AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE

NCT04796714 | Unknown Phase 4 DMC

• 1 other identifier: CHUBX 2017/29
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

left atrial appendage; percutaneous closure; stroke; antiplatelet therapy; atrial fibrillation

Outcome Measures

Primary Outcomes (1)

• Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans

  Assessment of number of ischaemic lesions appearing on diffusion sequences and/or (Fluid Attenuated Inversion Recovery) FLAIR between cerebral MRI scans at D0 after implantation and after 3 months of antithrombotic treatment. The interpretation of the MRI scans will be centralised and carried out by an independent Corelab in the neuro radiology imaging department of Bordeaux University Hospital. These analyses will be carried out by two independent radiologists. In the event of disagreements or inconsistent values, a third review will be carried out by a third independent radiologist. The final value of the different variables will be reduced to the average of these 2 or 3 interpretations.

  Baseline and 3 months

Secondary Outcomes (10)

• Occurrence of symptomatic cerebral ischaemic events

  From day 1 to month 3

• Occurrence of systemic thromboembolic events

  From day 1 to month 3

• Occurrence of cerebral haemorrhagic events

  From day 0 to month 3

• Occurence of systemic bleeding events

  From day 1 to month 3

• Assessment by the NIHSS scale (National Institute of Health Stroke Score) of the functional impact of ischaemic and/or haemorrhagic strokes

  Day 1 and month 3

Study Arms (2)

Double antiplatelet therapy group

SHAM COMPARATOR

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.

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

Aspirin group

EXPERIMENTAL

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.

Drug: Aspirin; Device: Brain MRI; Other: Neurological tests

Interventions

Double antiplatelet therapy DRUG

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

Double antiplatelet therapy group

Aspirin DRUG

One sachet of aspirin 160 mg per day during 3 months

Aspirin group

Brain MRI DEVICE

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

Aspirin group; Double antiplatelet therapy group

Neurological tests 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; Double antiplatelet therapy group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Bordeaux: lead

Study Sites (2)

Bordeaux University Hospital

Pessac, 33604, France

RECRUITING

Toulouse University Hospital

Toulouse, 31059, France

NOT YET RECRUITING

MeSH Terms

Conditions

Atrial Fibrillation; Stroke

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Zakaria JALAL, MD

  University Hospital, Bordeaux

  PRINCIPAL INVESTIGATOR

• Antoine BENARD, MD

  University Hospital, Bordeaux

  STUDY CHAIR

Central Study Contacts

Zakaria JALAL, MD

CONTACT

(0)5 57 65 64 65; zakaria.jalal@chu-bordeaux.fr

Amandine RUISSEL

CONTACT

(0)5 57 62 32 29; amandine.ruissel@chu-bordeaux.fr

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2021
• First Posted: March 15, 2021
• Study Start: October 3, 2022
• Primary Completion: May 3, 2024
• Study Completion: May 3, 2024
• Last Updated: October 17, 2022

Record last verified: 2022-10

Locations

FR (2)