AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE

NCT ID: NCT04796714

Last Updated: 2022-10-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-03
• Study Completion Date: 2024-05-03

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Double antiplatelet therapy group

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.

Group Type: SHAM_COMPARATOR

Double antiplatelet therapy

Intervention Type: DRUG

One sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months

Brain MRI

Intervention Type: DEVICE

Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).

Neurological tests

Intervention Type: OTHER

Neurological assessment with the implementation of the modified rankin, National Institute of Health Stroke Score (NIHSS), and Montreal Cognitive Assessment (MoCA) tests (D1 and M3)

Aspirin group

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.

Group Type: EXPERIMENTAL

Aspirin

Intervention Type: DRUG

One sachet of aspirin 160 mg per day during 3 months

Brain MRI

Intervention Type: DEVICE

Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).

Neurological tests

Intervention Type: OTHER

Neurological assessment with the implementation of the modified rankin, National Institute of Health Stroke Score (NIHSS), and Montreal Cognitive Assessment (MoCA) tests (D1 and M3)

Interventions

Double antiplatelet therapy

One sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months

Intervention Type: DRUG

Aspirin

One sachet of aspirin 160 mg per day during 3 months

Intervention Type: DRUG

Brain MRI

Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).

Intervention Type: DEVICE

Neurological tests

Neurological assessment with the implementation of the modified rankin, National Institute of Health Stroke Score (NIHSS), and Montreal Cognitive Assessment (MoCA) tests (D1 and M3)

Intervention Type: OTHER

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Bordeaux

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Zakaria JALAL, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Bordeaux

Antoine BENARD, MD

Role: STUDY_CHAIR

University Hospital, Bordeaux

Locations

Bordeaux University Hospital

Pessac, , France

Site Status: RECRUITING

Toulouse University Hospital

Toulouse, , France

Site Status: NOT_YET_RECRUITING

Countries

France

Central Contacts

Zakaria JALAL, MD

Role: CONTACT

zakaria.jalal@chu-bordeaux.fr

(0)5 57 65 64 65 ext. +33

Amandine RUISSEL

Role: CONTACT

amandine.ruissel@chu-bordeaux.fr

(0)5 57 62 32 29 ext. +33

Facility Contacts

Zakaria JALAL, MD

Role: primary

zakaria.jalal@chu-bordeaux.fr

(0)5 57 79 56 79 ext. +33

Amandine RUISSEL

Role: backup

amandine.ruissel@chu-bordeaux.fr

(0)5 57 62 32 29 ext. +33

Meyer ELBAZ, MD-PhD

Role: primary

elbaz.m@chu-toulouse.fr

(0)5 61 32 33 25 ext. +33

Other Identifiers

CHUBX 2017/29

Identifier Type: -

Identifier Source: org_study_id