Revacept in Symptomatic Carotid Stenosis (Revacept/CS/02)

Inclusion Criteria:

1. Signed written informed consent

2. Target population

   • Diagnosis:

     • Extracranial carotid artery stenosis (diagnosed by vascular duplex ultrasound peak flow or angiography)
     • Lesions with ≥ 50 % stenosis according to the European Carotid Surgery Trial (ECST) criteria
     • MES detected by TCD (greater than or equal to 1 MES per hour)
     • Ipsilateral TIA, amaurosis fugax or stroke within the last 30 days
   • Age and sex: Men and women aged > 18 years Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after receiving investigational product in such a manner that the risk of pregnancy is minimised.

Exclusion Criteria:

1. Sex and reproductive Status:

   • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for up to 4 weeks after receiving investigational product.
   • Women who are pregnant or breastfeeding
   • Women with a positive pregnancy test on enrollment or prior to investigational product administration.

2. Target disease exceptions

   • Ipsilateral siphon or middle cerebral artery stenosis (tandem stenosis)
   • NIHSS score > 18
   • Recent intracerebral haemorrhage by X-ray computed tomography (CT) or nuclear magnetic resonance (NMR)
   • Cardiac cause of embolisation (atrial fibrillation or other cardiac source e.g. artificial heart valves)

3. Medical history and concurrent disease

   • History of hypersensitivity, contraindication or serious adverse reaction to inhibitors of platelet aggregation, hypersensitivity to related drugs (cross-allergy) or to any of the excipients in the study drug
   • History or evidence of thrombocytopenia (<30.000/ul), bleeding diathesis or coagulopathy (pathological international normalised ratio (INR) or activated partial thromboplastin time (aPTT))
   • Thrombolysis within the last 48 hours
   • Relevant haemorrhagic transformation as determined by CT, NMR or anamnesis
   • Oral anticoagulation or other anti-platelet therapy than aspirin or clopidogrel within the last 3 weeks (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat)
   • Sustained hypertension (systolic BP > 179 mmHg or diastolic BP >109 mmHg), hypertensive patients shall be treated in accordance with current guidelines for the management of arterial hypertension
   • History of severe systemic disease such as terminal carcinoma, renal failure (or current creatinine > 200 umol/l), cirrhosis, severe dementia, or psychosis
   • Current severe liver dysfunction (transaminase level greater than 5-fold over upper normal range limit)
   • Active autoimmune disorder such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis or glomerulonephritis
   • Known atrial fibrillation or other clinically significant ECG abnormalities (at present)

4. Prohibited Treatments and/or therapies

   • Oral anticoagulation or dual antiplatelet therapy (aspirin combined with clopidogrel or other P2Y inhibitors) within the last 3 weeks; dipyridamole extended release within last 3 days; tirofiban/Aggrastat within the last 8 hours
   • Indication for oral anticoagulation