It is generally well-known, the advantages of Prothrombin Concentrate Complexes over Fresh Frozen Plasma. They are a smaller-volume infusion, more rapidly reverse the anticoagulant effect, and lack some of other disadvantages of hemostatic product use. This study, therefore, a Phase 3b open-label trial of PCCs vs. FFP for anticoagulation reversal before urgent surgery, is essentially of questionable utility. Is it emergency surgery? Then use the immediate reversal agent. Is it semi-elective? Well, why not wait a bit?
So, why even run a trial for the use of PCCs in the non-emergent realm? Well, it rapidly becomes clear how this study was conceived by review of the “Role of the funding source”:
This research was funded by CSL Behring. A steering committee of academic medical experts and representatives of the funder oversaw the design and conduct of the study. The funder participated in the selection of the board members. The funder was responsible for data collection, management, and analysis of the data according to a predefined statistical analysis plan. Preparation and review of the Article and the decision to submit for publication was done by a publication steering committee that included academic medical experts and representatives of the funder. Medical writing assistance was paid for by the funder. JNG and RS had full access to all the data in the study and took responsibility for the integrity and accuracy of the data analysis.
The goal: “indication creep” – an entirely obvious corporate landgrab, essentially sponsored, conducted, and written by CSL Behring to expand the use of PCCs beyond emergency reversal. Indeed, it’s hard to even dignify this Lancet content with a summary. The exclusion criteria were extensive. The trial was modified after a letter from the FDA. Some of the reported outcome numbers in the paper don’t match their ClinicalTrials.gov entry. Almost all the differences in outcomes were subjective or surrogates for patient-oriented measures. The authors conclusion:
“[T]hese data show that 4F-PCC is an effective and superior alternative to plasma in terms of haemostatic efficacy and rapid INR reduction for the rapid reversal of VKA therapy before urgent procedures.”
But, despite all these differences “favoring” PCCs, the surgical hemostasis was identical in practical terms – the difference in blood loss between cohorts was only 12 mL on average, only a handful of patients in each cohort required any sort of transfusion, and the total number of units transfused was nearly identical. In fact, half of the FFP patients never had full INR reversal – with apparently no clinically important consequence. Surgical cases went to the OR much faster with PCCs – so, as above, in an emergent or semi-emergent instance, PCCs are a great option. Absent such a rush, however, ignore this Special Advertising Supplement masquerading as science in a supposedly reputable journal.
“Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial”
http://www.ncbi.nlm.nih.gov/pubmed/25728933