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 | Â | ||||||
 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 | Â | ||||||
 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 | Â | ||||||
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) | ||||||