Revacept in Symptomatic Carotid Stenosis

Study Overview
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Brief Summary
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Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks (TIAs), amaurosis fugax or stroke receive either Revacept (single dose) plus antiplatelet monotherapy or monotherapy alone. Patients receive a single dose of trial medication by intravenous infusion for 20 minutes. Patients are followed up one and three days after treatment, at 3 months and by a telephone interview at 12 months.

Detailed Description
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Patients had a more than 50% carotid artery stenosis according to ECST and suffered from ischemic stroke, transitory ischemic attack or intermittent blindness (amaurosis fugax) within the last 30 days. All patients were on standard medication with aspirin or clopidogrel and received heparin for thrombosis prophylaxis. Carotid endarterectomy (CEA), carotid stenting (CAS) or best medical therapy for treatment of the carotid stenosis and prevention of secondary thrombo-emboli was performed according to guidelines. Additional treatment with Revacept or placebo was done on top of the standard therapy. Therefore the control group receiving placebo was already on the standard medical therapy for patients with symptomatic carotid stenosis and received also the guideline conform interventions CEA, CAS or best medical therapy. Secondary prophylaxis of thrombo-embolic ischemic events by Revacept should be investigated. Therefore microemboli were detected by transcranial Doppler and ischemic brain lesions were investigated by diffusion weighted imaging magnetic resonance imaging (DWI-MRI) scan as exploratory endpoints. Moreover clinical endpoints such as stroke, TIA, myocardial infarction, coronary intervention and death were investigated at 1 week, 3 months and 12 months follow-up. Safety was closely monitored with emphasis on bleeding complications as bleeding is the most dreaded complication of anti-thrombotic agents especially in patients with cerebral strokes.

Official Title
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Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Stenosis: A Phase II, Multicentre; Randomised, Dose-finding, Double-blind and Placebo Controlled Superiority Study With Parallel Groups

Conditions
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Atherosclerosis, TIA, Carotid Stenosis, Stroke, Transient-ischaemic Attack, Amaurosis Fugax

Intervention / Treatment
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* Drug: Revacept
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent 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 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: 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. Target disease exceptions 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) 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 dual anti-platelet therapy with aspirin or clopidogrel and other P2Y inhibitors at screening (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat) Sustained hypertension (systolic BP > 179 mmHg or diastolic BP >109 mmHg) 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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Phosphate buffered saline (PBS), 1% sucrose, 4% mannitol<br>Placebo control with PBS, 1% sucrose and 4% mannitol | Drug: Placebo<br>* single intravenous injection<br>* Other names: Control Group;|
| Active Comparator: 40 mg Revacept<br>low dose Revacept 40mg in PBS, 1% sucrose, 4% mannitol | Drug: Revacept<br>* single intravenous injection<br>* Other names: 40 mg or 120 mg;|
| Active Comparator: 120 mg Revacept<br>high dose revacept 120mg in PBS, 1% sucrose, 4% mannitol | Drug: Revacept<br>* single intravenous injection<br>* Other names: 40 mg or 120 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New DWI Lesion(s) | The number of new diffusion weighted imaging (DWI) lesion(s) reported. (1 day after intervention compared to baseline). | 1 day post intervention |