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Avoiding Anticoagulation After IntraCerebral Haemorrhage (A3ICH)

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ClinicalTrials.gov Identifier: NCT03243175
Recruitment Status : Recruiting
First Posted : August 8, 2017
Last Update Posted : February 18, 2019
Sponsor:
Collaborators:
Ministry of Health, France
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
University Hospital, Lille

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.


Condition or disease Intervention/treatment Phase
Intracerebral Hemorrhage Atrial Fibrillation Microhaemorrhage Drug: Apixaban 5 MG Device: left atrial appendage closure Phase 3

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.


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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 2023
Estimated Study Completion Date : December 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding
Drug Information available for: Apixaban

Arm Intervention/treatment
Experimental: Direct Oral Anticoagulant (DOAC)
Apixaban 5MG twice daily
Drug: Apixaban 5 MG
Apixaban 5mg x 2 during 24 months
Other Name: 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



Primary Outcome Measures :
  1. 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.



Secondary Outcome Measures :
  1. 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).

  2. Death of any cause [ Time Frame: at 12 and 24 months after randomization ]
    death

  3. Modified Rankin Scale [ Time Frame: at 12 and 24 months after randomization ]
    functional dependence

  4. EQ-5D (EuroQoL) Score [ Time Frame: at 12 and 24 months after randomization ]
    health-related quality of life

  5. neuroradiological biomarkers [ Time Frame: Baseline ]
    on brain MRI

  6. 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
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
  • 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

Information from the National Library of Medicine

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


Contacts
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Contact: Charlotte Cordonnier, MD, PhD 3 20 44 68 14 ext +33 charlotte.cordonnier@chru-lille.fr

Locations
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France
Hôpital Roger Salengro, CHU Recruiting
Lille, France
Principal Investigator: Charlottea Cordonnier, MD,PhD         
Sponsors and Collaborators
University Hospital, Lille
Ministry of Health, France
Institut National de la Santé Et de la Recherche Médicale, France
Investigators
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Principal Investigator: Charlotte Cordonnier, MD, PhD University Hospital Lille, Inserm, Univ Lille

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Responsible Party: University Hospital, Lille
ClinicalTrials.gov Identifier: NCT03243175     History of Changes
Other Study ID Numbers: 2016_77
2017-004371-31 ( EudraCT Number )
First Posted: August 8, 2017    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019
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)

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Lille:
intracerebral hemorrhage
atrial fibrillation
microhemorrhage
oral anticoagulation
left atrial appendage closure

Additional relevant MeSH terms:
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Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Atrial Fibrillation
Hemorrhage
Cerebral 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
Antithrombins
Molecular Mechanisms of Pharmacological Action
Anticoagulants