Thromb Haemost 2019; 119(09): 1539-1545
DOI: 10.1055/s-0039-1692423
Trial Protocol Design Paper
Georg Thieme Verlag KG Stuttgart · New York

Revacept, a Novel Inhibitor of Platelet Adhesion, in Patients Undergoing Elective PCI—Design and Rationale of the Randomized ISAR-PLASTER Trial

Stefanie Schüpke*
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Ralph Hein-Rothweiler*
3  Department of Cardiology, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
,
Katharina Mayer
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
,
Marion Janisch
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
,
Dirk Sibbing
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
3  Department of Cardiology, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
,
Gjin Ndrepepa
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
,
Raphaela Hilz
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
,
Karl-Ludwig Laugwitz
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
4  Medizinische Klinik und Poliklinik Innere Medizin I (Kardiologie, Angiologie, Pneumologie), Klinikum rechts der Isar, Munich, Germany
,
Isabell Bernlochner
4  Medizinische Klinik und Poliklinik Innere Medizin I (Kardiologie, Angiologie, Pneumologie), Klinikum rechts der Isar, Munich, Germany
,
Sarah Gschwendtner
3  Department of Cardiology, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
,
Danny Kupka
3  Department of Cardiology, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
,
Tommaso Gori
5  Zentrum für Kardiologie, University Hospital Mainz, Mainz, Germany
6  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany
,
Andreas M. Zeiher
6  German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany
7  Cardiology Division, Department of Medicine III, Johann Wolfgang Goethe University, Frankfurt, Germany
,
Heribert Schunkert
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
Steffen Massberg*
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
3  Department of Cardiology, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany
,
Adnan Kastrati*
1  Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany
2  German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
,
for the ISAR-PLASTER-Trial Investigators› Author Affiliations
Funding Funding is granted by the German Center for Cardiovascular Research (DZHK), Deutsches Herzzentrum München, Federal Ministry of Education and Research (BMBF), and advanceCOR GmbH (the manufacturer of Revacept).
Further Information

Publication History

28 February 2019

17 April 2019

Publication Date:
21 June 2019 (eFirst)

Abstract

Despite dual antiplatelet therapy patients undergoing percutaneous coronary intervention (PCI) continue to experience periprocedural ischemic events. In addition, all currently used antithrombotic drugs increase the bleeding risk. Thus, there is an unmet clinical need for antithrombotic strategies with improved efficacy and no increase in bleeding. Revacept is a novel, lesion-directed antithrombotic drug that does not interfere with the function of circulating platelets. This dimeric fusion protein of the extracellular domain of glycoprotein VI (the major platelet collagen receptor) and the human Fc-fragment inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. The randomized, double-blinded, phase II ISAR-PLASTER trial is based on extensive preclinical evaluation of Revacept and a favorable first-in-man trial. A total of 332 patients with stable coronary artery disease undergoing elective PCI will be randomized to either Revacept 160 mg, Revacept 80 mg, or placebo administered as single intravenous infusion directly before the intervention, on top of standard dual antiplatelet therapy and either heparin or bivalirudin, based on local practice and current guidelines. The primary endpoint is the composite of death or myocardial injury (defined as increase in high sensitivity troponin T ≥ 5 times the upper limit of normal) at 48 hours. The safety endpoint is bleeding of class 2 or higher according to the Bleeding Academic Research Consortium at 30 days. This phase II randomized, double blind trial will assess for the first time the efficacy and safety of Revacept—a lesion-directed inhibitor of platelet adhesion—in patients undergoing elective PCI.

Clinical Trial Registration Information

URL www.clinicaltrials.gov; Unique identifier NCT03312855.


* These authors contributed equally to the study.


Supplementary Material