Intracerebral HemorrhagePhase 3A3ICHNCT03243175
Avoiding Anticoagulation After IntraCerebral Haemorrhage
A Phase 3 study testing Apixaban 5 MG and left atrial appendage closure in people with Intracerebral Hemorrhage and Atrial Fibrillation, run by University Hospital, Lille at 3 sites in France.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Intracerebral Hemorrhage, Atrial Fibrillation, Microhaemorrhage
- What is being tested?
- Apixaban 5 MG and left atrial appendage closure
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 3 sitesFrance
- Study dates
- 17 Jan 2019to Dec 2029
- Phase
- Phase 3
- 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
- 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.
Who cannot join
- 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
- Contraindications due to local, anatomical reasons (such as thrombus in the left atrial appendage, infection with a risk of endocarditis)
Show all 14Show fewer
- Patients older than 85 years
- CHA2DS2VASc score of 2 or 3
- Patient or attending physician are unwilling to undergo/perform intervention for LAAC
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
France3 sites, 3 recruiting
- Recruiting
Hôpital Roger Salengro, CHU
Lille
Charlottea Cordonnier, MD,PhD
- Recruiting
GHICL
Lomme
Marta PASQUINI, MD
- Recruiting
CH De Tourcoing
Tourcoing
Frédéric DUMONT, MD
About this study
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.
Read the 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.
- Being tested
- Apixaban 5 MG, left atrial appendage closure
- Keywords
- intracerebral hemorrhage, atrial fibrillation, microhemorrhage, oral anticoagulation, left atrial appendage closure
- Medical subject headings
- Cerebral Hemorrhage, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Apixaban 5 MGDrug
Also called ELIQUIS 5mg
Apixaban 5mg x 2 during 24 months
left atrial appendage closureDevice
left atrial appendage closure
| Study group | Role | What they receive |
|---|---|---|
| Direct Oral Anticoagulant (DOAC) | Experimental | Apixaban 5MG twice daily Receives: Drug: Apixaban 5 MG |
| Left Atrial Appendage Closure (LAAC) | Experimental | Devices will be chosen by local teams. Receives: Device: left atrial appendage closure |
| Control | No intervention | 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: within 24 months after randomization.
Secondary outcomes (6)
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).
Measured: at 12 and 24 months after randomization
Death of any cause
death
Measured: at 12 and 24 months after randomization
Modified Rankin Scale
functional dependence
Measured: at 12 and 24 months after randomization
EQ-5D (EuroQoL) Score
health-related quality of life
Measured: at 12 and 24 months after randomization
neuroradiological biomarkers
on brain MRI
Measured: Baseline
Complications of endovascular treatment
including device related complications
Measured: up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2017
- Study start17 Jan 2019
- Primary completionJan 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Intracerebral HemorrhageStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1:1
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France, Institut National de la Santé Et de la Recherche Médicale, France
- Responsible party
- Sponsor
- Investigators
- Charlotte Cordonnier, MD, PhD, Principal investigator, University Hospital Lille, Inserm, Univ Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03243175
- Sponsor's protocol ID
- 2016_77
- Other IDs
- 2017-004371-31, 2017
- Acronym
- A3ICH
- Status last verified
- Apr 2026
- First submitted
- 3 Aug 2017
- Last updated
- 7 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
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.
PubMed 36700520Li 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.
PubMed 34022170
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Avoiding Anticoagulation After IntraCerebral Haemorrhage
- ClinicalTrials.gov ID
- NCT03243175
- Acronym / sponsor ID
- A3ICH / 2016_77
- Keywords
- intracerebral hemorrhage, atrial fibrillation, microhemorrhage, oral anticoagulation, left atrial appendage closure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Collaborators
- Ministry of Health, France, Institut National de la Santé Et de la Recherche Médicale, France
- Study start
- 17 Jan 2019 (actual)
- Primary completion
- Jan 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 8 Aug 2017 (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.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- 1:1:1
| Arm | Type | Receives |
|---|---|---|
| Direct Oral Anticoagulant (DOAC) | Experimental | Drug: Apixaban 5 MGApixaban 5MG twice daily |
| Left Atrial Appendage Closure (LAAC) | Experimental | Device: left atrial appendage closureDevices will be chosen by local teams. |
| Control | No intervention | –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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| Apixaban 5 MGAlso: ELIQUIS 5mgApixaban 5mg x 2 during 24 months | Drug | Direct Oral Anticoagulant (DOAC) |
| left atrial appendage closureleft atrial appendage closure | Device | Left Atrial Appendage Closure (LAAC) |
Primary outcome
Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events
Time frame: within 24 months after randomization.
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.
6 secondary outcomes
Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
Time frame: at 12 and 24 months after randomization
Death of any cause
Time frame: at 12 and 24 months after randomization
Modified Rankin Scale
Time frame: at 12 and 24 months after randomization
EQ-5D (EuroQoL) Score
Time frame: at 12 and 24 months after randomization
neuroradiological biomarkers
Time frame: Baseline
Complications of endovascular treatment
Time frame: up to 30 days
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 7 Apr 2026.
- Derived from this study: PubMed 36700520Cochrane 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.
- Derived from this study: PubMed 34022170Li 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.
- Individual participant dataSharing planned: Yes. 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
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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.
Charlotte Cordonnier, MD, PhD principal investigator
University Hospital Lille, Inserm, Univ Lille
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban 5 MG and left atrial appendage closure in people with Intracerebral Hemorrhage and Atrial Fibrillation, run by University Hospital, Lille at 3 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 6 inclusion and 14 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 7 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Charlotte Cordonnier, MD, PhD (3 20 44 68 14 ext. +33, charlotte.cordonnier@chru-lille.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events (time frame: within 24 months after randomization.). 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 NCT03243175, which also lists 2 linked publications.
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 7 Apr 2026.