PROthrombin complex concentrate versus fresh frozen Plasma for bleeding in adults undergoing HEart SurgerY (PROPHESY-2 trial): a phase III, randomised control trial in England and Wales

BACKGROUND: Fresh frozen plasma (FFP) is the standard treatment for severe bleeding following cardiac surgery. Despite increasing use of prothrombin complex concentrate (PCC) for coagulopathic bleeding in preference to FFP in the UK, the evidence comparing FFP versus PCC in this setting is lacking. HYPOTHESIS: In adults who develop severe bleeding, PCC is superior to FFP in reducing a composite of mortality, organ failure, or infection up to 90 days following cardiac surgery, and is more cost-effective. METHODS: Phase III pragmatic, multicentre, parallel group, superiority, non-blinded, open-label, two-stage group sequential randomised controlled trial with internal pilot embedded. Participants will be recruited by the research team at up to 20 hospitals in England and Wales. Those who have provided informed consent and who develop bleeding within 24 h of cardiac surgery (elective and urgent procedures) will be randomised to PCC (1500 IU if ≤70 kg or 2000 IU if >70 kg; a maximum of 2 doses) or FFP (4 units if ≤70 kg and 5 units if >70 kg; no maximum dose). Randomisation will be stratified by site and will allocate participants using minimisation, with a 1:1 ratio to receive PCC or FFP. Age (≥70 and