Apixaban for Treatment of Embolic Stroke of Undetermined Source

Embolic Stroke of Undetermined Source Clinical Trial

— ATTICUS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02427126
• Other study ID #: 2014-005109-19
• Status: Completed
• Phase: Phase 3
• Start date: December 2015
• Est. completion date: September 2021

Study information

• Verified date: September 2021
• Source: University Hospital Tuebingen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 352
• Est. completion date: September 2021
• Est. primary completion date: August 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Embolic Stroke
• Embolic Stroke of Undetermined Source
• Stroke

Intervention

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
• Aspirin
Acetylic Salicylic Acid 100mg o.d.; 12 Months

Locations

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

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital Tuebingen	Bristol-Myers Squibb, Medtronic, ZKS and IKEaB Tübingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months
Secondary	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	12 months
Secondary	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	12 months
Secondary	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	12 months
Secondary	Change of cognitive function (MOCA)	MOCA test will be performed upon study enrollment and 12 months after enrollment and both tests will be compared	12 months
Secondary	Life quality (EQ-5D)	EQ-5D questionnaire will be raised upon study enrollment and 12 months after enrollment and both questionnaires will be compared	12 months