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ATTICUS: Apixaban for Treatment of Embolic Stroke of Undetermined Source

Sponsor
University Hospital Tuebingen (Other)
Overall Status
Completed
CT.gov ID
NCT02427126
Collaborator
Bristol-Myers Squibb (Industry), Medtronic (Industry), ZKS and IKEaB Tübingen (Other)
352
Enrollment
16
Locations
2
Arms
69
Actual Duration (Months)
22
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
352 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Apixaban for Treatment of Embolic Stroke of Undetermined Source (ATTICUS Randomized Trial)
Actual Study Start Date :
Dec 1, 2015
Actual Primary Completion Date :
Aug 1, 2020
Actual Study Completion Date :
Sep 1, 2021

Arms and Interventions

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 Names:
  • 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

    Outcome Measures

    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 [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 [12 months]

      The occurence of ischaemic stroke, hemorrhagic stroke, or systemic embolism during study participation (12months) will be quantified

    2. 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

    3. 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

    4. 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

    5. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    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. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 MedicalPark Berlin Humboldtmühle GmbH & Co. KG Berlin Germany
    2 Neurologische Klinik, Universität Bonn Bonn Germany
    3 Regiomed Kliniken Coburg GmbH Abt. II Coburg Germany
    4 Neurologie, Klinikum Friedrichshafen GmbH Friedrichshafen Germany
    5 Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie, Göttingen Germany
    6 Krankenhaus Martha-Maria Halle-Döhlau Halle Germany
    7 Klinik für Neurolgie,UKSH Campus Kiel Kiel Germany
    8 Klinik für Neurologie, Klinikum Ludwigsburg Ludwigsburg Germany
    9 Universitätsklinik für Neurologie, Magdeburg Magdeburg Germany
    10 Carl von Basedow KlinikumSaalekreis gGmbH Merseburg Germany
    11 Marienhospital Stuttgart, Klinik für Neurologie Stuttgart Germany
    12 Neurologische Klinik des Bürgerhospitals Stuttgart Germany
    13 University Hospital Tubingen Germany D72076
    14 Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie Ulm Germany
    15 Schwarzwald Baar Klinikum GmbH Villingen-Schwenningen Germany
    16 Rems-Murr-Klinikum WinnendenNeurologie Winnenden Germany

    Sponsors and Collaborators

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

    Investigators

    • Principal Investigator: Tobias Geisler, Prof, Tübingen University Hospital
    • Principal Investigator: Sven Poli, Prof, Tübingen University Hospital
    • Principal Investigator: Schreieck Jürgen, Prof, Tübingen University Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University Hospital Tuebingen
    ClinicalTrials.gov Identifier:
    NCT02427126
    Other Study ID Numbers:
    • 2014-005109-19
    First Posted:
    Apr 27, 2015
    Last Update Posted:
    Oct 13, 2021
    Last Verified:
    Sep 1, 2021
    Keywords provided by University Hospital Tuebingen
    ESUS
    anticoagulation
    Additional relevant MeSH terms:
    Stroke
    Embolic Stroke
    Aspirin
    Apixaban

    Study Results

    No Results Posted as of Oct 13, 2021