Avoiding Anticoagulation After IntraCerebral Haemorrhage

NCT03243175 | Recruiting Phase 3 DMC

• 2 other identifiers: 2016_772017-004371-31
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 3

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.

Conditions

Intracerebral Hemorrhage; Atrial Fibrillation; Microhaemorrhage

Keywords

intracerebral hemorrhage; atrial fibrillation; microhemorrhage; oral anticoagulation; left atrial appendage closure

Outcome Measures

Primary Outcomes (1)

• 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.

  within 24 months after randomization.

Secondary Outcomes (6)

• Each individual component of the composite outcome (fatal or non-fatal major cardiovascular/cerebrovascular ischaemic or haemorrhagic intracranial/extracranial events).

  at 12 and 24 months after randomization

• Death of any cause

  at 12 and 24 months after randomization

• Modified Rankin Scale

  at 12 and 24 months after randomization

• EQ-5D (EuroQoL) Score

  at 12 and 24 months after randomization

• neuroradiological biomarkers

  Baseline

Study Arms (3)

Direct Oral Anticoagulant (DOAC)

EXPERIMENTAL

Apixaban 5MG twice daily

Drug: Apixaban 5 MG

Left Atrial Appendage Closure (LAAC)

EXPERIMENTAL

Devices will be chosen by local teams.

Device: left atrial appendage closure

Control

NO INTERVENTION

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

Interventions

Apixaban 5 MG DRUG

Apixaban 5mg x 2 during 24 months

Also known as: ELIQUIS 5mg

Direct Oral Anticoagulant (DOAC)

left atrial appendage closure DEVICE

left atrial appendage closure

Left Atrial Appendage Closure (LAAC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• University Hospital, Lille: lead
• Ministry of Health, France: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (3)

Hôpital Roger Salengro, CHU

Lille, France

RECRUITING

GHICL

Lomme, France

RECRUITING

CH De Tourcoing

Tourcoing, France

RECRUITING

Related Publications (2)

• 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 DERIVED

• 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.

  PMID: 34022170 DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage; Atrial Fibrillation

Interventions

apixaban; Left Atrial Appendage Closure

Condition Hierarchy (Ancestors)

Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases

Intervention Hierarchy (Ancestors)

Cardiac Catheterization; Catheterization; Therapeutics; Investigative Techniques

Study Officials

• Charlotte Cordonnier, MD, PhD

  University Hospital Lille, Inserm, Univ Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Charlotte Cordonnier, MD, PhD

CONTACT

3 20 44 68 14; charlotte.cordonnier@chru-lille.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: PROBE design
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1:1

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 8, 2017
• Study Start: January 17, 2019
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 6, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR

Locations

FR (3)