The primary objective of this study is to establish the safety and effectiveness of the WATCHMAN TM Left Atrial Appendage Closure (LAAC) Device including the post-implant medication regimen for subjects with non-valvular atrial fibrillation who are…
ID
Source
Brief title
Condition
- Cardiac arrhythmias
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The occurrence of one of the following events between the time of implant and
within 7 days following the procedure or by hospital discharge, whichever is
later: all-cause death, ischemic stroke, systemic embolism, or device- or
procedure- related events requiring open cardiac surgery or major endovascular
intervention such as pseudoaneurysm repair, AV fistula repair, or other major
endovascular repair. Percutaneous catheter drainage of pericardial effusions,
percutaneous retrieval of an embolized device, thrombin injection to treat
femoral pseudoaneurysm and nonsurgical treatments of access site complications
are excluded from this endpoint
Secondary outcome
1. The time to first occurrence of stroke (including ischemic and/or
hemorrhagic), cardiovascular death (cardiovascular and/or unexplained cause)
and systemic embolism
2. The time to first occurrence of major bleeding (defined as a BARC type 3 or
5 event)
3. The time to first occurrence of non-procedure related major bleeding
(defined as a BARC type 3 or 5 event)
4. Non-disabling vs. disabling and fatal stroke analysis as defined using VARC-2
5. The time to occurrence of cardiovascular death (cardiovascular and/or
unexplained cause)
6. The time to occurrence of all-cause death
7. The time to first occurrence of all-cause stroke (ischemic and/or
hemorrhagic)
8. The time to first occurrence of hemorrhagic stroke
9. Procedural success defined as a completed WATCHMAN implant procedure with no
primary safety endpoint and no device embolization.
10. Rates of effective (defined as jet size of <=5mm) and complete (defined as
no peri-device flow) LAA closure at 3 and 12 months post implant.
Background summary
Atrial fibrillation (AF) is one of the most common abnormal rhythm disturbances
and affects
approximately 5.5 million people worldwide, including 10% of people older than
75 years.
The most debilitating consequence of AF is thrombus formation from stagnant
blood flow
leading to thromboembolism and stroke. As such, the rate of ischemic stroke
attributed to
non-valvular AF is estimated to average 5% per year, which is 2-7 times that of
those without
AF.2
Treatment with warfarin therapy for the prevention of thromboemboli originating
in the left
atrial appendage has been well documented. Warfarin therapy targeting an
International
Normalized Ratio (INR) between 2.0 - 3.0 has been considered the gold standard
treatment
historically for patients with non-valvular AF for prevention of stroke. While
warfarin has
remained the optimum treatment for many years, there are numerous challenges
with the
drug, such as frequent need for monitoring and dosage adjustments, dietary and
metabolic
interactions, and concerns of patient compliance. Additionally, the potential
for frequent and
fatal bleeding are high concerns for patients and caregivers, and often it is
found this drug is
not well tolerated.
Currently available alternatives to warfarin are the direct oral anticoagulants
(DOACs),
which include dabigatran, rivaroxaban, apixaban, and edoxaban. Unlike warfarin,
DOACs
can be administered without the need for monitoring, have fewer food and drug
interactions,
and provide an improved effectiveness/safety ratio. Dabigatran at the dose of
150 mg twice
daily is shown to be superior to warfarin in prevention of stroke and systemic
thromboembolism, has a favorable safety profile including significantly less
intracranial
bleeding and comparable extracranial bleeding, and is associated with less
cardiovascular
mortality. Rivaroxaban at a daily dose of 20 mg is shown to be non-inferior to
warfarin in
prevention of stroke or systemic embolism. The risk of major bleeding is not
significantly
different for rivaroxaban versus warfarin; however, intracranial and fatal
bleeding is less
frequent with rivaroxaban. In comparison to warfarin, apixaban at a dose of 5
mg twice
daily is also shown to be superior in prevention of stroke and systemic
thromboembolism,
causes less bleeding, and is associated with a lower mortality rate. Edoxaban
is shown to be
non-inferior to warfarin with respect to the prevention of stroke or systemic
embolism, and is
associated with significantly lower rates of bleeding and death from
cardiovascular causes.
While these direct agents, and warfarin, are effective and safe in their
intended patient
populations, there are patients who, based on a determination of benefit and
risk, cannot
tolerate exposure to systemic anticoagulation with these agents even for a
short period of
time.
As the risk of stroke increases with age and the disability and tolerance
concerns with
available drug therapy persist, the need for permanent protection against
thromboembolism
in AF patients remains unmet. The sponsor has developed the WATCHMAN® Left
Atrial
Appendage Closure (LAAC) Device, a permanent implantable device to seal off the
left atrial
appendage, the location where the vast majority of thrombi originate in AF
patients. This
device has been shown to provide an alternative to warfarin therapy in
non-valvular AF
patients who require thromboembolic protection.
