Background
Phase 3, multicenter, randomized pragmatic trial (PROPPR). 680 severely injured adult trauma patients at 12 level-1 North American trauma centers, predicted to require massive transfusion (activation of massive transfusion protocol). Patients with penetrating and blunt trauma enrolled; survival to intervention required.
Interventions and follow up
Arm A: Plasma:Platelets:RBC ratio 1:1:1 (one unit plasma and one unit apheresis platelets per unit packed RBC)
Arm B: Plasma:Platelets:RBC ratio 1:1:2 (one unit plasma and one unit apheresis platelets per 2 units packed RBC)
Primary endpoint: 24-hour and 30-day all-cause mortality
mFollow up: 30 day
Arm B: Plasma:Platelets:RBC ratio 1:1:2 (one unit plasma and one unit apheresis platelets per 2 units packed RBC)
Primary endpoint: 24-hour and 30-day all-cause mortality
mFollow up: 30 day
Results
24-hour mortality: 12.7% vs 17.0%, P=.12 — NS
30-day mortality: 22.4% vs 26.1%, P=.26 — NS
Hemostasis achieved: 86% vs 78%, P=.006 — significantly higher with 1:1:1
Death from hemorrhage at 24 hours: 9.2% vs 14.6%, P=.03 — significant reduction
Time to hemorrhage control: No significant difference
30-day mortality: 22.4% vs 26.1%, P=.26 — NS
Hemostasis achieved: 86% vs 78%, P=.006 — significantly higher with 1:1:1
Death from hemorrhage at 24 hours: 9.2% vs 14.6%, P=.03 — significant reduction
Time to hemorrhage control: No significant difference
Adverse events
Main adverse events: ARDS: 26% vs 28% — NS. TRALI: 4% vs 3% — NS. TACO: 8% vs 6% — NS. Sepsis, MOF similar. No significant increase in plasma-related complications with 1:1:1 ratio.
Conclusions
The 1:1:1 ratio did not significantly improve 24-hour or 30-day survival compared to 1:1:2, but significantly improved hemostasis and reduced early hemorrhagic death, supporting higher plasma:platelet ratios in trauma massive transfusion protocols.
Key Limitations
Key Limitations: Trial was underpowered for the primary mortality endpoint — the study was designed to detect a 10-percentage-point difference. The 30-day mortality difference (3.7%) favored 1:1:1 but was not statistically significant. Crossover contamination possible in pragmatic design. Patients surviving to enrollment may represent a survival bias subset. Ratio adherence was not perfect in real-time delivery.
Clinical Context
PROPPR shifted massive transfusion protocols at most major trauma centers toward 1:1:1 ratios, based on the hemostasis and early hemorrhagic death benefit even without significant overall mortality improvement. Current ATLS and trauma guidelines now recommend balanced resuscitation with high plasma:platelet:RBC ratios. PROPPR is the definitive RCT for damage control resuscitation strategy.
References
References: Holcomb JB et al, JAMA 2015 (PROPPR primary)