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NCT Number: NCT05353140

LAAO Versus NOAC in Patients with AF and PCI

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.

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Key information

Conditions

Atrial Fibrillation Arrhythmias, Cardiac Cardiovascular Diseases Heart Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Percutaneous Coronary Intervention

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ling Tao

Xi'an, Shannxi, 710032, China

Location status: Recruiting

Location contact

Chao Gao

CONTACT

[email protected]

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Successful PCI for unstable angina or CCS
  • Non-valvular atrial fibrillation
  • Concomitant at least one of the following conditions: congestive heart failure, hypertension, ≥65yrs, diabetes, previous stroke, TIA or thromboembolism
  • Eligible for long-term novel oral anti-coagulation (NOAC) therapy
  • 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:

  • Under the age of 18
  • Unable to give informed consent or currently participating in another trial and not yet at its primary endpoint
  • 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)
  • Concurrent medical condition with a life expectancy of less than 3 years
  • Haemodynamical unstable
  • Known contraindication to medications such as heparin, antiplatelet or anticoagulation drugs, or contrast
  • 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
  • Known contraindication to LAAO or LAAO is not required
  • Comorbidities other than atrial fibrillation that required long term use of anticoagulation (such as implanted a mechanical valve)
  • 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)
  • Ongoing overt bleeding
  • Previous stroke/TIA within 30 days of enrolment
  • Symptomatic carotid artery disease
  • Severe renal insufficiency (CrCl≤30ml/min)

Imaging Exclusion Criteria:

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

Treatment and study plan

The WATCHMAN/WATCHMAN FLX device

Device

Watchman device was an umbrella-shaped, self-expanding, nitinol structure with a porous partial polyethylene terephthalate membrane (160 um mesh) and 10 struts. The membrane portion of the structure faces into the body of the left atrial to block embolization of thrombus and provide scaffolding on which endothelialization can occur. The On July 21st, 2020, the FDA approved the next generation LAAO device, named Watchman FLX. This newiteration of the Watchman LAAO platform offers full capability of recapture and redeployment of the device, decreasedmetallic exposure, an increased number of contact points for sealing, a fully rounded delivery shape, and precision anchors designed to provide optimal device engagement with the LAA.

Rivaroxaban + Clopidogre

Drug

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. In the present study, Rivaroxaban + Clopidogre are required for 45 days in LAAO group after LAAO.

Aspirin + clopidogrel

Drug

Aspirin + Clopidogrel are required from 46 days to 12 months after LAAO.

Primary outcomes

  1. Major adverse cardiac and cerebrovascular events (MACCE)

    Time frame: 12 months

    MACCE define as a composite endpoint of any death, any stroke, any myocardial infarction (MI), and systemic embolism (SE).

Secondary outcomes

  1. BARC type 2, 3 or 5 bleeding events

    Time frame: 36 months

    Powered Key secondary endpoint, Bleeding Academic Research Consortium (BARC) defined type 2, 3, 5 bleeding events

Other outcomes

  1. BARC type 2, 3 or 5 bleeding events

    Time frame: 45days, 3, 6, 12, 24, 60months

    Bleeding Academic Research Consortium (BARC) defined type 2, 3, 5 bleeding events

  2. BARC type 3 or 5 bleeding events

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Bleeding Academic Research Consortium (BARC) defined type 3, 5 bleeding events

  3. BARC type 2 bleeding events

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Bleeding Academic Research Consortium (BARC) defined type 2 bleeding events

  4. A composite endpoint of any death, any stroke, and systemic embolism

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    A composite endpoint of any death, any stroke, and systemic embolism

  5. Any death

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Any death

  6. Any stroke

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Any stroke

  7. Any myocardial infarction (MI)

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Any myocardial infarction (MI)

  8. Systemic embolism (SE)

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Systemic embolism (SE)

  9. Target lesion failure (TLF)

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Target lesion failure (TLF), defined as the composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically indicated target lesion revascularization (TLR), and its individual components

  10. Patient oriented Composite Endpoint (PoCE)

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Patient oriented Composite Endpoint (PoCE), defined as the composite of any death, any myocardial infarction, any stroke, any revascularization, and systemic embolism, and its individual components

  11. Net adverse clinical events (NACE)

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Net adverse clinical events (NACE), defined as the composite of any death, any myocardial infarction, any stroke, any revascularization, systemic embolism, and BARC type 3 or 5 bleeding events and its individual components

  12. Acute/subacute/early thrombosis

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Acute, subacute, or early thrombosis

  13. TIMI major bleeding and/or minor bleeding

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Thrombolysis in Myocardial Infarction (TIMI) defined major bleeding and/or minor bleeding

  14. ISTH major bleeding and/or clinically relevant minor bleeding

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    International Society on Thrombosis and Haemostasis (ISTH) defined major bleeding and/or clinically relevant minor bleeding

  15. Device/Technical/Procedural successful rate

    Time frame: 30 days post LAAO

    Device success was defined as the device deployed and implanted in the correct position. Technical success was defined as the exclusion of the left atrial appendage, with no device-related complications and no leak >5 mm. Procedural success was defined as technical success and no procedure-related complications

  16. Procedure related major complications

    Time frame: 30 days post LAAO

    Defined according to the the Munich consensus document on definitions, endpoints, and data collection requirements for LAAO clinical studies

  17. Patient adherence to allocated medication

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Patient adherence to allocated medication, defined as the use of medication strategies of this trial on 80% of the time in therapeutic range

  18. Neurological assessment

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Neurological assess by modified Rankin Scale (mRS) score: The mRS is used to assess long-term function following a stroke event. Complete a mRS Stroke Assessment Worksheet at approximately 90 days following the stroke for a long-term functional assessment. Scores: 0, No symptoms; 1, No significant disability. Able to carry out all usual activities, despite some symptoms; 2, Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; 3, Moderate disability. Requires some help, but able to walk unassisted; 4, Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; 5, Severe disability. Requires constant nursing care and attention, bedridden, incontinent; 6, Dead.

  19. Neurological assessment

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Neurological assess by NIH Stroke Scale (NIHSS) score: The NIHSS is an acute stroke assessment tool used to assess stroke severity, with a score of 0-42. The higher the score, the more severe the neurological deficit. NIHSS score ≤ 4 should be considered mild strokes, and ≥ 21 should be considered severe strokes. An NIHSS should be completed at baseline and within 24-48 hours of the stroke event during follow-up for urgent assessment of stroke severity. If there is a change or abnormality of NIHSS, a neurologist consultation is required to determine whether the increase in the corresponding score compared to the previous visit is due to neurological reasons.

  20. Quality of life assessments

    Time frame: 45days, 3, 6, 12, 24, 36, 60months

    Quality of life assess by Five-level EuroQol five-dimensional questionnaire (EQ-5D-5L): EQ-5D-5L is a simple and general health measurement method. In the description part, the health status will be described in 5 dimensions. The questionnaire require subjects to choose the most suitable option for themselves from each dimension according to their health status. The visual analog scale section is on a vertical scale, recording subjects' self-assessed health status.

Study contacts

Contact information is provided by the study sponsor or research team.

Chao Gao, M.D., Ph.D.

CONTACT

[email protected]

+86-18629551066

Ruining Zhang, BSc

CONTACT

[email protected]

+86-15802990370

Sponsors and collaborators

Lead sponsor

Xijing Hospital

Other

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2028
Study completion
2029
First posted
Apr 29, 2022
Registry last updated
Mar 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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