AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE (APPENDAGE)

University Hospital of Bordeaux

Status and phase: Enrolling; Phase 4

Conditions: Atrial Fibrillation; Stroke; Anticoagulants; Platelet Aggregation Inhibitors; Atrial Appendage

Treatments: Drug: Double antiplatelet therapy; Drug: Aspirin; Device: Brain MRI; Other: Neurological tests

Study type: Interventional

Funder types: Other

Identifiers

NCT04796714

CHUBX 2017/29

Details and patient eligibility

About

The APPENDAGE study is a phase 4 multicentre randomized opened clinical trial comparing 2 different antithrombotic strategies following left atrial appendage closure (LAAC) in patients with non valvular atrial fibrillation (AF). The primary objective of the study is to evaluate the efficacy of Aspirin versus Aspirin + Clopidogrel after LAAC by comparing the occurrence of ischemic lesions on cerebrovascular magnetic resonance imaging (MRI) studies.

Full description

Atrial fibrillation (AF) is the most common sustained arrhythmia and increases the risk of ischemic stroke. Although oral anticoagulation (OAC) is recommended in patients with CHADS2VA2SC score ≥ 1, this medication is associated with severe haemorrhagic complications. Several trials showed that percutaneous LAAC with the Watchman device (Boston Scientific, Natick, Massachusetts) or the Amplatzer Cardiac Plug (ACP) /Amulet device (St. Jude Medical, Minneapolis, Minnesota) was shown to be non-inferior but also superior as compared to warfarin in preventing the combined outcome of stroke, systemic embolism, and cardiovascular death. Therefore, LAAC has become an integral part of treatment guidelines in AF patients.

However, the post procedural management of antithrombotic therapy in these patients remains a challenge, as bleeding risk needs to be balanced against risk for thrombus formation on the device and thromboembolic complications. After LAAC, various antithrombotic protocols have been proposed by different teams but the optimal postprocedural antithrombotic medication and its duration are still debated. The Investigators recently showed in a prospective registry that LAAC using ACP devices followed by a single antiplatelet therapy could be a reasonable alternative for stroke prevention in patients with high bleeding risk.

The APPENDAGE study is a phase 4 multicentre randomized opened clinical trial comparing 2 different antithrombotic strategies (aspirin versus aspirin + clopidogrel) following LAAC. The primary objective of the study is to evaluate the efficacy of these 2 strategies after LAAC by comparing the occurrence of ischemic lesions on cerebrovascular MRI studies performed immediately after the procedure (D 0) and after 3 months of follow-up.

Enrollment: 60 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female patients with LAAC indication according to "Commission nationale d'évaluation des dispositifs médicaux et des technologies de santé" (CNEDiMTS) (National Commission for the Evaluation of Medical Devices and Health Technologies) guidelines
• Age ≥ 18 years
• Written informed consent provided by the patient
• Heart team approval: multidisciplinary team including interventional cardiologists, neurologists and other physicians discussing the definitive contraindication for anticoagulation
• Registration under social security system

Exclusion criteria

• Minors

• Unacceptable bleeding risk with double antiplatelet therapy decided by the physician who contraindicated oral anticoagulation

• LAAC contraindication : left appendage thrombus

• Major disease resulting in a life expectancy of < 1 year

• Severe and inherited bleeding disorder

• Known hypersensitivity to aspirin and/or clopidogrel:

  • Hypersensitivity to clopidogrel, acetylsalicylic acid, or one of the excipients or other nonsteroidal anti-inflammatory drugs (cross-reaction).
  • Asthma or a history of asthma with or without nasal polyps induced by salicylates or substances of close activity, including nonsteroidal anti-inflammatory drugs.
  • Evolving peptic ulcer or history of gastric hemorrhage or perforation after treatment with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs.
  • Any constitutional or acquired haemorrhagic disease.
  • Patients with mastocytosis, in whom the use of acetylsalicylic acid can lead to severe hypersensitivity reactions (including circulatory shocks with flushing, hypotension, tachycardia and vomiting).
  • Severe liver failure.
  • Severe kidney failure (Creatinine light < 30ml/min).
  • Uncontrolled severe heart failure

• Contraindication to MRI: claustrophobia or inability to lie still for exam time, implantable pacemaker or defibrillator, intracorporeal metal foreign body (especially intraocular), intracranial metal clip, cochlear implant, cardiac valve prosthesis type Starr-Edwards pre 6000, or biomedical device type insulin pump or neurostimulator.

• Guardianship

• Curatorship

• Pregnancy or child-bearing potential female

• Woman of childbearing age who does not benefit from highly effective contraception (CTFG recommendation on highly effective contraceptive methods: oral, intravaginal or transdermal estrogeno-progestin contraception; progestin-based oral, injectable or implantable contraception; intrauterine device; hormonal intrauterine device; female sterilization (occlusion of the fallopian tubes))

• Iode contraindication

• Patient already participating in another category 1 interventional research

• Patient in a period of exclusion relative to another research protocol.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Double antiplatelet therapy group

Sham Comparator group

Description:

Patient randomized in this group will receive 1 tablet containing clopidogrel 75 mg and 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.

Treatment:

Other: Neurological tests

Drug: Double antiplatelet therapy

Device: Brain MRI

Aspirin group

Experimental group

Description:

Patients randomized in this group: will receive 1 bag containing aspirin 160 mg as treatment. This treatment will start on the day of LAAC procedure and continued for 3 months.

Treatment:

Other: Neurological tests

Drug: Aspirin

Device: Brain MRI