmic drugs
(AADs) will not count as a treatment failure provided that only previously
failed AADs are taken at doses that do not exceed the previously failed dose.
AF/AFL/AT recurrence (for the purposes of assessing effectiveness endpoints)
will only be assessed by protocol-specified 12-lead ECG, TTM, and Holter
monitoring devices for assessment of this primary endpoint so that all subjects
are monitored equally with devices of the same sensitivity and specificity.
Collected ECG, TTM, and Holter data from sites will be evaluated by a physician
at a core laboratory for independent and unbiased assessment of AF/AFL/AT
recurrence for endpoint analysis.
2. Additional acute effectiveness measures:
a. Rate of pulmonary veins treated with the Volt PFA system that are isolated
at the end of the index ablation procedure when treated per protocol (to
isolation or to maximum allowable treatment applications).
b. Rate of subjects with procedural success of PVI ablation with the Volt PFA
System defined as in Section 4.1.2 in the PFA population and in the Per
Protocol population (defined in Section 8.1), where inability to isolate any
pulmonary vein would constitute a failure.
3. Proportion of subjects with successful first-pass isolation of all targeted
veins, and proportion of all targeted pulmonary veins with successful
first-pass PV isolation, where first pass isolation is defined as confirmation
of entrance block in the ablated pulmonary vein following the initial minimum
waiting period of 20 minutes without any ablation after the start of the
20-minute waiting period.
4. Proportion of subjects with reconnections, proportion of treated pulmonary
veins ablated with reconnections, and locations of pulmonary vein reconnections
(of treated veins) upon electro-anatomical remapping at 3 months.
5. Proportion of subjects that experience any procedure and/or Volt PFA
System-related adverse event (AE) throughout the 12-month follow-up period.
6. 12-month single procedure effectiveness, defined as 12-month effectiveness
as above after a single ablation procedure. Any repeat ablation procedure
required by the subject at any time will be deemed a failure.
7. Proportion of subjects requiring one or more repeat AF ablations at 12
months following the initial AF ablation procedure.
8. Changes in EQ-5D-5L and AFEQT scores from baseline to follow up at 3, 6, and
12-months after the initial procedure.
9. Procedure data, including but not limited to ablation data, mapping data,
usage of Automark, usage of the LivePoint, method(s) used for catheter
placement (e.g. fluoroscopy, intracardiac ultrasound, etc.), procedure time,
fluoroscopy time, total ablation time, LA dwell time, time to perform PVI, and
number and location of PFA energy applications.
10. Cardiovascular-related health care utilization through 12-months after the
initial procedure, including but not limited to, cardiovascular or AF-related
hospitalization (includes readmission) or emergency visit, cardioversion,
repeat ablations, use of AADs after 3-month blanking period, and primary SAEs.
11. Arrhythmia monitoring (12-lead ECG, HM, and TTM) compliance
12. Change in PV diameter from baseline to 30 days and 3 months post procedure.
13. Incidence, number, size (diameter and volume) and anatomic location of
cerebral lesions detected on post-procedure brain MRI compared to pre-procedure
brain MRI.
