Apixaban for Treatment of Embolic Stroke of Undetermined Source
- Conditions
- Embolic Stroke of Undetermined Source
- Interventions
- Registration Number
- NCT02427126
- Lead Sponsor
- University Hospital Tuebingen
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 352
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Aspirin Aspirin Acetylic Salicylic Acid 100mg o.d.; Study treatment: 12 months Follow-up: 30 days after last study drug intake Apixaban Apixaban Apixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake
- Primary Outcome Measures
Name Time Method 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 12 months 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.
- Secondary Outcome Measures
Name Time Method Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism 12 months The occurence of ischaemic stroke, hemorrhagic stroke, or systemic embolism during study participation (12months) will be quantified
Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death 12 months The occurence of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death during study participation (12months) will be quantified
Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria 12 months The occurence of major and clinically relevant non-major bleedings defined according to ISTH criteria during study participation (12months) will be quantified
Change of cognitive function (MOCA) 12 months MOCA test will be performed upon study enrollment and 12 months after enrollment and both tests will be compared
Life quality (EQ-5D) 12 months EQ-5D questionnaire will be raised upon study enrollment and 12 months after enrollment and both questionnaires will be compared
Trial Locations
- Locations (16)
Regiomed Kliniken Coburg GmbH Abt. II
🇩🇪Coburg, Germany
Neurologie, Klinikum Friedrichshafen GmbH
🇩🇪Friedrichshafen, Germany
Carl von Basedow KlinikumSaalekreis gGmbH
🇩🇪Merseburg, Germany
Klinik für Neurolgie,UKSH Campus Kiel
🇩🇪Kiel, Germany
Klinik für Neurologie, Klinikum Ludwigsburg
🇩🇪Ludwigsburg, Germany
Neurologische Klinik des Bürgerhospitals
🇩🇪Stuttgart, Germany
Marienhospital Stuttgart, Klinik für Neurologie
🇩🇪Stuttgart, Germany
University Hospital
🇩🇪Tubingen, Germany
Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie
🇩🇪Ulm, Germany
Schwarzwald Baar Klinikum GmbH
🇩🇪Villingen-Schwenningen, Germany
Neurologische Klinik, Universität Bonn
🇩🇪Bonn, Germany
MedicalPark Berlin Humboldtmühle GmbH & Co. KG
🇩🇪Berlin, Germany
Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie,
🇩🇪Göttingen, Germany
Krankenhaus Martha-Maria Halle-Döhlau
🇩🇪Halle, Germany
Universitätsklinik für Neurologie, Magdeburg
🇩🇪Magdeburg, Germany
Rems-Murr-Klinikum WinnendenNeurologie
🇩🇪Winnenden, Germany