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AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE (APPENDAGE)

Primary Purpose

Atrial Fibrillation, Atrial Appendage, Anticoagulants

Status
Recruiting
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
Double antiplatelet therapy
Aspirin
Brain MRI
Neurological tests
Sponsored by
University Hospital, Bordeaux
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring left atrial appendage, percutaneous closure, stroke, antiplatelet therapy, atrial fibrillation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Bordeaux University HospitalRecruiting
  • Toulouse University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Sham Comparator

Experimental

Arm Label

Double antiplatelet therapy group

Aspirin group

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Occurrence of systemic thromboembolic events
Number of systemic thromboembolic events that will be identified when clinically symptomatic
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
Occurence of systemic bleeding events
Number of systemic bleeding events that will be identified when clinically symptomatic
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
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)
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.
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
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)
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.

Full Information

First Posted
March 8, 2021
Last Updated
October 13, 2022
Sponsor
University Hospital, Bordeaux
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1. Study Identification

Unique Protocol Identification Number
NCT04796714
Brief Title
AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE
Acronym
APPENDAGE
Official Title
AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 3, 2022 (Actual)
Primary Completion Date
May 3, 2024 (Anticipated)
Study Completion Date
May 3, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Bordeaux

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atrial Fibrillation, Atrial Appendage, Anticoagulants, Stroke, Platelet Aggregation Inhibitors
Keywords
left atrial appendage, percutaneous closure, stroke, antiplatelet therapy, atrial fibrillation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Double antiplatelet therapy group
Arm Type
Sham Comparator
Arm 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.
Arm Title
Aspirin group
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Double antiplatelet therapy
Intervention Description
One sachet of aspirin 160 mg and one tablet of clopidogrel 75 mg per day.during 3 months
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
One sachet of aspirin 160 mg per day during 3 months
Intervention Type
Device
Intervention Name(s)
Brain MRI
Intervention Description
Two cerebral Magnetic Resonance Imaging (MRI) examinations will be carried out (D0 and D90).
Intervention Type
Other
Intervention Name(s)
Neurological tests
Intervention Description
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)
Primary Outcome Measure Information:
Title
Change from baseline of ischaemic lesions number at 3 months appearing on brain MRI scans
Description
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
Secondary Outcome Measure Information:
Title
Occurrence of symptomatic cerebral ischaemic events
Description
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
Title
Occurrence of systemic thromboembolic events
Description
Number of systemic thromboembolic events that will be identified when clinically symptomatic
Time Frame
From day 1 to month 3
Title
Occurrence of cerebral haemorrhagic events
Description
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
Title
Occurence of systemic bleeding events
Description
Number of systemic bleeding events that will be identified when clinically symptomatic
Time Frame
From day 1 to month 3
Title
Assessment by the NIHSS scale (National Institute of Health Stroke Score) of the functional impact of ischaemic and/or haemorrhagic strokes
Description
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
Title
Assessment by the Modified Rankin Score of the functional impact of ischaemic and/or haemorrhagic strokes
Description
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
Title
Cognitive assessment by the Montreal Cognitive Assessment (MoCA) scale
Description
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
Title
Occurrence of procedural related complications
Description
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
Title
Occurence of device-related thrombus, persistence of a residual leak and endothelialisation process
Description
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
Title
Counting of treatments taken
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Zakaria JALAL, MD
Phone
(0)5 57 65 64 65
Ext
+33
Email
zakaria.jalal@chu-bordeaux.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Amandine RUISSEL
Phone
(0)5 57 62 32 29
Ext
+33
Email
amandine.ruissel@chu-bordeaux.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zakaria JALAL, MD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antoine BENARD, MD
Organizational Affiliation
University Hospital, Bordeaux
Official's Role
Study Chair
Facility Information:
Facility Name
Bordeaux University Hospital
City
Pessac
ZIP/Postal Code
33604
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zakaria JALAL, MD
Phone
(0)5 57 79 56 79
Ext
+33
Email
zakaria.jalal@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Amandine RUISSEL
Phone
(0)5 57 62 32 29
Ext
+33
Email
amandine.ruissel@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Zakaria JALAL, MD
First Name & Middle Initial & Last Name & Degree
Jean-Benoit THAMBO, MD-PhD
First Name & Middle Initial & Last Name & Degree
Xavier IRIART, MD
First Name & Middle Initial & Last Name & Degree
Hubert COCHET, MD-PhD
First Name & Middle Initial & Last Name & Degree
Pauline RENOU, MD
First Name & Middle Initial & Last Name & Degree
Igor SIBON, MD-PhD
Facility Name
Toulouse University Hospital
City
Toulouse
ZIP/Postal Code
31059
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meyer ELBAZ, MD-PhD
Phone
(0)5 61 32 33 25
Ext
+33
Email
elbaz.m@chu-toulouse.fr
First Name & Middle Initial & Last Name & Degree
Meyer ELBAZ, MD-PhD
First Name & Middle Initial & Last Name & Degree
Pierre MONDOLY, MD

12. IPD Sharing Statement

Learn more about this trial

AntiPlatelet theraPy stratEgy followiNg Left Atrial appenDAGe closurE

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