The WATCHMAN LAAC Device has primarily been studied with the post implant drug
regimen consisting of: 45-days of warfarin, followed by dual antiplatelet
therapy (DAPT)
until 6-months post-implant, followed by indefinite single antiplatelet therapy
of aspirin.
Several studies have been conducted that look at alternative post-implant drug
regimens
which exclude warfarin, including 6-months DAPT followed by stand-alone aspirin
and 6-
weeks of DAPT followed by stand-alone aspirin. The ASAP Feasibility trial and
the
EWOLUTION and WASP registries utilized the WATCHMAN device with post procedure
DAPT . Other LAA closure devices have
utilized post procedure DAPT consisting of clopidogrel for 1 to 6 months and
aspirin 100 mg
for at 5 months. Early data suggest that shortened DAPT may be acceptable for
subjects
that can*t take oral anticoagulants.
The current study is designed to collect data for the WATCHMAN LAA Closure
Device, in
subjects with non-valvular AF who are unable to take oral anticoagulants, even
for a short
period of time.
Study objective
The primary objective of this study is to establish the safety and
effectiveness of the WATCHMAN TM Left Atrial Appendage Closure (LAAC) Device
including the post-implant medication regimen for subjects with non-valvular
atrial fibrillation who are deemed not to be eligible for anti-coagulation
therapy to reduce the risk of stroke. The device is intended to reduce the risk
of thromboembolic ischemic stroke and systemic embolism.
Study design
This study is a prospective, randomized, multi-center, global investigation to
determine the safety and effectiveness of the WATCHMAN Device for subjects with
non-valvular atrial fibrillation who are deemed not suitable for
anti-coagulation therapy to reduce the risk of stroke.
Intervention
No concomitant procedures are to be performed at the time of the WATCHMAN
implant procedure. This includes, but is not limited to, cardiac ablation
procedures, transcutaneous valve procedures, cardioversions, coronary stent,
pacemaker or ICD generator change, etc.
Study burden and risks
Additional risks that are associated with implanting the WATCHMAN TM Device
include:
• misplacement of the Device
• dislodgement of the Device in your heart if it does not fit properly, which
could lead to a procedure or major surgery to remove the Device
• the inability to place the Device in the correct position or inability to
remove the Device if necessary
• excessive bleeding
• Device infection
• allergic reaction to the implant materials
• blood clots on the Device
• Device fracture
• scarring or clotted veins
• the Device may not properly close off your LAA
• inability to implant the Device
Lambroekstraat (Green Square) 5D
Diegem 1831
BE
Lambroekstraat (Green Square) 5D
Diegem 1831
BE
Listed location countries
Age
Inclusion criteria
1. The subject is of legal age to participate in the study per the laws of their respective geography.
2. The subject has documented paroxysmal, persistent, permanent or long-term/longstanding persistent non-valvular atrial fibrillation (i.e., the subject has not been diagnosed with rheumatic mitral valvular heart disease).
3. The subject has a calculated CHA2DS2-VASc score of 2 or greater.
4. The subject is deemed by two study physicians to be unsuitable for oral anticoagulation.
5. The subject is deemed by a study physician to be suitable for the defined protocol pharmacologic regimen of aspirin and clopidogrel* therapy following WATCHMAN Closure Device implant.
6. The subject or legal representative is able to understand and willing to provide written informed consent to participate in the trial.
7. The subject is able and willing to return for required follow-up visits and examinations.
Exclusion criteria
1. The subject is unable or unwilling to return for required follow-up visits and examinations.
2. The subject had or is planning to have any invasive cardiac procedure within 30 days prior to randomization (e.g., cardioversion, ablation).
3. The subject is planning to have any cardiac or non-cardiac invasive or surgical procedure that would necessitate stopping or modifying the protocol required medication regimen within 90 days after the WATCHMAN Closure Device implant (e.g., cardioversion, ablation, cataract surgery).
4. The subject had a prior stroke (of any cause) or TIA within the 30 days prior to randomization.
5. The subject had a prior BARC type 3 or 4 bleeding event within the 14 days prior to randomization. Lack of resolution of related clinical sequelae, or planned and pending interventions to resolve bleeding/bleeding source, are a further exclusion regardless of timing of the bleeding event.
6. The subject has a history of atrial septal repair or has an ASD/PFO device.
7. The subject has an implanted mechanical valve prosthesis in any position.
8. The subject suffers from New York Heart Association Class IV Congestive Heart Failure.
9. The subject has LVEF < 30%.
10. The subject is of childbearing potential and is, or plans to become pregnant during the time of the study (method of assessment upon study physician*s discretion).
11. The subject is 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 should be brought to the attention of the sponsor to determine eligibility.
12. The subject has a life expectancy of less than two years.
13. The subject has a known or suspected hypercoagulable state.
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 | NL61037.100.17 |