Revacept, an Inhibitor of Platelet Adhesion in Symptomatic Carotid Artery Stenosis: Design and Rationale of a Randomized Phase II Clinical Trial.

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 mg) 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.

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The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).

Déclaration de conflit d'intérêts

Conflict of Interest In the past 3 years H.C.D. received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from: Abbott, Bayer Vital, BMS, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Pfizer, Portola, Sanofi-Aventis and WebMD Global. Financial support for research projects was provided by Boehringer Ingelheim. H.C.D. received research grants from the German Research Council (DFG), German Ministry of Education and Research (BMBF), European Union, NIH, Bertelsmann Foundation and Heinz-Nixdorf Foundation. H.C.D. served as editor of Neurologie up2date, Info Neurologie & Psychiatrie, Arzneimitteltherapie, as co-editor of Cephalalgia and on the editorial board of Lancet Neurology. H.C.D. chairs the Treatment Guidelines Committee of the German Society of Neurology and contributed to the EHRA and ESC guidelines for the treatment of AF. G.M. is employed by advanceCOR and owns shares of advanceCOR. K.G., T.U., I.L., and H.P. declared no conflict of interest.