{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T19:52:05Z","timestamp":1782762725390,"version":"3.54.5"},"reference-count":22,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":60,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TH Open"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Patients with stroke or transient ischemic attacks (TIAs) and internal carotid artery stenosis harbor an increased risk of recurrent stroke especially within 2 weeks after the first event. In addition, the revascularization procedure itself (carotid endarterectomy [CEA] or carotid artery stenting [CAS]) is associated with both clinically apparent and silent brain infarctions, mainly caused by the embolic nature of the ruptured carotid plaque. The glycoprotein VI (GPVI) fusion protein Revacept is a highly specific antithrombotic drug without direct inhibition of systemic platelet function that might reduce periprocedural distal embolization from the vulnerable ruptured plaque located at the internal carotid artery. By shielding collagen at the site of vascular injury, Revacept inhibits plaque-mediated platelet adhesion and aggregation, while not directly affecting systemic hemostasis. In this phase II study, 158 patients with symptomatic carotid artery stenosis with recent TIA or stroke were randomized to receive a single dose of either Revacept (40 or 120\u2009mg) or placebo. All patients were on standard secondary preventive therapy (statins and platelet inhibition) and underwent CEA, CAS, or best medical therapy according to current guidelines. The efficacy of Revacept was evaluated by exploratory assessment of new diffusion-weighted imaging lesions on magnetic resonance imaging after the revascularization procedure; a combination of cardiovascular events (ischemic and hemorrhagic stroke, TIA, myocardial infarction, or coronary intervention) and bleeding complications served to assess clinically critical patients' outcome and safety. This exploratory phase II randomized, double-blind clinical trial provides valuable insights on the safety, tolerability, and efficacy of Revacept in patients with symptomatic carotid artery stenosis.<\/jats:p>","DOI":"10.1055\/s-0040-1721078","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T19:41:33Z","timestamp":1606765293000},"page":"e393-e399","source":"Crossref","is-referenced-by-count":20,"title":["Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Artery Stenosis: Design and Rationale of a Randomized Phase II Clinical Trial"],"prefix":"10.1055","volume":"04","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0244-6116","authenticated-orcid":false,"given":"Klaus","family":"Gr\u00f6schel","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Uphaus","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Loftus","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, St George's University Hospitals NHS Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Poppert","sequence":"additional","affiliation":[{"name":"Department of Neurology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Christoph","family":"Diener","sequence":"additional","affiliation":[{"name":"Institute for Medical Informatics, Biometry and Epidemiology, Medical Faculty of the University Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Zobel","sequence":"additional","affiliation":[{"name":"advanceCOR, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00f6tz","family":"M\u00fcnch","sequence":"additional","affiliation":[{"name":"advanceCOR, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1212\/01.WNL.0000110311.09970.83","article-title":"Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies","volume":"62","author":"J K Lovett","year":"2004","journal-title":"Neurology"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1212\/01.WNL.0000170368.82460.b4","article-title":"Population-based study of delays in carotid imaging and surgery and the risk of recurrent stroke","volume":"65","author":"J F Fairhead","year":"2005","journal-title":"Neurology"},{"issue":"09","key":"ref3","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1093\/eurheartj\/ehx095","article-title":"2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries endorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS)","volume":"39","author":"V Aboyans","year":"2018","journal-title":"Eur Heart J"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/S0140-6736(10)61009-4","article-title":"Short-term outcome after stenting versus endarterectomy for symptomatic carotid stenosis: a preplanned meta-analysis of individual patient data","volume":"376","author":"L H Bonati","year":"2010","journal-title":"Lancet"},{"issue":"05","key":"ref5","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/j.jvs.2015.12.020","article-title":"Dual antiplatelet therapy reduces stroke but increases bleeding at the time of carotid endarterectomy","volume":"63","author":"D W Jones","year":"2016","journal-title":"J Vasc Surg"},{"issue":"09","key":"ref6","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.jacc.2003.12.039","article-title":"Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting: risk factors, prevention, and treatment","volume":"43","author":"A Abou-Chebl","year":"2004","journal-title":"J Am Coll Cardiol"},{"issue":"06","key":"ref7","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1161\/CIRCULATIONAHA.118.036248","article-title":"Major bleeding rates in atrial fibrillation patients on single, dual, or triple antithrombotic therapy","volume":"139","author":"N van Rein","year":"2019","journal-title":"Circulation"},{"issue":"11","key":"ref8","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.jacc.2009.11.051","article-title":"A 2-step mechanism of arterial thrombus formation induced by human atherosclerotic plaques","volume":"55","author":"A J Reininger","year":"2010","journal-title":"J Am Coll Cardiol"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1182\/blood-2002-12-3882","article-title":"Platelet-collagen interaction: is GPVI the central receptor?","volume":"102","author":"B Nieswandt","year":"2003","journal-title":"Blood"},{"issue":"03","key":"ref10","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.yjmcc.2010.04.009","article-title":"Impact of glycoprotein VI and platelet adhesion on atherosclerosis\u2014a possible role of fibronectin","volume":"49","author":"A B\u00fcltmann","year":"2010","journal-title":"J Mol Cell Cardiol"},{"issue":"07","key":"ref11","doi-asserted-by":"crossref","first-page":"C757","DOI":"10.1152\/ajpcell.00060.2012","article-title":"The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice","volume":"303","author":"T Sch\u00f6nberger","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"issue":"07","key":"ref12","doi-asserted-by":"crossref","first-page":"e66960","DOI":"10.1371\/journal.pone.0066960","article-title":"The GPVI-Fc fusion protein Revacept improves cerebral infarct volume and functional outcome in stroke","volume":"8","author":"S Goebel","year":"2013","journal-title":"PLoS One"},{"issue":"02","key":"ref13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1096\/fj.03-0464fje","article-title":"Soluble glycoprotein VI dimer inhibits platelet adhesion and aggregation to the injured vessel wall in vivo","volume":"18","author":"S Massberg","year":"2004","journal-title":"FASEB J"},{"issue":"17","key":"ref14","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1161\/CIRCULATIONAHA.110.980623","article-title":"Novel antiplatelet drug Revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans","volume":"123","author":"M Ungerer","year":"2011","journal-title":"Circulation"},{"issue":"04","key":"ref15","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1161\/ATVBAHA.118.310955","article-title":"Novel antiplatelet therapies for atherothrombotic diseases","volume":"39","author":"A Majithia","year":"2019","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.jacc.2014.11.038","article-title":"Ischemic brain lesions after carotid artery stenting increase future cerebrovascular risk","volume":"65","author":"H Gensicke","year":"2015","journal-title":"J Am Coll Cardiol"},{"issue":"07","key":"ref17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.jacc.2007.10.040","article-title":"Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point","volume":"51","author":"G Ndrepepa","year":"2008","journal-title":"J Am Coll Cardiol"},{"issue":"08","key":"ref18","doi-asserted-by":"crossref","first-page":"e71193","DOI":"10.1371\/journal.pone.0071193","article-title":"The GPVI-Fc fusion protein Revacept reduces thrombus formation and improves vascular dysfunction in atherosclerosis without any impact on bleeding times","volume":"8","author":"M Ungerer","year":"2013","journal-title":"PLoS One"},{"issue":"22","key":"ref19","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1016\/j.jacc.2015.03.573","article-title":"Differential inhibition of human atherosclerotic plaque-induced platelet activation by dimeric GPVI-Fc and Anti-GPVI antibodies: functional and imaging studies","volume":"65","author":"J Jamasbi","year":"2015","journal-title":"J Am Coll Cardiol"},{"issue":"12","key":"ref20","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJMoa0905561","article-title":"Dabigatran versus warfarin in patients with atrial fibrillation","volume":"361","author":"S J Connolly","year":"2009","journal-title":"N Engl J Med"},{"issue":"17","key":"ref21","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1161\/01.CIR.0000163561.90680.1C","article-title":"Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial","volume":"111","author":"H S Markus","year":"2005","journal-title":"Circulation"},{"issue":"04","key":"ref22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S1474-4422(10)70057-0","article-title":"New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS)","volume":"9","author":"L H Bonati","year":"2010","journal-title":"Lancet Neurol"}],"container-title":["TH Open"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1721078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T19:42:16Z","timestamp":1606765336000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1721078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10]]},"references-count":22,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2020,11,19]]},"published-print":{"date-parts":[[2020,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1721078","relation":{},"ISSN":["2512-9465"],"issn-type":[{"value":"2512-9465","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10]]}}}