Ciraparantag safely and completely reverses the anticoagulant effects of low molecular weight heparin.

Autor: Ansell JE; Hofstra North Shore/LIJ School of Medicine, Hempstead, NY, United States., Laulicht BE; Perosphere Inc., Danbury, CT, United States., Bakhru SH; Perosphere Inc., Danbury, CT, United States., Hoffman M; Duke University School of Medicine, United States., Steiner SS; Perosphere Inc., Danbury, CT, United States., Costin JC; Perosphere Inc., Danbury, CT, United States. Electronic address: j.costin@perosphere.com.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2016 Oct; Vol. 146, pp. 113-118. Date of Electronic Publication: 2016 Jul 18.
DOI: 10.1016/j.thromres.2016.07.008
Abstrakt: Major bleeding with low molecular weight heparin (LMWH) therapy occurs in up to 5% of patients and its anticoagulation is only partially reversed by protamine sulfate. We studied the ability of ciraparantag (PER977), a novel agent that reverses LMWH in preclinical studies, to reverse LMWH in healthy volunteers.
Methods: In this phase 1/2 trial, 4 cohorts of 10 healthy volunteers received escalating doses of ciraparantag (100 to 300mg) or placebo (8:2 ratio) approximately 4h after a single subcutaneous dose of enoxaparin, 1.5mg/kg. Safety, pharmacokinetic and pharmacodynamic effects were assessed.
Results: Complete reversal of enoxaparin anticoagulation, measured by a reduction of whole blood clotting time, was observed in all subjects who received a single ciraparantag dose ranging from 100mg to 300mg. The anticoagulation reversal occurred rapidly after bolus injection and persisted for the duration of the study. At 12h and 24h, the differences in whole blood clotting time in the treated group compared to placebo were no longer significant, consistent with the decline in enoxaparin concentrations and anticoagulation effects. No procoagulant signals were detected as measured by D-dimer, F1.2, and tissue factor pathway inhibitor levels. Ciraparantag was well tolerated with only transient, minor side effects.
Conclusion: Ciraparantag reverses the whole blood clotting time induced by enoxaparin in a dose related manner and produces no procoagulant signal or deleterious adverse events in doses up to 300mg.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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