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Table 2 Randomised studies in healthy volunteers

From: The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review

Study Design N DOAC PCC Results
Laboratory parameters tested Reversal of DOAC effects with PCC Bleeding
Barco et al. [58] Randomised, double-blind, placebo-controlled, crossover 6 Rivaroxaban (15 mg BID) 4F-PCC (Cofact® 25 or 37.5 IU/kg) PT (+) with both doses of 4F-PCC No deaths, SAEs or TEEs reported
ETP (+) with 4F-PCC 37.5 IU/kg
Brown et al. [60] Randomised, double-blind, placebo-controlled, three-way crossover 24 Edoxaban (60 or 120 mg) 3F-PCC (Bebulin® 25 or 50 IU/kg) PT (−) No deaths, SAEs or TEEs reported
ETP (+)
Cheung et al. [61] Randomised, double-blind, placebo-controlled, crossover 6 Apixaban (10 mg BID) 4F-PCC (Cofact® 25 or 37.5 IU/kg) PT (+) No deaths, SAEs or TEEs reported
ETP Partial
Eerenberg et al. [9] Randomised, double-blind, placebo-controlled, crossover 12 Dabigatran (150 mg BID) 4F-PCC (Cofact® 50 IU/kg) TGA lag time, aPTT, ECT, TT (−) No deaths, SAEs or TEEs reported
Rivaroxaban (20 mg BID) PT, ETP (+)
Levi et al. [57] Randomised, open-label, parallel-group 35 Rivaroxaban (20 mg BID) 4F-PCC (Beriplex® 50 IU/kg) and 3F-PCC (Profilnine® 50 IU/kg) PT (+) 4F-PCC > 3F-PCC No deaths, SAEs or TEEs reported
TGA  
 ETP (+) 3F-PCC > 4F-PCC
 Peak TG (+) with 3F-PCC only
 Time to peak (+)
 Lag time (-)
aPTT (-)
Levy et al. [59] Randomised, double-blind, parallel-group 147 Rivaroxaban (20 mg BID) 4F-PCC (Kcentra® 50 IU/kg) PT Partial No deaths, SAEs or TEEs reported; no difference from saline control in reversal of effects on bleeding duration and volume after administration of 4F-PCC or TXA
TGA  
 ETP (+)
Nagalla et al. [63] Randomised, two-period crossover, assessor-blinded 12 Apixaban
(5 mg BID)
4F-PCC (Kcentra®/Beriplex®
25 IU/kg)
PT (+) No deaths, SAEs or TEEs reported
TGA parameters (peak, lag time, ETP) (+) (significan\ce dependent on reagents used)
TGA parameters (time to peak, maximum velocity) (-)
aPTT (-)
Song et al. [62] Open-label, randomised, placebo-controlled, 3-period crossover 15 Apixaban (10 mg BID) 4F-PCC (Beriplex® or Cofact® 50 IU/kg) TGA (+) No deaths, SAEs or TEEs reported
 ETP (+)
 Peak height (-)
 Lag time (-)
 Time to peak (-)
 Velocity index (+)
PT  
Zahir et al. [30] Randomised, double-blind, placebo-controlled, two-sequence, two-period, crossover 93 Edoxaban (60 mg) 4F-PCC (Beriplex® 10, 25 or 50 IU/kg) PT Partial with 4F-PCC 50 IU/kg No deaths, SAEs or TEEs reported; reversal of effects on bleeding duration and volume (with 50 IU/kg; partial reversal with 25 IU/kg)
ETP (+) with 50?IU/kg (partial with 25?IU/kg)
  1. (−), negative result; (+), positive result. 3F-PCC three-factor prothrombin complex concentrate, 4F-PCC four-factor prothrombin complex concentrate, aPCC activated prothrombin complex concentrate, aPTT activated partial thromboplastin time, BID bis in die (twice daily), ECT ecarin clotting time, ETP endogenous thrombin potential, PT prothrombin time, TG thrombin generation, TGA thrombin generation assay, TT thrombin time, TXA tranexamic acid