Clinical trial NCT03243175: Avoiding Anticoagulation After IntraCerebral Haemorrhage
Official title: Avoiding Anticoagulation After IntraCerebral Haemorrhage
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Intracerebral Hemorrhage
Atrial Fibrillation
Microhaemorrhage
Keywords: intracerebral hemorrhage
atrial fibrillation
microhemorrhage
oral anticoagulation
left atrial appendage closure
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Institut National de la Santé Et de la Recherche Médicale, France
First posted: 2017-08-08
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1:1
Primary purpose: PREVENTION

Brief 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.

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.

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

Primary outcomes:
measure: Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events
timeFrame: within 24 months after randomization.
Secondary outcomes:
measure: Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
timeFrame: at 12 and 24 months after randomization
measure: Death of any cause
timeFrame: at 12 and 24 months after randomization
measure: Modified Rankin Scale
timeFrame: at 12 and 24 months after randomization
measure: EQ-5D (EuroQoL) Score
timeFrame: at 12 and 24 months after randomization
measure: neuroradiological biomarkers
timeFrame: Baseline
measure: Complications of endovascular treatment
timeFrame: up to 30 days
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro, CHU
city: Lomme
country: France
facility: GHICL
city: Tourcoing
country: France
facility: CH De Tourcoing
Study officials:
affiliation: University Hospital Lille, Inserm, Univ Lille
name: Charlotte Cordonnier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.