Abstract
BackgroundFresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. In the United Kingdom prothrombin complex concentrate (PCC) is not licensed in this setting, although it is being used in Europe because it has a higher concentration of clotting factor levels, and it can be administered rapidly and in small volume, resulting in less volume overload during cardiac surgery.MethodsPROPHESY is a pragmatic, single-centre, open-label, randomised, controlled pilot trial that will assess whether it is feasible to perform a large trial in the future that will compare PCC versus FFP in patients who are bleeding (not on warfarin) and who require blood transfusion. Over a 15-month period, 50 patients will be randomised to PCC versus FFP if they develop active bleeding within 24 h of cardiac surgery and for whom the clinician has decided to administer FFP for treatment of bleeding. Standard laboratory and point-of-care assessments will be performed as per routine practice, and additional research blood samples will be taken at three time points to assess haemostasis. Subjects will be assessed daily up to hospital discharge or 30 days or death (whichever occurs first) and will be seen in follow-up for 90 days after surgery to assess for thromboembolic complications and hospital re-admission since discharge. Quality-of-life assessment will be performed pre-surgery and at 90 days post-surgery. We will also perform qualitative research with clinical experts and patients to explore the understanding of and experience with the interventions, as well as adherence to study procedures and protocol.DiscussionThere have been no randomised controlled trials that have compared the safety and efficacy of FFP versus PCC in cardiac surgery patients who are bleeding. This pilot study will assess if individual components of a large trial are deliverable to assess the safety and efficacy of the two blood products in the future.Trial registrationEudraCT, 2018-003041-41; ClinicalTrials.gov, NCT03715348. Registered on 29 July 2018.
Highlights
Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery
Clinical equipoise and the lack of high-quality evidence means that an randomised controlled trials (RCT) is required to determine how prothrombin complex concentrate (PCC) compares with FFP
Randomisation process The pragmatic nature of the study means that the decision whether to administer the intervention will be based on clinicians’ judgement, so that when a patient is actively bleeding within 24 h of surgery and a clinician has decided that FFP is needed to treat the bleeding, the patient will be randomised by the transfusion laboratory to either a single dose of FFP or 4-factor PCC using a web-based electronic database
Summary
Fresh frozen plasma (FFP) is the accepted standard treatment for clotting factor replacement in bleeding patients during or immediately after cardiac surgery. The national comparative audit in the United Kingdom in 2011, which incorporated data from 66% of all UK cardiac centres, showed that the overall blood transfusion rate was high across all procedures, with fresh frozen plasma (FFP) being administered in over 20% of patients undergoing valve replacement or repair surgeries and in 30% of patients undergoing combined coronary artery bypass graft + valve repair/replacement surgeries [2]. Taking into consideration that blood transfusion is not without risks, other haemostatic agents, such as prothrombin complex concentrate (PCC), are being explored by clinicians for management of bleeding, including in the peri-operative phase for patients undergoing cardiac surgery. Potential advantages of PCC over FFP include increased concentration of clotting factors leading to faster and more sustained reversal of coagulopathy, improved ease and speed of administration, reduced fluid volume (20–40 ml compared with up to 1000 ml with FFP), and reduced incidence of immunomodulatory side effects
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call