Prehospital Air Medical Plasma (PAMPer) Trial

TACTIC at AASTSeptember 9th

Hemorrhage Following Injury

Introduction• Over 25% of injured patients present with

coagulopathy upon arrival to trauma center

• Paying attention to or preventing coagulopathy early post injury improves outcome

• Does prehospital plasma improve outcomes?

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.

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

• 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.

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

6. Univ Tennessee, Knoxville

PAMPer Trial

Randomization• Specific 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 periods

• Randomized 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 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 bags

Inclusion Criteria

#1. Transporting from scene or referral hospital to PAMPer site

#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. 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

Intervention

During plasma months:

• 2 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 completed

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

Sample SizePower-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

Sampling

1st Hour

72 Hours

+/- 24 Hours

r-TEG

PT/PTT/INR

SerumProtein C

IL6Thrombomodulin

TACTIC

r-TEG

PT/PTT/INR

SerumProtein C

IL6Thrombomodulin

TACTIC

TACTIC

Enrollment

• Enrolled 21 patients

• 3 Deaths

– 1 Hemorrhagic shock– 1 Brain injury– 1 Combined

Prelim TEG Data

Plasma Control

Questions

??

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

Hemorrhage Following Injury

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-injury

• TXA 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 unknown

• Does prehospital TXA improve outcomes and by what mechanism?

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.

STAAMP

• Primary 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#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#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.

STAAMP

Randomization• Specific 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)

• 10cc 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 staff

Inclusion Criteria

#1. Transporting from scene or referral hospital to STAAMP site within 2 hours of injury at risk of bleeding

#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. 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

InterventionTranexamic 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 met

InterventionTranexamic Acid (TXA):

In-Hospital Intervention

Sample SizePower-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

Sampling

1st Hour

72 Hours

24 Hours

r-TEG

PT/PTT/INR

SerumDdimer

Protein CPlasmin-

AntiplasminComplementCyto

kineHMGB1

TACTIC

Whole BloodPlatelet/Leukocyte

ActivationGene Expression

12 Hours

r-TEG

PT/PTT/INR

SerumDdimer

Protein CPlasmin-

AntiplasminComplementCyto

kineHMGB1

TACTIC

Whole BloodPlatelet/Leukocyte

ActivationGene Expression

r-TEG

PT/PTT/INR

SerumDdimer

Protein CPlasmin-

AntiplasminComplementCyto

kineHMGB1

TACTIC

Whole BloodPlatelet/Leukocyte

ActivationGene Expression

SerumDdimer

Protein CPlasmin-

AntiplasminComplementCyto

kineHMGB1

TACTIC

Questions

??