Avoiding Anticoagulation After IntraCerebral Haemorrhage (A3ICH)

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.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation; Intracerebral Hemorrhage; Microhaemorrhage
• Intervention / Treatment: Drug: Apixaban 5 MG; Device: left atrial appendage closure

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Charlotte Cordonnier, MD, PhD; Phone Number: +33 3 20 44 68 14; Email: charlotte.cordonnier@chru-lille.fr

Study Locations

• France
  • Lille, France
    • Recruiting
    • Hôpital Roger Salengro, CHU
    • Principal Investigator: Charlottea Cordonnier, MD,PhD
  • Lomme, France
    • Recruiting
    • GHICL
    • Principal Investigator: Marta PASQUINI, MD
  • Tourcoing, France
    • Recruiting
    • CH de Tourcoing
    • Principal Investigator: Frédéric DUMONT, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Direct Oral Anticoagulant (DOAC); Apixaban 5MG twice daily	Drug: Apixaban 5 MG; Apixaban 5mg x 2 during 24 months; Other Names: ELIQUIS 5mg
Experimental: Left Atrial Appendage Closure (LAAC); Devices will be chosen by local teams.	Device: left atrial appendage closure; left atrial appendage closure
No Intervention: Control; avoiding anticoagulation and LAAC during the entire study period The standard clinical practice without OAC may include: antiplatelet drug (in case of comorbidities such as coronary heart disease) or no antithrombotic drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Death of any cause	death	at 12 and 24 months after randomization
Modified Rankin Scale	functional dependence	at 12 and 24 months after randomization
EQ-5D (EuroQoL) Score	health-related quality of life	at 12 and 24 months after randomization
neuroradiological biomarkers	on brain MRI	Baseline
Complications of endovascular treatment	including device related complications	up to 30 days

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; Ministry of Health, France
• Investigators: Principal Investigator: Charlotte Cordonnier, MD, PhD, University Hospital Lille, Inserm, Univ Lille

Publications and helpful links

General Publications

• Cochrane A, Chen C, Stephen J, Ronning OM, Anderson CS, Hankey GJ, Al-Shahi Salman R. Antithrombotic treatment after stroke due to intracerebral haemorrhage. Cochrane Database Syst Rev. 2023 Jan 26;1(1):CD012144. doi: 10.1002/14651858.CD012144.pub3.
• Li L, Poon MTC, Samarasekera NE, Perry LA, Moullaali TJ, Rodrigues MA, Loan JJM, Stephen J, Lerpiniere C, Tuna MA, Gutnikov SA, Kuker W, Silver LE, Al-Shahi Salman R, Rothwell PM. Risks of recurrent stroke and all serious vascular events after spontaneous intracerebral haemorrhage: pooled analyses of two population-based studies. Lancet Neurol. 2021 Jun;20(6):437-447. doi: 10.1016/S1474-4422(21)00075-2.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2019
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: atrial fibrillation; intracerebral hemorrhage; oral anticoagulation; left atrial appendage closure; microhemorrhage
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Hemorrhage; Intracranial Hemorrhages; Pathological Conditions, Signs and Symptoms; Atrial Fibrillation; Cerebral Hemorrhage; Investigative Techniques; Therapeutics; Catheterization; Cardiac Catheterization; apixaban; Left Atrial Appendage Closure
• Other Study ID Numbers: 2016_77; 2017-004371-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Prof Cordonnier (chief investigator of A3ICH) is a member of the international Collaboration Of Controlled Randomised trials of Oral Antithrombotic drugs after intraCranial Haemorrhage (COCROACH - coordination Prof Rustam Al-Shahi Salman, UK) working towards a pre-planned individual patient data meta-analysis
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No