Clinical trial NCT05353140: LAAO Versus NOAC in Patients with AF and PCI
Official title: Left Atrial Appendage Occlusion Versus Novel Oral Anti-coagulation in Patients with Atrial Fibrillation and Percutaneous Coronary Intervention: a Randomized, Multicentre, Open-label, Non-inferiority Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Atrial Fibrillation
Percutaneous Coronary Intervention
Keywords: Left atrial appendage occlusion
Percutaneous coronary intervention
Novel oral anti-coagulation
Atrial Fibrillation
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2022-04-29
Enrollment: 1386
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Atrial fibrillation (AF) coincides with coronary artery disease (CAD) shared common risk factors and pathophysiologic pathways. CAD affects approximately 25% of AF patient according to the trial Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), while in the Global Registry of Acute Coronary Events (GRACE) atrial fibrillation affected about 9% of patients with CAD. It is reported that approximately 5-8% of the patients who underwent PCI had concomitated atrial fibrillation.

For AF patients who underwent PCI, both antiplatelet and antithrombotic medications are required for preventing stent thrombosis and ischemic stroke, leading to an increased risk of bleeding. Finding a safe and effective balance between the risk of ischaemic events and bleeding complications is challenged by the shared risk factors for either event such as advanced age, congestive heart failure, hypertension, diabetes, previous stroke, etc..

Previous pivotal trials have shown that in patients with atrial fibrillation and requiring antiplatelet treatment, a NOAC plus clopidogrel regimen was associated with a lower incidence of bleeding events as compared with a warfarin-based triple antithrombotic strategy. Therefore, the current expert opinions and consensus of North American Societies recommend a NOAC plus a P2Y12 inhibitor in patients with AF and PCI. However, the NOAC plus clopidogrel strategy still led to 16.8% of clinically significant bleeding (PIONEER AF-PCI). Consequently, the compliance of OAC/NOAC is commonly suboptimal among PCI patients who require an antithrombotic strategy for AF.

Percutaneous left atrial appendage occlusion (LAAO) is a non-pharmacological strategy for stroke prevention in patients with AF. Both randomized data and registries have confirmed it can be an alternative to oral anticoagulation in patients with nonvalvular AF. Current guidelines recommend LAAO for patients with NVAF who have contraindications or are unsuitable for long-term OAC.

Considering the unique high risk of AF patients with PCI, LAAO may be an attractive treatment option by obviating the need for combined oral anticoagulation and antiplatelet therapy. However, so far there is no data from neither randomized cohorts nor real-world registries showing if LAAO can be a safe and effective alternative strategy compared to VKA/NOAC for stroke prevention in AF patients who underwent PCI. The PROTECT AF and PREVAIL studies showed that the percutaneous LAAO was non-inferior to warfarin therapy, and the PRAGUE-17 trial showed non-inferior to direct oral anticoagulants, however, the small sample size of these trials limited further subgroup analyses of the PCI sub-population. In the NCDR registry, which is the largest cohort of LAAO up to now, 20.3% of the LAAO patients had a prior myocardial infarction. However, the proportion of stent implantation was not reported. Among previous trials, the proportion of patients with coronary artery disease ranged from 28.5% to 47.5%. The large number of AF patients with CAD warrant the optimal stroke prevention strategy to be assessed in this population.

The primary goal of the proposed study is to investigate if the non-inferiority would be met for the LAAO when compared to NOACs in NVAF patients with PCI in terms of a composite endpoint of any death, any stroke, any myocardial infarction, systemic embolism at 12 months. In addition, the powered key secondary will also have 80% of power to show superiority for the LAAO when compared to NOACs in terms of BARC type 2, 3, or 5 bleeding events at 36 months.


Eligibility criteria: Inclusion Criteria:

1. Successful PCI for unstable angina or CCS
2. Non-valvular atrial ﬁbrillation
3. Concomitant at least one of the following conditions: congestive heart failure, hypertension, ≥65yrs, diabetes, previous stroke, TIA or thromboembolism
4. Eligible for long-term novel oral anti-coagulation (NOAC) therapy
5. Able to understand and provide informed consent and comply with all study procedures/medications

Exclusion Criteria:

Patients who meet any of the following criteria will be disqualified from participation in the study:

Clinical exclusion criteria:

1. Under the age of 18
2. Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
3. Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential according to local practice)
4. Concurrent medical condition with a life expectancy of less than 3 years
5. Haemodynamical unstable
6. Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
7. PCI for ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI), or experienced a peri-procedural myocardial infarction (MI) caused by PCI
8. Known contraindication to LAAO or LAAO is not required
9. Comorbidities other than atrial ﬁbrillation that required long term use of anticoagulation (such as implanted a mechanical valve)
10. The patient had or is planning to have any cardiac (excluding the current PCI procedure) or non-cardiac interventional or surgical procedure within 30 days prior to or 60 days after the WATCHMAN device implant (e.g., cardioversion, ablation, cataract surgery)
11. Ongoing overt bleeding
12. Previous stroke/TIA within 30 days of enrolment
13. Symptomatic carotid artery disease
14. Severe renal insufficiency (CrCl≤30ml/min)

Imaging Exclusion Criteria:

1. Left atrial appendage (LAA) thrombus
2. High risk patent foramen ovale or atrial septal defect requiring invasive treatment
3. Anatomical unsuitable for LAAO
4. Rheumatic heart valve disease, mitral valve stenosis (valve area \<1.5cm2)

Primary outcomes:
measure: Major adverse cardiac and cerebrovascular events (MACCE)
timeFrame: 12 months
Secondary outcomes:
measure: BARC type 2, 3 or 5 bleeding events
timeFrame: 36 months
Other outcomes:
measure: BARC type 2, 3 or 5 bleeding events
timeFrame: 45days, 3, 6, 12, 24, 60months
measure: BARC type 3 or 5 bleeding events
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: BARC type 2 bleeding events
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: A composite endpoint of any death, any stroke, and systemic embolism
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Any death
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Any stroke
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Any myocardial infarction (MI)
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Systemic embolism (SE)
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Target lesion failure (TLF)
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Patient oriented Composite Endpoint (PoCE)
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Net adverse clinical events (NACE)
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Acute/subacute/early thrombosis
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: TIMI major bleeding and/or minor bleeding
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: ISTH major bleeding and/or clinically relevant minor bleeding
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Device/Technical/Procedural successful rate
timeFrame: 30 days post LAAO
measure: Procedure related major complications
timeFrame: 30 days post LAAO
measure: Patient adherence to allocated medication
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Neurological assessment
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Neurological assessment
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
measure: Quality of life assessments
timeFrame: 45days, 3, 6, 12, 24, 36, 60months
Locations:
city: Xi'an
country: China
facility: Ling Tao
state: Shannxi
Study officials:
affiliation: Xijing Hospital
name: Ling Tao, M.D., Ph.D.
role: STUDY_CHAIR
affiliation: Xijing Hospital
name: Chao Gao, M.D., Ph.D.
role: STUDY_CHAIR
References: