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

October 12, 2021 updated by: University Hospital Tuebingen

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

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
352

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany
        • MedicalPark Berlin Humboldtmühle GmbH & Co. KG
      • Bonn, Germany
        • Neurologische Klinik, Universität Bonn
      • Coburg, Germany
        • Regiomed Kliniken Coburg GmbH Abt. II
      • Friedrichshafen, Germany
        • Neurologie, Klinikum Friedrichshafen GmbH
      • Göttingen, Germany
        • Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie,
      • Halle, Germany
        • Krankenhaus Martha-Maria Halle-Döhlau
      • Kiel, Germany
        • Klinik für Neurolgie,UKSH Campus Kiel
      • Ludwigsburg, Germany
        • Klinik für Neurologie, Klinikum Ludwigsburg
      • Magdeburg, Germany
        • Universitätsklinik für Neurologie, Magdeburg
      • Merseburg, Germany
        • Carl von Basedow KlinikumSaalekreis gGmbH
      • Stuttgart, Germany
        • Marienhospital Stuttgart, Klinik für Neurologie
      • Stuttgart, Germany
        • Neurologische Klinik des Bürgerhospitals
      • Tubingen, Germany, D72076
        • University Hospital
      • Ulm, Germany
        • Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie
      • Villingen-Schwenningen, Germany
        • Schwarzwald Baar Klinikum GmbH
      • Winnenden, Germany
        • Rems-Murr-Klinikum WinnendenNeurologie

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism
Time Frame: 12 months
The occurence of ischaemic stroke, hemorrhagic stroke, or systemic embolism during study participation (12months) will be quantified
12 months
Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death
Time Frame: 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
12 months
Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria
Time Frame: 12 months
The occurence of major and clinically relevant non-major bleedings defined according to ISTH criteria during study participation (12months) will be quantified
12 months
Change of cognitive function (MOCA)
Time Frame: 12 months
MOCA test will be performed upon study enrollment and 12 months after enrollment and both tests will be compared
12 months
Life quality (EQ-5D)
Time Frame: 12 months
EQ-5D questionnaire will be raised upon study enrollment and 12 months after enrollment and both questionnaires will be compared
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Hospital Tuebingen

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bristol-Myers Squibb
Medtronic
ZKS and IKEaB Tübingen

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tobias Geisler, Prof, Tubingen University Hospital
  • Principal Investigator: Sven Poli, Prof, Tubingen University Hospital
  • Principal Investigator: Schreieck Jürgen, Prof, Tubingen University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 20, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 27, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 13, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 12, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-005109-19

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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