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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
One sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months
One sachet of aspirin 160 mg per day during 3 months
Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).
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)
Bordeaux University Hospital
Pessac, France
RECRUITINGToulouse University Hospital
Toulouse, France
NOT_YET_RECRUITINGChange 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.
Time frame: Baseline and 3 months
Occurrence of symptomatic cerebral ischaemic events
Number of cerebral infarctions and transient ischaemic attacks identified by MRI and systematic neurological examination at D1 and M3, and at any time in the event of a symptomatic event.
Time frame: From day 1 to month 3
Occurrence of systemic thromboembolic events
Number of systemic thromboembolic events that will be identified when clinically symptomatic
Time frame: From day 1 to month 3
Occurrence of cerebral haemorrhagic events
Number of cerebral haemorrhagic events that will be identified by MRI and by systematic neurological examination at D0 and M3, and at any time in the event of a symptomatic event
Time frame: From day 0 to month 3
Occurence of systemic bleeding events
Number of systemic bleeding events that will be identified when clinically symptomatic
Time frame: 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
It will be measured by the NIHSS scale score. Values range from 0 to 42. Score 1 to 4: minor stroke, 5 to 15 : moderate stroke, 15 to 20 : severe stroke, \> 20 : severe stroke
Time frame: Day 1 and month 3
Assessment by the Modified Rankin Score of the functional impact of ischaemic and/or haemorrhagic strokes
It will be measured by the Modified Rankin Score. Values range from 0 (no symptoms) to 5 (severe disability)
Time frame: Day 1 and month 3
Cognitive assessment by the Montreal Cognitive Assessment (MoCA) scale
Patients cognitive assessment will be performed using the Montreal Cognitive Assessment (MoCA) scale score. Values range from 0 to 30. A score of 26 is considered normal.
Time frame: Day 1 and Month 3
Occurrence of procedural related complications
The number of procedural related complications (device embolization, significant pericardial effusion) will be assessed by physical examination and transthoracic echocardiography
Time frame: From day 0 to month 3
Occurence of device-related thrombus, persistence of a residual leak and endothelialisation process
The number of device-related thrombus, persistence of a residual leak and endothelialisation process will be assessed by cardiac computed tomography (CT)
Time frame: Month 3
Counting of treatments taken
Compliance will be assessed for all patients by counting the number of treatments taken versus those that should have been taken. This compliance will be correlated with thromboembolic and hemorrhagic events to define the imputability of the therapeutic strategy on these events.
Time frame: Month 3
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