The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

Abstract

Background The Netherlands Armed Forces have been successfully using deep-frozen (− 80 °C) thrombocyte concentrate (DTC) for the treatment of (massive) bleeding trauma patients in austere environments since 2001. However, high-quality evidence for the effectiveness and safety of DTCs is currently lacking. Therefore, the MAssive transfusion of Frozen bloOD (MAFOD) trial is designed to compare the haemostatic effect of DTCs versus room temperature-stored platelets (RSP) in the treatment of surgical bleeding. Methods The MAFOD trial is a single-blinded, randomized controlled non-inferiority trial and will be conducted in three level 1 trauma centres in The Netherlands. Patients 12 years or older, alive at hospital presentation, requiring a massive transfusion including platelets and with signed (deferred) consent will be included. The primary outcome is the percentage of patients that have achieved haemostasis within 6 h and show signs of life. Haemostasis is defined as the time in minutes from arrival to the time of the last blood component transfusion (plasma/platelets or red blood cells), followed by a 2-h transfusion-free period. This is the first randomized controlled study investigating DTCs in trauma and vascular surgical bleeding. Discussion The hypothesis is that the percentage of patients that will achieve haemostasis in the DTC group is at least equal to the RSP group (85%). With a power of 80%, a significance level of 5% and a non-inferiority limit of 15%, a total of 71 patients in each arm are required, thus resulting in a total of 158 patients, including a 10% refusal rate. The data collected during the study could help improve the use of platelets during resuscitation management. If proven non-inferior in civilian settings, frozen platelets may be used in the future to optimize logistics and improve platelet availability in rural or remote areas for the treatment of (massive) bleeding trauma patients in civilian settings. Trial registration ClinicalTrials.gov NCT05502809. Registered on 16 August 2022.

Frozen for combat: Quality of deep‐frozen thrombocytes, produced and used by The Netherlands Armed Forces 2001–2021

“…Up to date all clinical trials conducted with concentrated 5%–6% DMSO frozen platelets used products stored up to 2 years at −80°C 21,24–28 . It remains to be shown if products stored beyond 2 years have equal clinical effects, the MAssive transfusion of Frozen bloOD (MAFOD) clinical trial http://clinicaltrials.gov NCT05502809 may provide this evidence in the future 49,50 …”