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

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ClinicalTrials.gov Identifier: NCT02427126
Recruitment Status : Recruiting
First Posted : April 27, 2015
Last Update Posted : December 20, 2018
Sponsor:
Information provided by (Responsible Party):
University Hospital Tuebingen

Tracking Information
First Submitted Date  ICMJE March 20, 2015
First Posted Date  ICMJE April 27, 2015
Last Update Posted Date December 20, 2018
Study Start Date  ICMJE December 2015
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: April 24, 2015)
Occurrence of at least one new ischemic lesion identified by magnetic resonance imaging at 12 months when compared to the baseline MRI (FLAIR, DWI) obtained at the time of study drug initiation. [ Time Frame: 12 months ]
Change History Complete list of historical versions of study NCT02427126 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism [ Time Frame: 12 months ]
  • Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death [ Time Frame: 12 months ]
  • Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria [ Time Frame: 12 months ]
  • Change of cognitive function (MOCA) [ Time Frame: 12 months ]
  • Life quality (EQ-5D) [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban for Treatment of Embolic Stroke of Undetermined Source
Official Title  ICMJE Apixaban for Treatment of Embolic Stroke of Undetermined Source (ATTICUS Randomized Trial)
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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Embolic Stroke of Undetermined Source
Intervention  ICMJE
  • 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
  • Drug: Aspirin
    Acetylic Salicylic Acid 100mg o.d.; 12 Months
Study Arms  ICMJE
  • Experimental: Apixaban
    Apixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake
    Intervention: Drug: Apixaban
  • Active Comparator: Aspirin
    Acetylic Salicylic Acid 100mg o.d.; Study treatment: 12 months Follow-up: 30 days after last study drug intake
    Intervention: Drug: Aspirin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 24, 2015)
500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2021
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Tobias Geisler, Prof 0049 ( 0) 7071 29 87320 tobias.geisler@med.uni-tuebingen.de
Contact: Ulf Ziemann, Prof 0049 ( 0) 7071 29 82049 Ulf.Ziemann@med.uni-tuebingen.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02427126
Other Study ID Numbers  ICMJE 2014-005109-19
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital Tuebingen
Study Sponsor  ICMJE University Hospital Tuebingen
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tobias Geisler, Prof Tübingen University Hospital
PRS Account University Hospital Tuebingen
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP