Avoiding Anticoagulation After IntraCerebral Haemorrhage

Overview

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.

Interventions

• Drug Apixaban 5 MG
  Apixaban 5mg x 2 during 24 months
• Device left atrial appendage closure
  left atrial appendage closure

Primary outcome measures

• Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events [Time frame: within 24 months after randomization.]

Secondary outcome measures (6)

• 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]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

France · 3 centers

• Hôpital Roger Salengro, CHU — Lille
• GHICL — Lomme
• CH De Tourcoing — Tourcoing

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. PMID 36700520
• 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)00 PMID 34022170

Identifiers

NCT: NCT03243175 · 2016_77 · 2017-004371-31

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