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Apixaban for Treatment of Embolic Stroke of Undetermined Source (ATTICUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02427126
Recruitment Status : Recruiting
First Posted : April 27, 2015
Last Update Posted : December 20, 2018
Information provided by (Responsible Party):
University Hospital Tuebingen

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

Condition or disease Intervention/treatment Phase
Embolic Stroke of Undetermined Source Drug: Apixaban Drug: Aspirin Phase 3

Detailed Description:

Based on the previous data, ATTICUS is designed as multicentre, national, parallel groupactive 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 500 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Apixaban for Treatment of Embolic Stroke of Undetermined Source (ATTICUS Randomized Trial)
Study Start Date : December 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Apixaban
Apixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake
Drug: 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
Other Name: Eliquis

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

Primary Outcome Measures :
  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 [ Time Frame: 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 :
  1. Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism [ Time Frame: 12 months ]
  2. Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death [ Time Frame: 12 months ]
  3. Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria [ Time Frame: 12 months ]
  4. Change of cognitive function (MOCA) [ Time Frame: 12 months ]
  5. Life quality (EQ-5D) [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria Must be ≥ 18 years at the time of signing the informed consent.

  • 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. azoleantimycotics 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02427126

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Contact: Tobias Geisler, Prof 0049 ( 0) 7071 29 87320
Contact: Ulf Ziemann, Prof 0049 ( 0) 7071 29 82049

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MedicalPark Berlin Humboldtmühle GmbH & Co. KG Recruiting
Berlin, Germany
Principal Investigator: Martin Ebinger, PD Dr.         
Klinik für NeurologieKnappschaftskrankenhaus Bochum-Langendreer Withdrawn
Bochum, Germany
Neurologische Klinik, Universität Bonn Recruiting
Bonn, Germany
Contact: Felix Bode, MD         
Regiomed Kliniken Coburg GmbH Abt. II Recruiting
Coburg, Germany
Contact: Johannes Brachmann, Prof         
Neurologie, Klinikum Friedrichshafen GmbH Recruiting
Friedrichshafen, Germany
Contact: Roman Huber, Prof         
Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie, Recruiting
Göttingen, Germany
Contact: Jan Liman, MD         
Krankenhaus Martha-Maria Halle-Döhlau Recruiting
Halle, Germany
Contact: Andrea Kraft, MD         
Klinik für Neurolgie,UKSH Campus Kiel Recruiting
Kiel, Germany
Contact: Johannes Meyne, MD         
Klinik für Neurologie, Klinikum Ludwigsburg Recruiting
Ludwigsburg, Germany
Contact: Martin Schabet, Prof         
Universitätsklinik für Neurologie, Magdeburg Not yet recruiting
Magdeburg, Germany
Contact: Michael Görtler, Prof.         
Carl von Basedow KlinikumSaalekreis gGmbH Recruiting
Merseburg, Germany
Contact: Carsten Hobohm, MD         
Johannes Wesling Kliniken Not yet recruiting
Minden, Germany
Contact: Peter Schellinger, Prof.         
Universitätsklinkum Münster, Stroke Unit Not yet recruiting
Münster, Germany
Contact: Rainer Dziewas, Prof.         
Marienhospital Stuttgart, Klinik für Neurologie Recruiting
Stuttgart, Germany
Contact: Alfred Lindner, Prof         
Neurologische Klinik des Bürgerhospitals Recruiting
Stuttgart, Germany
Contact: Elisabeth Schmid, Dr. med.         
University Hospital Recruiting
Tubingen, Germany, D72076
Contact: Tobias Geisler, Prof         
Contact: Timea Keller, Mrs         
Principal Investigator: Tobias Geisler, Prof.         
Sub-Investigator: Sven Poli, MD         
Sub-Investigator: Jürgen Schreieck, PD Dr.         
Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie Recruiting
Ulm, Germany
Contact: Katharina Althaus, Dr         
Schwarzwald Baar Klinikum GmbH Recruiting
Villingen-Schwenningen, Germany
Contact: Werner Jung, Prof         
Rems-Murr-Klinikum WinnendenNeurologie Recruiting
Winnenden, Germany
Contact: Fabian Hillenbrand, MD         
Sponsors and Collaborators
University Hospital Tuebingen
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Principal Investigator: Tobias Geisler, Prof Tübingen University Hospital

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Responsible Party: University Hospital Tuebingen Identifier: NCT02427126     History of Changes
Other Study ID Numbers: 2014-005109-19
First Posted: April 27, 2015    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: May 2018

Keywords provided by University Hospital Tuebingen:

Additional relevant MeSH terms:
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Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Salicylic Acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Factor Xa Inhibitors
Serine Proteinase Inhibitors
Protease Inhibitors