Avoiding Anticoagulation After IntraCerebral Haemorrhage

Atrial Fibrillation Clinical Trial

— A3ICH  

Official title:

Avoiding Anticoagulation After IntraCerebral Haemorrhage

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03243175
• Other study ID #: 2016_77
• Secondary ID: 2017-004371-31
• Status: Recruiting
• Phase: Phase 3
• Start date: January 24, 2019
• Est. completion date: December 2026

Study information

• Verified date: January 2023
• Source: University Hospital, Lille
• Contact: Charlotte Cordonnier, MD, PhD
• Phone: 3 20 44 68 14
• Email: charlotte.cordonnier[@]chru-lille.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomised controlled trials (RCTs) demonstrate a substantial benefit from oral anticoagulant drugs for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation (AF). However, these RCTs excluded patients with prior intracerebral haemorrhage (ICH). Therefore, guidelines are unable to recommend whether oral anticoagulant drugs, in particular non-vitamin K antagonist (called direct OAC) - can be used for patients with AF after an intracerebral haemorrhage. Roughly 30% of adults with ICH have AF but in 2017 it remains unclear whether they should start oral anticoagulant drugs, be treated with left atrial appendage closure (LAAC) or avoid anticoagulation and LAAC.

Description:

Open label randomised controlled multicentre clinical trial with masked outcome assessment (PROBE design) comparing 3 strategies (1:1:1): anticoagulation with a Direct OAC (Apixaban 5mgx2/day) vs avoid anticoagulation with left atrial appendage closure (LAAC) compared to usual care (avoid anticoagulation). Primary outcome: the net clinical benefit (composite outcome of major ischaemic and haemorrhagic events) during a follow-up of 24 months (adjudication committee masked to the randomisation arm The results of A3ICH will help the clinician to decide which strategy is the most effective in terms of benefit/risk ratio to prevent the risk of stroke or systemic embolism in patients with a history of ICH and AF. A3ICH will address this increasingly common dilemma and could affect clinical practice. Data from A3ICH will contribute to an international individual patient data meta-analysis.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria

• Adult (older than 18 years old, no upper age limit)
• with a history of paroxysmal, persistent or long-standing non-valvular atrial fibrillation (documented on an electrocardiogram)
• and a CHA2DS2VASc score of 2 or more who have an indication for long-term anticoagulation
• who suffered from a spontaneous intracerebral haemorrhage (while being treated with oral anticoagulants or not) documented with brain CT or MRI
• more than 14 days before randomization (no upper delay limit)
• for whom there is a clinical equipoise regarding the choice of the best preventive strategy to avoid future vascular events. Exclusion criteria for all treatment groups
• Pre-randomisation modified Rankin score of 4 or 5
• Conditions other than atrial fibrillation for which the patient requires long term anticoagulation (for example prosthetic mechanical heart valve)
• Serious bleeding events within the 6 months before randomisation (except for intracerebral haemorrhage)
• Life expectancy of less than 1 year
• Pregnancy or breastfeeding Exclusion criteria related to the LAAC only
• Contraindications due to local, anatomical reasons (such as thrombus in the left atrial appendage, infection with a risk of endocarditis)
• Patients older than 85 years
• CHA2DS2VASc score of 2 or 3
• Patient or attending physician are unwilling to undergo/perform intervention for LAAC Exclusion criteria related to the Direct OAC only
• Chronic renal insufficiency (clearance of creatinine by Cockcroft method < 30ml/min)
• Body weight lower than 50 kg
• Allergy to apixaban
• Coexisting conditions predisposing to head trauma (e.g. gait disturbances, uncontrolled seizures disorders)
• Patient or attending physician are unwilling to use of Direct OAC

Related Conditions & MeSH terms

• Atrial Fibrillation
• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage
• Microhaemorrhage

Intervention

Drug:
• Apixaban 5 MG
Apixaban 5mg x 2 during 24 months

Device:
• left atrial appendage closure
left atrial appendage closure

Locations

Country	Name	City	State
France	Hôpital Roger Salengro, CHU	Lille
France	GHICL	Lomme
France	CH De Tourcoing	Tourcoing

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Lille	Institut National de la Santé Et de la Recherche Médicale, France, Ministry of Health, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events	The composite endpoint will enable to evaluate the net clinical benefit of the different therapeutic strategies.; Definition of fatal event: when death is occurring within 30 days after the events.	within 24 months after randomization.
Secondary	Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).	fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).	at 12 and 24 months after randomization
Secondary	Death of any cause	death	at 12 and 24 months after randomization
Secondary	Modified Rankin Scale	functional dependence	at 12 and 24 months after randomization
Secondary	EQ-5D (EuroQoL) Score	health-related quality of life	at 12 and 24 months after randomization
Secondary	neuroradiological biomarkers	on brain MRI	Baseline
Secondary	Complications of endovascular treatment	including device related complications	up to 30 days