Embolic Stroke of Undetermined SourcePhase 3ATTICUSNCT02427126
Apixaban for Treatment of Embolic Stroke of Undetermined Source
A Phase 3 study testing Apixaban and Aspirin in people with Embolic Stroke of Undetermined Source, run by University Hospital Tuebingen at 16 sites in Germany.
Trial summary
Multicentre (national, Germany), randomized (2x2 factorial), open, parallel group, active controlled, efficacy study (phase III) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Embolic Stroke of Undetermined Source
- What is being tested?
- Apixaban and Aspirin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 352 participants
- Where
- 16 sitesGermany
- Study dates
- Dec 2015to Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
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- 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
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Germany16 sites
MedicalPark Berlin Humboldtmühle GmbH & Co. KG
Berlin
Neurologische Klinik, Universität Bonn
Bonn
Regiomed Kliniken Coburg GmbH Abt. II
Coburg
Neurologie, Klinikum Friedrichshafen GmbH
Friedrichshafen
Universitätsmedizin Göttingen Abt.Innere Medizin, Klinik für Kardiologie und Pneumologie,
Göttingen
Krankenhaus Martha-Maria Halle-Döhlau
Halle
Klinik für Neurolgie,UKSH Campus Kiel
Kiel
Klinik für Neurologie, Klinikum Ludwigsburg
Ludwigsburg
Universitätsklinik für Neurologie, Magdeburg
Magdeburg
Carl von Basedow KlinikumSaalekreis gGmbH
Merseburg
Marienhospital Stuttgart, Klinik für Neurologie
Stuttgart
Neurologische Klinik des Bürgerhospitals
Stuttgart
University Hospital
Tübingen, D72076
Universitäts- und Rehabilitationskliniken Ulm,Klinik für Neurologie
Ulm
Schwarzwald Baar Klinikum GmbH
Villingen-Schwenningen
Rems-Murr-Klinikum WinnendenNeurologie
Winnenden
About this study
Official title: 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)
Read the 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.
- Conditions
- Embolic Stroke of Undetermined Source
- Keywords
- ESUS, anticoagulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApixabanDrug
Also called Eliquis
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
AspirinDrug
Acetylic Salicylic Acid 100mg o.d.; 12 Months
| Study group | Role | What they receive |
|---|---|---|
| Apixaban | Experimental | Apixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake Receives: Drug: Apixaban |
| Aspirin | Active comparator | Acetylic Salicylic Acid 100mg o.d.; Study treatment: 12 months Follow-up: 30 days after last study drug intake Receives: Drug: Aspirin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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.
Measured: 12 months
Secondary outcomes (5)
Combination of recurrent ischaemic stroke, hemorrhagic stroke, systemic embolism
The occurence of ischaemic stroke, hemorrhagic stroke, or systemic embolism during study participation (12months) will be quantified
Measured: 12 months
Combination of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death
The occurence of major adverse cardiovascular events (MACE) including recurrent stroke, myocardial infarction and cardiovascular death during study participation (12months) will be quantified
Measured: 12 months
Combination of major and clinically relevant non-major bleedings defined according to ISTH criteria
The occurence of major and clinically relevant non-major bleedings defined according to ISTH criteria during study participation (12months) will be quantified
Measured: 12 months
Change of cognitive function (MOCA)
MOCA test will be performed upon study enrollment and 12 months after enrollment and both tests will be compared
Measured: 12 months
Life quality (EQ-5D)
EQ-5D questionnaire will be raised upon study enrollment and 12 months after enrollment and both questionnaires will be compared
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2015 (estimated)
- Study startDec 2015
- Primary completionAug 2020
- Study completionSep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Embolic Stroke of Undetermined SourceStudies of the same condition, open and under way.
