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Avoiding Anticoagulation After IntraCerebral Haemorrhage (A3ICH)

Primary Purpose

Intracerebral Hemorrhage, Atrial Fibrillation, Microhaemorrhage

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Apixaban 5 MG
left atrial appendage closure
Sponsored by
University Hospital, Lille
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Intracerebral Hemorrhage focused on measuring intracerebral hemorrhage, atrial fibrillation, microhemorrhage, oral anticoagulation, left atrial appendage closure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hôpital Roger Salengro, CHURecruiting
  • GHICLRecruiting
  • CH De TourcoingRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

No Intervention

Arm Label

Direct Oral Anticoagulant (DOAC)

Left Atrial Appendage Closure (LAAC)

Control

Arm Description

Apixaban 5MG twice daily

Devices will be chosen by local teams.

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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).
Death of any cause
death
Modified Rankin Scale
functional dependence
EQ-5D (EuroQoL) Score
health-related quality of life
neuroradiological biomarkers
on brain MRI
Complications of endovascular treatment
including device related complications

Full Information

First Posted
August 3, 2017
Last Updated
January 26, 2023
Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France, Institut National de la Santé Et de la Recherche Médicale, France
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1. Study Identification

Unique Protocol Identification Number
NCT03243175
Brief Title
Avoiding Anticoagulation After IntraCerebral Haemorrhage
Acronym
A3ICH
Official Title
Avoiding Anticoagulation After IntraCerebral Haemorrhage
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2019 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Lille
Collaborators
Ministry of Health, France, Institut National de la Santé Et de la Recherche Médicale, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage, Atrial Fibrillation, Microhaemorrhage
Keywords
intracerebral hemorrhage, atrial fibrillation, microhemorrhage, oral anticoagulation, left atrial appendage closure

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
1:1:1
Masking
Outcomes Assessor
Masking Description
PROBE design
Allocation
Randomized
Enrollment
300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Direct Oral Anticoagulant (DOAC)
Arm Type
Experimental
Arm Description
Apixaban 5MG twice daily
Arm Title
Left Atrial Appendage Closure (LAAC)
Arm Type
Experimental
Arm Description
Devices will be chosen by local teams.
Arm Title
Control
Arm Type
No Intervention
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Apixaban 5 MG
Other Intervention Name(s)
ELIQUIS 5mg
Intervention Description
Apixaban 5mg x 2 during 24 months
Intervention Type
Device
Intervention Name(s)
left atrial appendage closure
Intervention Description
left atrial appendage closure
Primary Outcome Measure Information:
Title
Composite of all fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events
Description
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.
Time Frame
within 24 months after randomization.
Secondary Outcome Measure Information:
Title
Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
Description
fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).
Time Frame
at 12 and 24 months after randomization
Title
Death of any cause
Description
death
Time Frame
at 12 and 24 months after randomization
Title
Modified Rankin Scale
Description
functional dependence
Time Frame
at 12 and 24 months after randomization
Title
EQ-5D (EuroQoL) Score
Description
health-related quality of life
Time Frame
at 12 and 24 months after randomization
Title
neuroradiological biomarkers
Description
on brain MRI
Time Frame
Baseline
Title
Complications of endovascular treatment
Description
including device related complications
Time Frame
up to 30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Charlotte Cordonnier, MD, PhD
Phone
3 20 44 68 14
Ext
+33
Email
charlotte.cordonnier@chru-lille.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charlotte Cordonnier, MD, PhD
Organizational Affiliation
University Hospital Lille, Inserm, Univ Lille
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Roger Salengro, CHU
City
Lille
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charlottea Cordonnier, MD,PhD
Facility Name
GHICL
City
Lomme
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marta PASQUINI, MD
Facility Name
CH De Tourcoing
City
Tourcoing
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frédéric DUMONT, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
34022170
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. Erratum In: Lancet Neurol. 2021 Jun 9;:
Results Reference
derived

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Avoiding Anticoagulation After IntraCerebral Haemorrhage

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