Apixaban for Treatment of Embolic Stroke of Undetermined Source

• Status: Completed
• Trial end date: 2021-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital Tuebingen
• Collaborators: Bristol-Myers Squibb; Medtronic; ZKS and IKEaB Tübingen
• Treatments: Apixaban; Aspirin; Salicylic Acid

Criteria

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