Apixaban for Treatment of Embolic Stroke of Undetermined Source

NCT02427126 | Completed Phase 3

• 1 other identifier: 2014-005109-19
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 16

Brief Summary

Multicentre (national, Germany), randomized (2x2 factorial), open, parallel group, active controlled, efficacy study (phase III)

Conditions

Embolic Stroke of Undetermined Source

Keywords

ESUS; anticoagulation

Outcome Measures

Primary Outcomes (1)

• Imaging Endpoint: Occurrence of at least one new ischemic lesion at 12 months after study drug initiation when compared to baseline MRI before study drug initiation

  The primary endpoint will be the occurrence of at least one new ischemic lesion identified by magnetic resonance imaging (axial T2-weighted fluid attenuated inversion recovery MRI (FLAIR) and/or axial diffusion weighted MRI (DWI)) at 12 months when compared to the baseline MRI (FLAIR, DWI) obtained at the time of study drug initiation. MRI at 12 months will be directly compared with the baseline MRI to assess for new ischemic lesions.

  12 months

Secondary Outcomes (5)

• Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism

  12 months

• Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death

  12 months

• Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria

  12 months

• Change of cognitive function (MOCA)

  12 months

• Life quality (EQ-5D)

  12 months

Study Arms (2)

Apixaban

EXPERIMENTAL

Apixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake

Drug: Apixaban

Aspirin

ACTIVE COMPARATOR

Acetylic Salicylic Acid 100mg o.d.; Study treatment: 12 months Follow-up: 30 days after last study drug intake

Drug: Aspirin

Interventions

Apixaban DRUG

Apixaban is an oral anticoagulant currently approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, for the treatment of deep vein thrombosis and pulmonary embolism, and for the prophylaxis of systemic embolism after orthopedic surgery

Also known as: Eliquis

Apixaban

Aspirin DRUG

Acetylic Salicylic Acid 100mg o.d.; 12 Months

Aspirin

Eligibility Criteria

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

You may qualify if:

• ESUS must be defined according to following criteria:
• Stroke detected by CT or MRI that is not lacunar
• Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischaemia
• No major-risk cardioembolic source of embolism
• No other specific cause of stroke identified
• \* At least one of the following non-major but suggestive risk factors for cardiac embolism:
• LA size \>45mm (parasternal axis)
• spontaneous echo contrast in LAA
• LAA flow velocity \<=0.2m/s
• atrial high rate episodes
• CHA2DS2-Vasc score \>=4
• persistent foramen ovale
• Understand and voluntarily sign an informed consent document
• Women of childbearing potential (WOCBP) must be using an adequate method of contraception.

You may not qualify if:

• History of hypersensitivity to the investigational medicinal product
• Participation in other clinical trials or observation period of competing trials.
• Arteria cerebri media stroke affecting \> 30% of c o r r e s p o n d i n g territory
• Diagnosis of haemorrhage or other pathology,
• Clear indication for anticoagulation
• Inability to control following risk factors for Hemorrhagic Transformation of fresh cerebral Infarction (HTI) during index hospital stay: presence of HTI at the time of anticoagulation, blood pressure \>140 mmHg systolic, abnormal blood glucose Clear indication for dual antiplatelet therapy
• Clear stroke-/non-stroke-indication for concomitant long-term therapy with antiplatelets (e.g. acetylsalicylic acid (ASA), Clopidogrel, or Prasugrel) or with non-steroidal anti-inflammatory drugs (NSAID).
• Concomitant systemic therapy with strong inhibitors of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. azole antimycotics and human immunodeficiency virus (HIV)-protease inhibitors.
• Contraindication to investigational medications
• Planned or likely therapy with fibrinolytic agents within 48 hours of first study medication
• History of intracranial, intraocular, spinal, retroperitoneal or atraumatic intra-articular bleeding
• Gastrointestinal bleed or major surgery within 3 months
• Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months
• TIA or minor stroke induced by angiography or surgery
• Severe non-cardiovascular comorbidity with life expectancy \< 3 months

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• Bristol-Myers Squibb: collaborator
• Medtronic: collaborator
• ZKS and IKEaB Tübingen: collaborator

Study Sites (16)

MedicalPark Berlin Humboldtmühle GmbH & Co. KG

Berlin, Germany

Location

Neurologische Klinik, Universität Bonn

Bonn, Germany

Location

Regiomed Kliniken Coburg GmbH Abt. II

Coburg, Germany

Location

Neurologie, Klinikum Friedrichshafen GmbH

Friedrichshafen, Germany

Location

Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie,

Göttingen, Germany

Location

Krankenhaus Martha-Maria Halle-Döhlau

Halle, Germany

Location

Klinik für Neurolgie,UKSH Campus Kiel

Kiel, Germany

Location

Klinik für Neurologie, Klinikum Ludwigsburg

Ludwigsburg, Germany

Location

Universitätsklinik für Neurologie, Magdeburg

Magdeburg, Germany

Location

Carl von Basedow KlinikumSaalekreis gGmbH

Merseburg, Germany

Location

Marienhospital Stuttgart, Klinik für Neurologie

Stuttgart, Germany

Location

Neurologische Klinik des Bürgerhospitals

Stuttgart, Germany

Location

University Hospital

Tübingen, D72076, Germany

Location

Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie

Ulm, Germany

Location

Schwarzwald Baar Klinikum GmbH

Villingen-Schwenningen, Germany

Location

Rems-Murr-Klinikum WinnendenNeurologie

Winnenden, Germany

Location

Related Publications (1)

• Geisler T, Keller T, Martus P, Poli K, Serna-Higuita LM, Schreieck J, Gawaz M, Tunnerhoff J, Bombach P, Nagele T, Klose U, Aidery P, Groga-Bada P, Kraft A, Hoffmann F, Hobohm C, Naupold K, Niehaus L, Wolf M, Bazner H, Liman J, Wachter R, Kimmig H, Jung W, Huber R, Feurer R, Lindner A, Althaus K, Bode FJ, Petzold GC, Nguyen TN, Mac Grory B, Schrag M, Purrucker JC, Zuern CS, Ziemann U, Poli S; ATTICUS Investigators. Apixaban versus Aspirin for Embolic Stroke of Undetermined Source. NEJM Evid. 2024 Jan;3(1):EVIDoa2300235. doi: 10.1056/EVIDoa2300235. Epub 2023 Dec 22.

  PMID: 38320511 DERIVED

MeSH Terms

Interventions

apixaban; Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Tobias Geisler, Prof

  Tübingen University Hospital

  PRINCIPAL INVESTIGATOR

• Sven Poli, Prof

  Tübingen University Hospital

  PRINCIPAL INVESTIGATOR

• Schreieck Jürgen, Prof

  Tübingen University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 20, 2015
• First Posted: April 27, 2015
• Study Start: December 1, 2015
• Primary Completion: August 1, 2020
• Study Completion: September 1, 2021
• Last Updated: October 13, 2021

Record last verified: 2021-09

Locations

DE (16)