Background summary
AF is associated with mortality and comorbidities such as stroke, heart
failure, and sudden cardiac death. In a meta-analysis of contemporary,
well-controlled, randomized clinical trials in AF, the average annual stroke
rate was 1.5%, and annualized death rate was 3% in anticoagulated AF patients.6
A minority of these deaths are related to stroke, while sudden cardiac death
and death from progressive heart failure are more frequent, emphasizing the
need for interventions beyond anticoagulation.7, 8 Atrial fibrillation is also
associated with high rates of hospitalization. This hospitalization is commonly
for AF management, but is also often due to heart failure, myocardial
infarction, and treatment associated complications. 9, 10 Additionally,
patients with AF have significantly poorer quality of life than healthy
controls, experiencing a variety of symptoms including lethargy, palpitations,
dyspnea, chest pain, sleeping difficulties, and mental distress.10-14
The current conventional approach to perform catheter ablation is via thermal
energy such as cryoablation or radiofrequency (RF) energy to achieve pulmonary
vein isolation (PVI). However, there are many limitations to the current
standard of care ablation technologies, and even when PVI is performed at
highly experienced centers, reconnected PVs are observed in about 20% of
patients [ref]. Additionally, the reliance of these technologies on conductive
heating and cooling poses risks to organs or tissue adjacent to the heart which
can lead to adverse events such as, atrial-esophageal fistula, pulmonary vein
stenosis, phrenic nerve palsy, among others [ref]. Irreversible electroporation
(IRE) is a mechanism of inducing cell death via the application of pulsed
electric fields (PEF). Pulsed field ablation (PFA) utilizes IRE to selectively
destabilize cellular membranes to initiate cell death, resulting in a
non-thermal ablation lesion. Interestingly, myocardial tissue has a lower
voltage threshold susceptible to PFA when compared to surrounding tissues such
as the esophagus, blood vessels, and nerve fibers [ref], therefore reducing
risk of damage to these non-cardiac tissues and potentially lowering rates of
associated adverse events. In review of the current literature, studies/surveys
such as the IMPULSE/PEFCAT/PEFCAT II, PersAFOne, PULSED AF, 5S, and MANIFEST-PF
have shown PFA catheters are as safe or safer than other ablation
strategies.16-21 Additionally, none of the clinical trials reviewed found PFA
catheters to be less safe than the current standard ablation catheters. Each
PFA device currently in pre-clinical or clinical investigation are unique in
their electrode design, pulse length, pulse number, and voltage. These
parameters are critical in developing optimal PFA energy delivery for safe and
durable lesions. Thus far, all studies have shown high acute efficacy in
achieving PVI and a low rate of recurrent atrial arrhythmias.
With the growing burden of AF on the healthcare system and continued need for
increased safety and effectiveness in treatments, the Volt* PFA System has been
developed to deliver high-voltage therapy for the safe and effective treatment
of symptomatic recurrent AF.
Study objective
The VOLT AF First-in-Human (FIH) study will collect feasibility data to show
that the Volt PFA System functions as intended in a clinical setting and to
demonstrate acute safety and effectiveness for the treatment of symptomatic,
recurrent paroxysmal atrial fibrillation (PAF) and persistent atrial
fibrillation (PersAF).
Study design
.Pre-market, prospective, single-arm, non-randomized, multicenter
first-in-human clinical study
Intervention
Pulmonal Vein isolation (PVI) through Pulsed Field ablation (PFA)
Study burden and risks
Extensive risk analysis and risk mitigation plans will be implemented to
minimize any residual risk of the Volt* PFA Catheter, Sensor Enabled*, along
with the Volt* PFA Generator, Agilis* NxT Steerable Introducer Dual-Reach*, and
EnSite* X EP System EnSite* Pulsed Field Ablation Module and EnSite* X IDE
Display Workstation to subjects. The risks associated with Abbott*s Volt PFA
System are anticipated to be comparable to those associated with the use of
other commercially available ablation catheters approved for the treatment of
symptomatic recurrent PAF and PersAF. The patients participating in this study
are indicated for cardiac ablation for treatment of symptomatic recurrent PAF
or PersAF as part of their standard medical management and are subject to the
risks associated with these devices.
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Age
Inclusion criteria
1. Documented symptomatic PAF or PersAF. Documentation requirements are as
follows:
Paroxysmal:
• Physician*s note indicating recurrent self-terminating AF AND
• One electrocardiographically documented PAF episodes within 12 months.
Documented evidence of the PAF episode must either be continuous AF on a
12-lead ECG or include at least 30 seconds of AF from another ECG device.
Persistent: Continuous AF sustained beyond 7 days and less than 1 year that is
documented by
• Physician's note, AND either
• 24-hour Holter within 180-days prior to the procedure, showing continuous AF,
OR
• Two electrocardiograms (from any form of rhythm monitoring) showing
continuous AF:
o that are taken at least 7 days apart but less than 12 months apart
o If electrograms are more than 12 months apart, there must be one or
more Sinus Rhythm
recordings in between or within 12 months prior to
consent/enrollment
with the most recent electrocardiogram within 180 days of enrollment.
Documented evidence of the AF episode must either be continuous AF on a 12-lead
ECG or include at least 30 seconds of AF from another ECG device.
