Katharina Mayer1, Ralph Hein-Rothweiler2, Stefanie Schüpke1,3, Marion Janisch1, Isabell Bernlochner3,4, Gjin Ndrepepa1, Dirk Sibbing2,3,5, Tommaso Gori6,7, Oliver Borst8, Stefan Holdenrieder9, Danny Kupka2, Tobias Petzold2, Christian Bradaric4, Rainer Okrojek4, David M Leistner10,11, Tobias D Trippel11,12, Thomas Münzel6,7, Ulf Landmesser10,11, Burkert Pieske11,12, Andreas M Zeiher7,13, Meinrad P Gawaz8, Alexander Hapfelmeier14,15, Karl-Ludwig Laugwitz3,4, Heribert Schunkert1,3, Adnan Kastrati1,3, Steffen Massberg2,3. 1. Klinik für Herz- und Kreislauferkrankungen, Deutsches Herzzentrum München, Technical University of Munich, Munich, Germany. 2. Department of Cardiology, Medizinische Klinik und Poliklinik I, Munich University Clinic, Ludwig-Maximilian University of Munich, Munich, Germany. 3. German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany. 4. Medizinische Klinik und Poliklinik Innere Medizin I, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 5. Privatklinik Lauterbacher Mühle am Ostersee, Iffeldorf, Germany. 6. Department of Cardiology, University Medical Center Mainz, Mainz, Germany. 7. German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Germany. 8. Medizinische Klinik III-Kardiologie und Angiologie, Eberhard Karls University of Tübingen, Tübingen, Germany. 9. Institut für Laboratoriumsmedizin, Deutsches Herzzentrum München, Technical University of Munich, Munich, Germany. 10. Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Kardiologie, Berlin, Germany. 11. German Center for Cardiovascular Research (DZHK), Partner Site Berlin, Germany. 12. Charité-Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Kardiologie, Campus Virchow-Klinikum, Department of Internal Medicine and Cardiology, German Heart Center, Berlin, Germany. 13. Cardiology Division, Department of Medicine III, Johann Wolfgang Goethe University, Frankfurt, Germany. 14. Institute of Medical Informatics, Statistics and Epidemiology, Technical University of Munich School of Medicine, Munich, Germany. 15. Institute of General Practice and Health Services Research, Technical University of Munich School of Medicine, Munich, Germany.
Abstract
Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.
Importance: The assessment of new antithrombotic agents with a favorable safety profile is clinically relevant. Objective: To test the efficacy and safety of revacept, a novel, lesion-directed antithrombotic drug, acting as a competitive antagonist to platelet glycoprotein VI. Design, Setting, and Participants: A phase 2 randomized clinical trial; patients were enrolled from 9 centers in Germany from November 20, 2017, to February 27, 2020; follow-up ended on March 27, 2020. The study included patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous coronary intervention (PCI). Interventions: Single intravenous infusion of revacept, 160 mg, revacept, 80 mg, or placebo prior to the start of PCI on top of standard antithrombotic therapy. Main Outcomes and Measures: The primary end point was the composite of death or myocardial injury, defined as an increase in high-sensitivity cardiac troponin to at least 5 times the upper limit of normal within 48 hours from randomization. The safety end point was bleeding type 2 to 5 according to the Bleeding Academic Research Consortium criteria at 30 days. Results: Of 334 participants (median age, 67.4 years; interquartile range, 60-75.1 years; 253 men [75.7%]; and 330 White participants [98.8%]), 120 were allocated to receive the 160-mg dose of revacept, 121 were allocated to receive the 80-mg dose, and 93 received placebo. The primary end point showed no significant differences between the revacept and placebo groups: 24.4%, 25.0%, and 23.3% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .98). The high dose of revacept was associated with a small but significant reduction of high-concentration collagen-induced platelet aggregation, with a median 26.5 AU × min (interquartile range, 0.5-62.2 AU × min) in the revacept, 160 mg, group; 43.5 AU × min (interquartile range, 22.8-99.5 AU × min) in the revacept, 80 mg, group; and 41.0 AU × min (interquartile range, 31.2-101.0 AU × min) in the placebo group (P = .02), while adenosine 5'-diphosphate-induced aggregation was not affected. Revacept did not increase Bleeding Academic Research Consortium type 2 or higher bleeding at 30 days compared with placebo: 5.0%, 5.9%, and 8.6% in the revacept, 160 mg, revacept, 80 mg, and placebo groups, respectively (P = .36). Conclusions and Relevance: Revacept did not reduce myocardial injury in patients with stable ischemic heart disease undergoing percutaneous coronary intervention. There were few bleeding events and no significant differences between treatment arms. Trial Registration: ClinicalTrials.gov Identifier: NCT03312855.
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