AntiPlatelet theraPy stratEgy followiNg left atrial appenDAGe closurE

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Bordeaux

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

3 Sep 2024 → ongoing

Decision date (initial)

2024-09-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515774-27-00

EudraCT number

2020-004263-84

ClinicalTrials.gov

NCT04796714

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy of 2 different antithrombotic strategies (aspirin VS aspirin + clopidogrel) following LAAC by comparing the occurrence of ischemic lesions on brain MRIs performed within 24h after the procedure (D0) and after 3 months of follow-up.

Secondary objectives 2

1. The impact of each therapeutic strategy carried out during 3 months on the occurrence : 1/ of death, 2/ symptomatic cerebral ischemic events (Symptomatic cerebral ischemic events), 3/ of all symptomatic systemic thromboembolic events, 4/ cerebral hemorrhagic events, 5/ systemic hemorrhagic events, 6/ deterioration of cognitive functions, 7/ of thrombus on prosthesis, 8/ residual leakage and endothelialization
2. The impact of the prosthesis implantation procedure itself on the occurrence of cardiac complications related to the procedure (pericardial effusion, ...)

Conditions and MedDRA coding

Atrial Fibrillation, atrial appendage, anticoagulants, stroke, platelet aggregation inhibitors

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male or female patients with LAAC indication according to CNEDiMTS guidelines
2. Age ≥ 18 years
3. Written informed consent provided by the patient
4. Heart team approval: multidisciplinary team including interventional cardiologists, neurologists and other physicians discussing the definitive contraindication for anticoagulation
5. Registration under social security system

Exclusion criteria 21

1. Minors
2. Unacceptable bleeding risk with double antiplatelet therapy decided by the physician who contraindicated oral anticoagulation
3. LAAC contraindication : left appendage thrombus
4. Major disease resulting in a life expectancy of < 1 year
5. Severe and inherited bleeding disorder
6. Known hypersensitivity to aspirin and/or clopidogrel - Hypersensitivity to clopidogrel, acetylsalicylic acid, or one of the excipients or other nonsteroidal anti-inflammatory drugs (crossreaction)
7. Known hypersensitivity to aspirin and/or clopidogrel - Asthma or a history of asthma with or without nasal polyps induced by salicyles or substances of close activity, including nonsteroidal antiinflammatory drugs
8. Known hypersensitivity to aspirin and/or clopidogrel - Evolving peptic ulcer or history of gastric hemorrhage or perforation after treatment with acetylsalicylic acid or other nonsteroidal antiinflammatory drugs
9. Known hypersensitivity to aspirin and/or clopidogrel - Any constitutional or acquired haemorrhagic disease
10. Known hypersensitivity to aspirin and/or clopidogrel - 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)
11. Known hypersensitivity to aspirin and/or clopidogrel - Severe liver failure
12. Known hypersensitivity to aspirin and/or clopidogrel - Severe kidney failure (Creatinine light < 30ml/min)
13. Known hypersensitivity to aspirin and/or clopidogrel - Uncontrolled severe heart failure
14. Contraindication to MRI: claustrophobia or inability to lie still for exam time, implantable pacemaker or defibrillator, intracorporeal metal foreign body (especially intraocular), intra-ocular metal clipcranial, cochlear implant, cardiac valve prosthesis type Starr-Edwards pre 6000, or biomedical device type insulin pump or neurostimulator.
15. Adults under legal protection (guardianship, curatorship or safeguard of justice)
16. Patient deprived of liberty by judicial or administrative decision,
17. Pregnant or breast-feeding women
18. Woman of childbearing age who does not benefit from highly effective contraception (CTFG recommendation on highly effective contraceptive methods: oral, intravaginal or transdermal estogeno-progestin contraception; progestin-based oral, injectable or implantable contraception; intrauterine device; hormonal intrauterine device; female sterilization (occlusion of the fallopian tubes))
19. Iode contraindication
20. Patient already participating in another category 1 interventional research
21. Patient in a period of exclusion relative to another research protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary end point is the number of ischemic lesions appearing on the diffusion sequences and/or FLAIR between cerebral MRI scans performed within 24 hours of the procedure and after 3 months of anti-thrombotic treatment.

Secondary endpoints 9

1. Symptomatic ischemic cerebral events (cerebral infarction and transient ischemic attacks) identified by MRI and systematic neurological examination at D1 and M3, and at any time in the event of a symptomatic event
2. Systemic thromboembolic events that will be identified when clinically symptomatic
3. Cerebral hemorrhagic events that will be identified by MRI (T2 sequence*) and by systematic neurological examination at D1 and M3, and at any time in the event of a symptomatic event.
4. Systemic bleeding events that will be identified when clinically symptomatic
5. Neurological deficits and their functional impact, which will be measured with the NIHSS (National Institute of Health Stroke Score) and by the modified Rankin score at each post-implantation assessment time (D1 and M3)
6. Cognitive assessment of patients using the Montreal Cognitive Assessment (MoCA) scale at D1 and M3
7. Events related to the prosthesis embolization procedure and severe pericardial effusion which will be objectified by clinical evaluation and ultrasound examination
8. The presence of thrombus on the prosthesis, the existence of residual leakage and the degree of endothelialization which will be evaluated by cardiac CT scan at 3 months
9. Treatment compliance will be assessed at M3 for all patients by accounting for treatments taken compared to those that should have been taken. This compliance will be correlated with thromboembolic and haemorrhagic events in order to define the accountability of the treatment strategy on these events

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Bordeaux

Sponsor organisation

Centre Hospitalier Universitaire De Bordeaux

Address

12 Rue Dubernat, Cs 91286 Cs 91286

City

Talence

Postcode

33400

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Dr Zakaria JALAL

Public contact point

Organisation

Centre Hospitalier Universitaire De Bordeaux

Contact name

Dr Zakaria JALAL

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications