1. Prehospital Air Medical Plasma (PAMPer) Trial TACTIC at AAST September 9th

2. Hemorrhage Following Injury

3. Introduction Over 25% of injured patients present with coagulopathy upon arrival to trauma centerOver 25% of injured patients present with coagulopathy upon arrival to trauma center Paying attention to or preventing coagulopathy early post injury improves outcomePaying attention to or preventing coagulopathy early post injury improves outcome Does prehospital plasma improve outcomes?Does prehospital plasma improve outcomes?

4. PAMPer Multi-center, prospective, randomized, open label, interventional trial over 4 years focusing on patients with hemorrhagic shock who are transported via air medical transport to definitive care.

5. AIMs Primary Aim #1: Determine whether prehospital infusion of AB plasma (2 units) as compared to standard air medical care results in a reduction in 30 day mortality : Lower 24 hour blood transfusion volume, lower incidence of MOF, NI, ALI and TRALI.Secondary Aim #1: Lower 24 hour blood transfusion volume, lower incidence of MOF, NI, ALI and TRALI. Secondary Aim #2: Reduction of blood component transfusion and resuscitation requirements over the first 24 hours post-injury. Secondary Aim #3: Improved coagulation measurements (INR, PT/PTT) and TEG parameters. Secondary Aim #4: Lower levels of early IL-6 cytokine expression, reduced thrombomodulin and increased protein C levels.

6. 1. UPMC-Pittsburgh, 2. CWRU MetroHealth-Cleveland, 3. University Louisville, 4. Vanderbilt Univ., Nashville, 5. UTSW- Parkland,Texas, 6. Univ Tennessee, Knoxville PAMPer Trial

7. Randomization Specific air bases at each participating site will be defined before initiation of the trialSpecific air bases at each participating site will be defined before initiation of the trial AB (universal donor) thawed plasma will be carried in a cooler on the air medical transport helicopters for each flight (shelf life 5 days) for one month periodsAB (universal donor) thawed plasma will be carried in a cooler on the air medical transport helicopters for each flight (shelf life 5 days) for one month periods Randomized to plasma or control each monthRandomized to plasma or control each month Unused thawed plasma will be recycled on day 4 by most study sites via courier or at participating blood banksUnused thawed plasma will be recycled on day 4 by most study sites via courier or at participating blood banks Each respective air base will either have plasma on board for the month or be considered a control helicopter for the month with only dummy plasma bagsEach respective air base will either have plasma on board for the month or be considered a control helicopter for the month with only dummy plasma bags

8. Inclusion Criteria #1. Transporting from scene or referral hospital to PAMPer site PAMPer site #2. #2. Systolic blood pressure below 90mmHg and tachycardia > 108 BPM at scene, at the outside hospital with transport team present or during helicopter transport #3. #3. Systolic blood pressure below 70mmHg at scene or at outside hospital with transport team present or during helicopter transport AND OR Requires #1 and #2 or #3

9. Intervention During plasma months: 2 units of AB+ thawed plasma will be initiated en route during air medical transport after inclusion/exclusion criteria are met2 units of AB+ thawed plasma will be initiated en route during air medical transport after inclusion/exclusion criteria are met Full intervention (2 units) will be given with continuation of infusion following arrival if not completedFull intervention (2 units) will be given with continuation of infusion following arrival if not completed

10. Standard Operating Procedures NO Continuation in-hospital resuscitation/care Goal Directed Prehospital resuscitation SOP: Hypotension (SBP< 90))? Trauma Center Arrival Crystalloid Bolus or Blood Transfusion Maintenance crystalloid infusion only YES Receives Intervention or Control

11. Sample Size Power-30 Day Mortality Evidence based mortality estimate 22% 88% power detect 14% difference 22% vs. 8% Cluster Design Adjustment = 1.75 2 interim analyses 265 patients per arm = 530 patients 88% power for possibility of within cluster variation

12. Sampling 1 st Hour 72 Hours +/- 24 Hours r-TEG PT/PTT/INR Serum Protein C IL6 Thrombomodulin TACTIC r-TEG PT/PTT/INR Serum Protein C IL6 Thrombomodulin TACTIC TACTIC

13. Enrollment Enrolled 21 patients 3 Deaths –1 Hemorrhagic shock –1 Brain injury –1 Combined

14. Prelim TEG Data PlasmaControl

15. Questions ??

16. Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial

17. Hemorrhage Following Injury

18. Introduction A recent single non-U.S. study suggests giving Tranexamic Acid (TXA) lowers mortality if given early after arrival to the hospital in patients at risk for bleeding post-injuryA recent single non-U.S. study suggests giving Tranexamic Acid (TXA) lowers mortality if given early after arrival to the hospital in patients at risk for bleeding post-injury TXA is an Anti-fibrinolytic and Hyperfibrinolysis has been shown to be a risk factor for poor outcome and coagulopathy post-injuryTXA is an Anti-fibrinolytic and Hyperfibrinolysis has been shown to be a risk factor for poor outcome and coagulopathy post-injury Whether TXA safely lowers mortality in the US and how TXA lowers mortality post-injury if it does, remains unknownWhether TXA safely lowers mortality in the US and how TXA lowers mortality post-injury if it does, remains unknown Does prehospital TXA improve outcomes and by what mechanism?Does prehospital TXA improve outcomes and by what mechanism?

