Avoiding Anticoagulation After IntraCerebral Haemorrhage (A3ICH)
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| ClinicalTrials.gov Identifier: NCT03243175 |
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Recruitment Status :
Recruiting
First Posted : August 8, 2017
Last Update Posted : January 27, 2023
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Intracerebral Hemorrhage Atrial Fibrillation Microhaemorrhage | Drug: Apixaban 5 MG Device: left atrial appendage closure | Phase 3 |
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 (Clinical Trial) |
| Estimated Enrollment : | 300 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | 1:1:1 |
| Masking: | Single (Outcomes Assessor) |
| Masking Description: | PROBE design |
| Primary Purpose: | Prevention |
| Official Title: | Avoiding Anticoagulation After IntraCerebral Haemorrhage |
| Actual Study Start Date : | January 24, 2019 |
| Estimated Primary Completion Date : | December 2026 |
| Estimated Study Completion Date : | December 2026 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Direct Oral Anticoagulant (DOAC)
Apixaban 5MG twice daily
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Drug: Apixaban 5 MG
Apixaban 5mg x 2 during 24 months
Other Name: ELIQUIS 5mg |
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Experimental: Left Atrial Appendage Closure (LAAC)
Devices will be chosen by local teams.
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Device: left atrial appendage closure
left atrial appendage closure |
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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
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- 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.
- 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 ]fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
- Death of any cause [ Time Frame: at 12 and 24 months after randomization ]death
- Modified Rankin Scale [ Time Frame: at 12 and 24 months after randomization ]functional dependence
- EQ-5D (EuroQoL) Score [ Time Frame: at 12 and 24 months after randomization ]health-related quality of life
- neuroradiological biomarkers [ Time Frame: Baseline ]on brain MRI
- Complications of endovascular treatment [ Time Frame: up to 30 days ]including device related complications
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03243175
| Contact: Charlotte Cordonnier, MD, PhD | 3 20 44 68 14 ext +33 | charlotte.cordonnier@chru-lille.fr |
| France | |
| Hôpital Roger Salengro, CHU | Recruiting |
| Lille, France | |
| Principal Investigator: Charlottea Cordonnier, MD,PhD | |
| GHICL | Recruiting |
| Lomme, France | |
| Principal Investigator: Marta PASQUINI, MD | |
| CH De Tourcoing | Recruiting |
| Tourcoing, France | |
| Principal Investigator: Frédéric DUMONT, MD | |
| Principal Investigator: | Charlotte Cordonnier, MD, PhD | University Hospital Lille, Inserm, Univ Lille |
| Responsible Party: | University Hospital, Lille |
| ClinicalTrials.gov Identifier: | NCT03243175 |
| Other Study ID Numbers: |
2016_77 2017-004371-31 ( EudraCT Number ) |
| First Posted: | August 8, 2017 Key Record Dates |
| Last Update Posted: | January 27, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| 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 |
| Supporting Materials: |
Study Protocol Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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intracerebral hemorrhage atrial fibrillation microhemorrhage oral anticoagulation left atrial appendage closure |
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Cerebral Hemorrhage Atrial Fibrillation Hemorrhage Arrhythmias, Cardiac Heart Diseases Cardiovascular Diseases Pathologic Processes Intracranial Hemorrhages Cerebrovascular Disorders Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Vascular Diseases Apixaban Factor Xa Inhibitors Antithrombins Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants |