Apixaban for Treatment of Embolic Stroke of Undetermined Source

NCT ID: NCT02427126

Last Updated: 2021-10-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 352 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-09-30

Brief Summary

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

Detailed Description

Based on the previous data, ATTICUS is designed as multicentre, national, parallel group, active controlled, phase III randomized (2x2 factorial), clinical trial to demonstrate the superiority of apixaban against the current standard of treatment (acetylsalicylic acid) for the longterm treatment after ESUS. ATTICUS will follow a dynamic treatment protocol implementing conversion from the acetylsalicylic acid arm to the apixaban arm in case of detection of relevant episodes of AF during the course of the study. ATTICUS is designed to test the superiority over acetylsalicylic acid to reduce new ischemic lesion detected by FLAIR/DWI MRI.

Conditions

Embolic Stroke of Undetermined Source

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Apixaban

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

Group Type: EXPERIMENTAL

Apixaban

Intervention Type: 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

Aspirin

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

Group Type: ACTIVE_COMPARATOR

Aspirin

Intervention Type: DRUG

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

Interventions

Apixaban

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

Intervention Type: DRUG

Aspirin

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

Intervention Type: DRUG

Other Intervention Names

Eliquis

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• Severe renal failure, defined as Glomerular Filtration Rate (GFR) <15ml/min
• Severe hepatic insufficiency (Child-Pugh score B to C),
• Active liver disease,
• Contraindications against performance of MRI (pacemaker/ICD), previous implantation non-MRI capable protheses
• Patients considered unreliable by the investigator, or having a life expectancy less than the expected duration of the trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Medtronic

INDUSTRY

Sponsor Role: collaborator

ZKS and IKEaB Tübingen

UNKNOWN

Sponsor Role: collaborator

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tobias Geisler, Prof

Role: PRINCIPAL_INVESTIGATOR

Tübingen University Hospital

Sven Poli, Prof

Role: PRINCIPAL_INVESTIGATOR

Tübingen University Hospital

Schreieck Jürgen, Prof

Role: PRINCIPAL_INVESTIGATOR

Tübingen University Hospital

Locations

MedicalPark Berlin Humboldtmühle GmbH & Co. KG

Berlin, , Germany

Neurologische Klinik, Universität Bonn

Bonn, , Germany

Regiomed Kliniken Coburg GmbH Abt. II

Coburg, , Germany

Neurologie, Klinikum Friedrichshafen GmbH

Friedrichshafen, , Germany

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

Göttingen, , Germany

Krankenhaus Martha-Maria Halle-Döhlau

Halle, , Germany

Klinik für Neurolgie,UKSH Campus Kiel

Kiel, , Germany

Klinik für Neurologie, Klinikum Ludwigsburg

Ludwigsburg, , Germany

Universitätsklinik für Neurologie, Magdeburg

Magdeburg, , Germany

Carl von Basedow KlinikumSaalekreis gGmbH

Merseburg, , Germany

Marienhospital Stuttgart, Klinik für Neurologie

Stuttgart, , Germany

Neurologische Klinik des Bürgerhospitals

Stuttgart, , Germany

University Hospital

Tübingen, , Germany

Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie

Ulm, , Germany

Schwarzwald Baar Klinikum GmbH

Villingen-Schwenningen, , Germany

Rems-Murr-Klinikum WinnendenNeurologie

Winnenden, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 38320511 (View on PubMed)

Other Identifiers

2014-005109-19

Identifier Type: -

Identifier Source: org_study_id