title: Ciraparantag safely and completely reverses the anticoagulant effects of low molecular weight heparin.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hofstra North Shore/LIJ School of Medicine, Hempstead, NY, United States.
authors.forename: Jack E
authors.initials: JE
authors.lastname: Ansell
authors.affiliation: Perosphere Inc., Danbury, CT, United States.
authors.forename: Bryan E
authors.initials: BE
authors.lastname: Laulicht
authors.affiliation: Perosphere Inc., Danbury, CT, United States.
authors.forename: Sasha H
authors.initials: SH
authors.lastname: Bakhru
authors.affiliation: Duke University School of Medicine, United States.
authors.forename: Maureane
authors.initials: M
authors.lastname: Hoffman
authors.affiliation: Perosphere Inc., Danbury, CT, United States.
authors.forename: Solomon S
authors.initials: SS
authors.lastname: Steiner
authors.affiliation: Perosphere Inc., Danbury, CT, United States. Electronic address: j.costin@perosphere.com.
authors.forename: James C
authors.initials: JC
authors.lastname: Costin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D064368:Healthy Volunteers; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D010879:Piperazines; D001120:Arginine; C000593571:PER977
keywords: Anticoagulant reversal; Ciraparantag; Low molecular weight heparin; NOACs; PER977; Whole blood clotting time