Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction
| Autor: | Ohad S. Bentur, Christopher B. Granger, Barry S. Coller, Jurriën M. ten Berg, Anne H. Tavenier, Arnoud W J van 't Hof, Rita Lobatto, W L Bor, C. Michael Gibson, Sonja Postma, Kai L Zheng |
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| Přispěvatelé: | Cardiologie, MUMC+: MA Med Staf Spec Cardiologie (9), RS: Carim - H01 Clinical atrial fibrillation, RS: Carim - B04 Clinical thrombosis and Haemostasis |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Platelet Function Tests adjunctive pharmacotherapy IMPACT PERCUTANEOUS CORONARY INTERVENTION PRIMARY ANGIOPLASTY Platelet Glycoprotein GPIIb-IIIa Complex Gastroenterology Article STEMI Subcutaneous injection Pharmacokinetics Internal medicine PREHOSPITAL INITIATION Medicine Humans ALPHA-IIB-BETA-3 ANTAGONIST TICAGRELOR TIROFIBAN Myocardial infarction clinical trials ANTIPLATELET THERAPY business.industry THROMBOCYTOPENIA 2017 ESC Tirofiban medicine.disease innovation Treatment Outcome Tolerability clinical research Pharmacodynamics ST Elevation Myocardial Infarction Cardiology and Cardiovascular Medicine business Glycoprotein IIb/IIIa Ticagrelor Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Eurointervention, 17(5), 401-410. Europa Digital & Publishing EuroIntervention |
| ISSN: | 1774-024X |
| Popis: | Background: Pre-hospital platelet inhibition in patients with ST-segment elevation myocardial infarction (STEMI) may improve outcomes. RUC-4 is a novel, second-generation glycoprotein IIb/IIIa inhibitor designed for first-point-of-medical-contact treatment for STEMI by subcutaneous injection.Aims: The open-label, phase 2A, CEL-02 trial aimed to assess the pharmacodynamics (PD), pharmacokinetics (PK), and tolerability of RUC-4 in STEMI patients undergoing primary PCI (pPCI).Methods: A total of 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before pPCI in escalating doses (0.075 mg/kg [n = 8], 0.090 mg/kg [n = 9], or 0.110 mg/kg [n = 10]).Results: The primary PD endpoint of high-grade (>= 77%) inhibition of the VerifyNow iso-TRAP assay at 15 minutes was met in 3/8, 7/8, and 7/8 patients in the three cohorts with a dose-response relationship (mean inhibition [min -max] of 77.5% [65.7%-90.6%], 87.5% [73.8%-93.1%], and 91.7% [76.4%-99.3%], respectively; ptrend = 0.002). Fifty percent (50%) inhibition remained after 89.1 (38.0-129.7), 104.2 (17.6-190.8), and 112.4 (19.7-205.0) minutes. Injection site reactions or bruising were observed in 1 (4%) and 11 (41%) patients, respectively. Mild access-site haematomas occurred in 6 (22%), and severe access-site haematomas occurred in 2 patients (7%). No thrombocytopaenia was observed within 72 hours post dose.Conclusions: In patients with STEMI, a single subcutaneous dose of RUC-4 at 0.075, 0.090, and 0.110 mg/kg showed dose-response high-grade inhibition of platelet function within 15 minutes. |
| Databáze: | OpenAIRE |
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