Atrial FibrillationPhase 4APPENDAGENCT04796714
AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE
A Phase 4 study testing Double antiplatelet therapy, Aspirin and Brain MRI in people with Atrial Fibrillation and Atrial Appendage, run by University Hospital, Bordeaux at 2 sites in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atrial Fibrillation, Atrial Appendage, Anticoagulants
- What is being tested?
- Double antiplatelet therapy, Aspirin and Brain MRI
- Type of treatment
- Pill or oral medicine, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 2 sitesFrance
- Study dates
- 3 Oct 2022to 3 May 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 22Show fewer
- 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 locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France2 sites, 2 recruiting
- Recruiting
Bordeaux University Hospital
Pessac, 33604
Zakaria JALAL, MD, (0)5 57 79 56 79 ext. +33, zakaria.jalal@chu-bordeaux.fr
Amandine RUISSEL, (0)5 57 62 32 29 ext. +33, amandine.ruissel@chu-bordeaux.fr
- Not yet recruiting
Toulouse University Hospital
Toulouse, 31059
Meyer ELBAZ, MD-PhD, (0)5 61 32 33 25 ext. +33, elbaz.m@chu-toulouse.fr
Meyer ELBAZ, MD-PhD
About this study
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.
Read the 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
- Being tested
- Double antiplatelet therapy, Aspirin, Brain MRI, Neurological tests
- Keywords
- left atrial appendage, percutaneous closure, stroke, antiplatelet therapy, atrial fibrillation
- Medical subject headings
- Atrial Fibrillation, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Double antiplatelet therapyDrug
One sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months
AspirinDrug
One sachet of aspirin 160 mg per day during 3 months
Brain MRIDevice
Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).
Neurological testsOther
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)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Aspirin; Device: Brain MRI; Other: Neurological tests |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 3 months
Secondary outcomes (10)
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.
Measured: From day 1 to month 3
Occurrence of systemic thromboembolic events
Number of systemic thromboembolic events that will be identified when clinically symptomatic
Measured: 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
Measured: From day 0 to month 3
Occurence of systemic bleeding events
Number of systemic bleeding events that will be identified when clinically symptomatic
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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
Measured: 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)
Measured: 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.
Measured: Month 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start3 Oct 2022
- Primary completion3 May 2027 (estimated)
- Study completion3 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by University Hospital, BordeauxThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zakaria JALAL, MD, Principal investigator, University Hospital, BordeauxAntoine BENARD, MD, Study chair, University Hospital, Bordeaux
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04796714
- Sponsor's protocol ID
- CHUBX 2017/29
- Other IDs
- 2020-004263-84
- Acronym
- APPENDAGE
- Status last verified
- Oct 2025
- First submitted
- 8 Mar 2021
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Cochet H, Iriart X, Sridi S, Camaioni C, Corneloup O, Montaudon M, Laurent F, Selmi W, Renou P, Jalal Z, Thambo JB. Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study. Eur Heart J Cardiovasc Imaging. 2018 Dec 1;19(12):1351-1361. doi: 10.1093/ehjci/jey010.
PubMed 29415203
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE
- ClinicalTrials.gov ID
- NCT04796714
- Acronym / sponsor ID
- APPENDAGE / CHUBX 2017/29
- Conditions
- Atrial Fibrillation, Atrial Appendage, Anticoagulants, Stroke, Platelet Aggregation Inhibitors
- Keywords
- left atrial appendage, percutaneous closure, stroke, antiplatelet therapy, atrial fibrillation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Study start
- 3 Oct 2022 (actual)
- Primary completion
- 3 May 2027 (estimated)
- Study completion
- 3 May 2027 (estimated)
- First posted
- 15 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Double antiplatelet therapy group | Sham comparator | Drug: Double antiplatelet therapy, Device: Brain MRI, Other: Neurological testsPatient 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. |
| Aspirin group | Experimental | Drug: Aspirin, Device: Brain MRI, Other: Neurological testsPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Double antiplatelet therapyOne sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months | Drug | Double antiplatelet therapy group |
| AspirinOne sachet of aspirin 160 mg per day during 3 months | Drug | Aspirin group |
| Brain MRITwo cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90). | Device | Aspirin group, Double antiplatelet therapy group |
| Neurological testsNeurological assessment with the implementation of the modified rankin, National Institute of Health Stroke Score (NIHSS), and Montreal Cognitive Assessment (MoCA) tests (D1 and M3) | Other | Aspirin group, Double antiplatelet therapy group |
Primary outcome
Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans
Time frame: Baseline and 3 months
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.
10 secondary outcomes
Occurrence of symptomatic cerebral ischaemic events
Time frame: From day 1 to month 3
Occurrence of systemic thromboembolic events
Time frame: From day 1 to month 3
Occurrence of cerebral haemorrhagic events
Time frame: From day 0 to month 3
Occurence of systemic bleeding events
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
Time frame: Day 1 and month 3
Assessment by the Modified Rankin Score of the functional impact of ischaemic and/or haemorrhagic strokes
Time frame: Day 1 and month 3
Cognitive assessment by the Montreal Cognitive Assessment (MoCA) scale
Time frame: Day 1 and Month 3
Occurrence of procedural related complications
Time frame: From day 0 to month 3
Occurence of device-related thrombus, persistence of a residual leak and endothelialisation process
Time frame: Month 3
Counting of treatments taken
Time frame: Month 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Results publication: PubMed 29415203Cochet H, Iriart X, Sridi S, Camaioni C, Corneloup O, Montaudon M, Laurent F, Selmi W, Renou P, Jalal Z, Thambo JB. Left atrial appendage patency and device-related thrombus after percutaneous left atrial appendage occlusion: a computed tomography study. Eur Heart J Cardiovasc Imaging. 2018 Dec 1;19(12):1351-1361. doi: 10.1093/ehjci/jey010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zakaria JALAL, MD principal investigator
University Hospital, Bordeaux
Antoine BENARD, MD study chair
University Hospital, Bordeaux
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Double antiplatelet therapy, Aspirin and Brain MRI in people with Atrial Fibrillation and Atrial Appendage, run by University Hospital, Bordeaux at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zakaria JALAL, MD ((0)5 57 65 64 65 ext. +33, zakaria.jalal@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans (time frame: Baseline and 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04796714, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.