- More trials run by University Hospital TuebingenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 352 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Tuebingen
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Medtronic, ZKS and IKEaB Tübingen
- Responsible party
- Sponsor
- Investigators
- Tobias Geisler, Prof, Principal investigator, Tübingen University HospitalSven Poli, Prof, Principal investigator, Tübingen University HospitalSchreieck Jürgen, Prof, Principal investigator, Tübingen University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427126
- Sponsor's protocol ID
- 2014-005109-19
- Other IDs
- 2014
- Acronym
- ATTICUS
- Status last verified
- Sep 2021
- First submitted
- 20 Mar 2015
- Last updated
- 13 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Geisler T, Keller T, Martus P, Poli K, Serna-Higuita LM, Schreieck J, Gawaz M, Tunnerhoff J, Bombach P, Nagele T, Klose U, Aidery P, Groga-Bada P, Kraft A, Hoffmann F, Hobohm C, Naupold K, Niehaus L, Wolf M, Bazner H, Liman J, Wachter R, Kimmig H, Jung W, Huber R, Feurer R, Lindner A, Althaus K, Bode FJ, Petzold GC, Nguyen TN, Mac Grory B, Schrag M, Purrucker JC, Zuern CS, Ziemann U, Poli S; ATTICUS Investigators. Apixaban versus Aspirin for Embolic Stroke of Undetermined Source. NEJM Evid. 2024 Jan;3(1):EVIDoa2300235. doi: 10.1056/EVIDoa2300235. Epub 2023 Dec 22.
PubMed 38320511
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Apixaban for Treatment of Embolic Stroke of Undetermined Source (ATTICUS Randomized Trial)
- ClinicalTrials.gov ID
- NCT02427126
- Acronym / sponsor ID
- ATTICUS / 2014-005109-19
- Conditions
- Embolic Stroke of Undetermined Source
- Keywords
- ESUS, anticoagulation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 352 participants (actual)
- Lead sponsor
- University Hospital TuebingenUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Medtronic, ZKS and IKEaB Tübingen
- Study start
- Dec 2015 (actual)
- Primary completion
- Aug 2020 (actual)
- Study completion
- Sep 2021 (actual)
- First posted
- 27 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Apixaban | Experimental | Drug: ApixabanApixaban 5mg b.i.d. Study treatment: 12 months Follow-up: 30 days after last study drug intake |
| Aspirin | Active comparator | Drug: AspirinAcetylic Salicylic Acid 100mg o.d.; Study treatment: 12 months Follow-up: 30 days after last study drug intake |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApixabanAlso: EliquisApixaban 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 | Drug | Apixaban |
| AspirinAcetylic Salicylic Acid 100mg o.d.; 12 Months | Drug | Aspirin |
Primary outcome
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.
5 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2021.
- Derived from this study: PubMed 38320511Geisler T, Keller T, Martus P, Poli K, Serna-Higuita LM, Schreieck J, Gawaz M, Tunnerhoff J, Bombach P, Nagele T, Klose U, Aidery P, Groga-Bada P, Kraft A, Hoffmann F, Hobohm C, Naupold K, Niehaus L, Wolf M, Bazner H, Liman J, Wachter R, Kimmig H, Jung W, Huber R, Feurer R, Lindner A, Althaus K, Bode FJ, Petzold GC, Nguyen TN, Mac Grory B, Schrag M, Purrucker JC, Zuern CS, Ziemann U, Poli S; ATTICUS Investigators. Apixaban versus Aspirin for Embolic Stroke of Undetermined Source. NEJM Evid. 2024 Jan;3(1):EVIDoa2300235. doi: 10.1056/EVIDoa2300235. Epub 2023 Dec 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tobias Geisler, Prof principal investigator
Tübingen University Hospital
Sven Poli, Prof principal investigator
Tübingen University Hospital
Schreieck Jürgen, Prof principal investigator
Tübingen University Hospital
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Apixaban and Aspirin in people with Embolic Stroke of Undetermined Source, run by University Hospital Tuebingen at 16 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02427126, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2021.