2. Plans to undergo a PVI catheter ablation procedure due to symptomatic PAF or
PersAF that is
refractory or intolerant to at least one Class I or III antiarrhythmic
drug
3. At least 18 years of age
4. Able and willing to comply with all trial requirements including
pre-procedure, post- procedure,
and follow-up testing and requirements
5. Informed of the nature of the trial, agreed to its provisions, and has
provided written informed
consent as approved by the Institutional Review Board/Ethics Committee
(IRB/EC) of the
respective clinical trial site.
Exclusion criteria
A patient will be excluded from enrollment in the clinical trial if he/she
meets any of the following criteria:
1. Previously diagnosed long-standing persistent atrial fibrillation (AF
greater than 1 year in
duration)
2. Arrhythmia due to reversible causes including thyroid disorders, acute
alcohol intoxication,
electrolyte imbalance, severe untreated sleep apnea, and other major
surgical procedures in
the preceding 90 days
3. Participant known to require ablation beyond PVI prior to initiating the
index procedure
4. Known presence of cardiac thrombus
5. Left atrial diameter >= 5.5 cm (anteroposterior diameter)
6. Left ventricular ejection fraction < 35% as assessed with echocardiography
within 180 days of
index procedure
7. New York Heart Association (NYHA) class III or IV heart failure
8. Body mass index > 40 kg/m2
9. Pregnant, nursing, or planning to become pregnant during the clinical
investigation follow-up
period
10. Patients who have had a ventriculotomy or atriotomy within the preceding 28
days of
procedure,
11. Myocardial infarction (MI), acute coronary syndrome, percutaneous coronary
intervention (PCI),
or valve or coronary bypass grafting surgery within preceding 90 days
12. Unstable angina
13. Stroke or TIA (transient ischemic attack) within the last 90 days
14. Heart disease in which corrective surgery is anticipated within 180 days
after procedure
15. History of blood clotting or bleeding abnormalities including
thrombocytosis, thrombocytopenia,
bleeding diathesis, or suspected anti-coagulant sate
16. Contraindication to long term anti-thromboembolic therapy
17. Patient unable to receive heparin or an acceptable alternative to achieve
adequate
anticoagulation
18. Known sensitivity to contrast media (if needed during the procedure) that
cannot be controlled
with pre-medication
19. Previous left atrial surgical or catheter ablation procedure (including LAA
closure device)
20. Presence of any condition that precludes appropriate vascular access
21. Severe mitral regurgitation (regurgitant volume >= 60 mL/beat, regurgitant
fraction >= 50%, and/or
effective regurgitant orifice area >= 0.40cm2).
22. Previous tricuspid or mitral valve replacement or repair
23. Patients with prosthetic valves
24. Patients with a myxoma
25. Patients with an interatrial baffle or patch as the transseptal puncture
could persist and produce
an iatrogenic atrial shunt
26. Stent, constriction, or stenosis in a pulmonary vein
27. Rheumatic heart disease
28. Hypertrophic cardiomyopathy
29. Diagnosed with amyloidosis or atrial amyloidosis
30. Active systemic infection
31. Renal failure requiring dialysis
32. Severe pulmonary disease (e.g., restrictive pulmonary disease, constrictive
or chronic
obstructive pulmonary disease) or any other disease or malfunction of
the lungs or respiratory
system that produces severe chronic symptoms
33. Presence of an implantable therapeutic cardiac device including permanent
pacemaker,
biventricular pacemaker, or any type of implantable cardiac
defibrillator (with or without
biventricular pacing function) or planned implant of such a device for
any time during the follow-
up period. Presence of an implantable loop recorder is acceptable as
long as it is removed prior
to insertion of the investigational device.
34. Presence of an implanted LAA closure device or plans to have an LAA closure
device
implanted during the follow-up period
35. Patient is currently participating in another clinical trial or has
participated in a clinical trial within
30 days prior to screening that may interfere with this clinical trial
without pre-approval from this
study Sponsor
36. Unlikely to survive the protocol follow up period of 12 months
37. Presence of other medical, anatomic, comorbid, social, or psychological
conditions that, in the
investigator*s opinion, could limit the subject*s ability to
participate in the clinical investigation or
to comply with follow-up requirements, or impact the scientific
soundness of the clinical
investigation results.
38. Individuals without legal authority
39. Individuals unable to read or write
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 |
|---|---|
| CCMO | NL82553.000.22 |