title: No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters.
abstract: OBJECTIVE
  This study evaluated interaction potential between sugammadex and aspirin on platelet aggregation.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, four-period crossover study in 26 healthy adult males. Treatments were i.v. placebo, i.v. sugammadex 4 mg/kg, and i.v. placebo/sugammadex with oncedaily oral aspirin 75 mg. Primary objective was to assess interaction between sugammadex and aspirin on platelet aggregation using collagen-induced whole-blood aggregometry. Effects on activated partial thromboplastin time (APTT) and cutaneous bleeding time were also evaluated. Platelet aggregation and APTT were evaluated by geometric mean ratios, using area-under-effect curves 3 - 30 minutes after sugammadex/placebo dosing. Bleeding time ratio was evaluated at 5 minutes post-dosing. Non-inferiority margins were pre-specified via literature review. Type I error was controlled using a hierarchical strategy.
  
  
  RESULTS
  Ratio for platelet aggregation for aspirin with sugammadex vs. aspirin alone was 1.01, with lower limit of two-sided 90% CI of 0.91(above non-inferiority margin of 0.75). Ratio for statistical interaction between sugammadex and aspirin on APTT was 1.01, with upper 90% CI of 1.04 (below non-inferiority margin of 1.50), and for sugammadex vs. placebo alone was 1.06, with an upper 90% CI of 1.07 (below non-inferiority margin of 1.50). Ratio for bleeding time for aspirin with sugammadex vs. aspirin plus placebo was 1.20, with upper 90% CI of 1.45 (below non-inferiority margin of 1.50). Sugammadex was generally well tolerated.
  
  
  CONCLUSIONS
  There was no clinically relevant reduction in platelet aggregation with addition of sugammadex 4 mg/kg to aspirin. Pre-determined non-inferiority margins were not exceeded for bleeding time and APTT.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: de Kam
authors.forename: Rachid
authors.initials: R
authors.lastname: El Galta
authors.forename: Annelieke C
authors.initials: AC
authors.lastname: Kruithof
authors.forename: Hein
authors.initials: H
authors.lastname: Fennema
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: van Lierop
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Mihara
authors.forename: Jacobus
authors.initials: J
authors.lastname: Burggraaf
authors.forename: Matthijs
authors.initials: M
authors.lastname: Moerland
authors.forename: Pierre
authors.initials: P
authors.lastname: Peeters
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Troyer
mesh_terms: D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000187:drug effects*; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
chemical_list: D047408:gamma-Cyclodextrins; D000077122:Sugammadex; D001241:Aspirin