Table 1 Characteristics of included randomised clinical trials
Trial | Boulis et al | Sarode et al | Steiner et al | Shadvar et al | Connolly et al |
|---|---|---|---|---|---|
Year | 1999 | 2013 | 2016 | 2021 | 2024 |
Trial characteristics | |||||
Number of trial sites | 1 | 36 | 5 | ND | 131 |
Current anticoagulation treatment on admission | |||||
VKA | 21 | 216 | 54 | 0 | 0 |
DOAC | 0 | 0 | 0 | 41 | 530* |
Biochemical criteria for inclusion | PT > 17 s at the time of randomisation | INR ≥ 2.0 within 3 h before study treatment | Admission INR ≥ 2.0 | None | None |
Population | Intracranial haemorrhage | Major bleeding | Spontaneous intracerebral or subdural haemorrhage | Major bleeding | Intracranial haemorrhage |
Intervention | |||||
PCC | 4-factor, not activated, PCC (Konyne, Bayer, Elkhart, Indiana, USA) | 4-factor, not activated, PCC (Beriplex P/N, CSL Behring, Marburg, Germany) | 4-factor, not activated, PCC (Octaplex, Octapharma, Lachen, Switzerland) | 4-factor, not activated, PCC (Octaplex, Octapharma, Canada) | At the discretion of the investigator |
Control | No intervention | Fresh frozen plasma | Fresh frozen plasma | Fresh frozen plasma | Andexanet alfa |
Co-interventions | 10Â mg subcutaneous vitamin K and fresh frozen plasma at the maximum tolerated dose | 5 to 10Â mg intravenous vitamin K (or according to local guidelines) | 10Â mg intravenous vitamin K | None | None |
Rescue intervention | None | None | PCC administration in both intervention arms if INR > 1.2 at 3 h after first intervention | An additional dose of PCC in those allocated to PCC or an additional dose of fresh frozen plasma in those allocated to fresh frozen plasma | At the discretion of the investigator |
Protocol or prospective registration available | No | Yes | Yes | Yes | Yes |
Allocation in trial | |||||
Allocated to PCC (no. of participants) | 8 | 107 | 28 | 20 | 230 |
Allocated to control (no. of participants) | 13 | 109 | 26 | 21 | 263 |
Risk of bias assessment†| |||||
Allocation sequence generation | Unclear risk | Low risk | Low risk | Unclear risk | Low risk |
Allocation concealment | Unclear risk | Low risk | Low risk | Unclear risk | Low risk |
Blinding of participants and treatment providers | High risk | High risk | High risk | Unclear risk | High risk |
Blinding of outcome assessors | High risk | Low risk | Low risk | Unclear risk | Low risk |
Incomplete outcome data | High risk | Low risk | Low risk | Unclear risk | High risk |
Selective outcome reporting | Unclear risk | Unclear risk | Low risk | Unclear risk | Low risk |
Vested interest bias | Unclear risk | High risk | High risk | Unclear risk | High risk |