19. STAAMP Multi-center, prospective, randomized, blinded, controlled interventional trial over 3 years focusing on patients with concern for bleeding who are transported via air medical transport to definitive care.

20. STAAMP Primary Aim#1 : Determine whether prehospital tranexamic acid as compared to placebo results in a lower incidence of 30 day mortalityPrimary Aim#1 : Determine whether prehospital tranexamic acid as compared to placebo results in a lower incidence of 30 day mortality Secondary Aim#1 : Lowers 24 hr motality, ALI, MOF, NI, early resuscitation and transfusion requirements.Secondary Aim#1 : Lowers 24 hr motality, ALI, MOF, NI, early resuscitation and transfusion requirements. Secondary Aim#2 : Reduces hyperfibrinolysis, lowers the incidence of acute traumatic coagulopathy and improves early markers of coagulopathy.Secondary Aim#2 : Reduces hyperfibrinolysis, lowers the incidence of acute traumatic coagulopathy and improves early markers of coagulopathy. Secondary Aim#3 : To explore novel mechanisms by which prehospital TXA alters the inflammatory response independent of effects on hyperfibrinolysis; including analysis of platelet and leukocyte activation, plasmin levels and plasmin mediated complement activation and the early cytokine response to trauma.Secondary Aim#3 : To explore novel mechanisms by which prehospital TXA alters the inflammatory response independent of effects on hyperfibrinolysis; including analysis of platelet and leukocyte activation, plasmin levels and plasmin mediated complement activation and the early cytokine response to trauma. Secondary Aim#4 : Determine whether different dosing regimens of TXA upon arrival in the hospital are associated with improvements in hyperfibrinolysis, coagulopathy, clinical outcomes and the early inflammatory response.Secondary Aim#4 : Determine whether different dosing regimens of TXA upon arrival in the hospital are associated with improvements in hyperfibrinolysis, coagulopathy, clinical outcomes and the early inflammatory response.

21. STAAMP

22. Randomization Specific air bases at each participating site will be defined before initiation of the trialSpecific air bases at each participating site will be defined before initiation of the trial Predefined randomization in double blinded fashion will be prepared by pharmacy at the University Pittsburgh (IDS)Predefined randomization in double blinded fashion will be prepared by pharmacy at the University Pittsburgh (IDS) 10cc of either TXA or sterile placebo will be mixed in provided 100cc saline bag10cc of either TXA or sterile placebo will be mixed in provided 100cc saline bag Only TXA Intervention/Dose # will need to be recorded and provided to hospital research staffOnly TXA Intervention/Dose # will need to be recorded and provided to hospital research staff

23. Inclusion Criteria #1. Transporting from scene or referral hospital to STAAMP site within 2 hours of injury at risk of bleeding STAAMP site within 2 hours of injury at risk of bleeding #2. #2. Systolic blood pressure below 90mmHg: i. At scene of injury or during air medical transport ii. Documented at referring hospital prior to air medical transport arrival #3. #3. Tachycardia > 110 beats per minute: i. At scene of injury or during air medical transport ii. Documented at referring hospital prior to air medical transport arrival AND OR Requires #1 and #2 or #3

24. Intervention Tranexamic Acid (TXA): Prehospital Intervention 1 gm of TXA or placebo, in double blinded fashion, will be initiated en route during air medical transport after inclusion/exclusion criteria are met1 gm of TXA or placebo, in double blinded fashion, will be initiated en route during air medical transport after inclusion/exclusion criteria are met

25. Intervention Tranexamic Acid (TXA): In-Hospital Intervention

26. Sample Size Power-30 Day Mortality Evidence based mortality estimate 16% 90% power to detect 7% difference 9% vs. 16% 80% power to detect 6% difference 10% vs. 16% 2 interim analyses 497 patients per arm = 994 patients

27. Sampling 1 st Hour 72 Hours 24 Hours r-TEG PT/PTT/INR Serum Ddimer Protein C Plasmin- Antiplasmin ComplementCyto kine HMGB1 TACTIC Whole Blood Platelet/Leukocyte Activation Gene Expression 12 Hours r-TEG PT/PTT/INR Serum Ddimer Protein C Plasmin- Antiplasmin ComplementCyto kine HMGB1 TACTIC Whole Blood Platelet/Leukocyte Activation Gene Expression r-TEG PT/PTT/INR Serum Ddimer Protein C Plasmin- Antiplasmin ComplementCyto kine HMGB1 TACTIC Whole Blood Platelet/Leukocyte Activation Gene Expression Serum Ddimer Protein C Plasmin- Antiplasmin ComplementCyto kine HMGB1 TACTIC

28. Questions ??