PreHospital Air Medical Plasma Trial (PAMPer)

Prehospital Air Medical Plasma (PAMPer) Phase III Multicenter, Prospective, Randomized, Open-label, Interventional Trial A Four Year Multicenter Open Label Randomized Trial

To determine the effect of the prehospital infusion during air transport of 2 units of AB plasma on 30 day mortality in patients with hemorrhagic shock as compared to conventional care.

Study Overview

• Status: Completed
• Conditions: Hemmorhagic Shock During Air Medical Transport
• Intervention / Treatment: Biological: infusion of 2 units of plasma

Detailed Description

Background: Although advances in the care of the severely injured patient have occurred over the last decade, patients continue to be plagued with uncontrolled hemorrhage resulting in significant early mortality and the development of multiple organ failure and associated complications. A primary driving force for this unbridled hemorrhage has been shown to be the early coagulopathy which complicates severe injury. Increasing evidence suggests that blood component transfusion protocols that address this early coagulopathy, once a patient arrives at a trauma center, are associated with lower mortality and a reduction in blood component transfusion requirements. Prehospital interventions which quell this early coagulopathy in an earlier setting have the potential to minimize or even prevent this vicious hemorrhagic cascade, further lowering blood component transfusion requirements and reducing the resultant morbid sequelae which complicates severe injury.

Objective/Hypothesis: The primary hypothesis will be that prehospital infusion of plasma during air medical transport in patients with hemorrhagic shock will lower 30 day mortality. The secondary hypotheses include that prehospital infusion of plasma will reduce 24 hour blood transfusion, multiple organ failure, nosocomial infection, and acute lung injury, reduce or prevent the early coagulopathy as demonstrated by improving presenting coagulation and thromboelastography parameters, and reduce the early inflammatory cytokine response, thrombomodulin and increase protein C levels.

• Study Type: Interventional
• Enrollment (Actual): 523
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: Hemorrhagic shock not responsive to crystalloid infusion -

Exclusion Criteria: Isolated Fall, Cervical cord injury, prisoner, pregnant patient, traumatic arrest

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: plasma; infusion of 2 units of plasma	Biological: infusion of 2 units of plasma; infusion of 2 units of plasma
No Intervention: standard air medical care; control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Our Primary Outcome for the Proposal Will be 30 Day Mortality	All cause 30 day mortality using imputation for those with missing 30 day mortality.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Twenty Four-Hour Blood Transfusion Requirements	24-hour blood transfusion requirements will be determined by recording blood volume (mls) and number of Units transfused from the time of trauma bay arrival or upon completion of pre-hospital initiated plasma infusion. For survival bias analysis, volumes and number of blood transfusion Units received at 3, 6, 12, and 18 hours will also be recorded.	at twenty four hours
In-hospital Mortality	In hospital mortality will be prospectively recorded from the time of trauma bay arrival. Over the first 24 hours we will document and record the time of death in hours, while after the 24 hour time point, we will document and record the time of death in days from arrival. We suspect that patients in hemorrhagic shock will have a significant percentage of mortality occurring in the first 24 hour period.	during hospitalization
Multiple Organ Failure	Organ dysfunction will be evaluated via a well-validated scoring system referred to as the Multiple Organ Dysfunction Score (MODScore). Patients who are never admitted to the ICU or those with a length of ICU stay of less than 48 hours will be considered to have a MODScore of 0. A summary of the MODScore may be calculated by summing the worst scores of each of the individual systems over the course of the ICU stay (Table 1). A summary MODScore > 5 will be classified as multiple organ failure (MOF). Scores will be determined daily up until post injury day 28 or ICU discharge.	during hospitalization
Acute Lung Injury (ALI) and Transfusion Related Acute Lung Injury (TRALI)	Development of ALI will be assessed which includes: 1) bilateral infiltrates on chest x-ray, 2) a capillary wedge pressure < 18mmHg, and 3) Pao2/Fio2 ratio < 300 via blood gas analysis. In those patients without a Swan-Ganz catheter to determine capillary wedge pressure, the absence of signs of, or clinical concern, for elevated left sided atrial pressures will be used for the diagnosis. All patients who remain intubated beyond the first 24 hours post-injury will be evaluated using blood gas analysis and chest x-ray evaluation. Those patients who remain intubated at 48 hours through 7 days will be reevaluated for this outcome at these time points. The diagnosis of TRALI will be defined as when ALI occurs within the first 6 hours from arrival at the trauma center as it is clinically defined.	hospitalization

Collaborators and Investigators

• Sponsor: Jason Sperry
• Collaborators: Vanderbilt University; University of Texas; Case Western Reserve University; University of Louisville; The Methodist Hospital Research Institute; The University of Tennessee, Knoxville; JPS Health Network
• Investigators: Principal Investigator: Jason L Sperry, MD,MPH, University of Pittsburgh

Publications and helpful links

General Publications

• Wu J, Moheimani H, Li S, Kar UK, Bonaroti J, Miller RS, Daley BJ, Harbrecht BG, Claridge JA, Gruen DS, Phelan HA, Guyette FX, Neal MD, Das J, Sperry JL, Billiar TR. High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI. Ann Surg. 2022 Oct 1;276(4):673-683. doi: 10.1097/SLA.0000000000005610. Epub 2022 Jul 19.
• Gruen DS, Guyette FX, Brown JB, Okonkwo DO, Puccio AM, Campwala IK, Tessmer MT, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Neal MD, Zuckerbraun BS, Yazer MH, Billiar TR, Sperry JL. Association of Prehospital Plasma With Survival in Patients With Traumatic Brain Injury: A Secondary Analysis of the PAMPer Cluster Randomized Clinical Trial. JAMA Netw Open. 2020 Oct 1;3(10):e2016869. doi: 10.1001/jamanetworkopen.2020.16869.
• Gruen DS, Brown JB, Guyette FX, Vodovotz Y, Johansson PI, Stensballe J, Barclay DA, Yin J, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Neal MD, Zuckerbraun BS, Billiar TR, Sperry JL; PAMPer study group. Prehospital plasma is associated with distinct biomarker expression following injury. JCI Insight. 2020 Apr 23;5(8):e135350. doi: 10.1172/jci.insight.135350.
• Pusateri AE, Moore EE, Moore HB, Le TD, Guyette FX, Chapman MP, Sauaia A, Ghasabyan A, Chandler J, McVaney K, Brown JB, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putnam AT, Sperry JL. Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes: A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials. JAMA Surg. 2020 Feb 1;155(2):e195085. doi: 10.1001/jamasurg.2019.5085. Epub 2020 Feb 19.
• Sperry JL, Guyette FX, Brown JB, Yazer MH, Triulzi DJ, Early-Young BJ, Adams PW, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putnam AT, Duane TM, Alarcon LH, Callaway CW, Zuckerbraun BS, Neal MD, Rosengart MR, Forsythe RM, Billiar TR, Yealy DM, Peitzman AB, Zenati MS; PAMPer Study Group. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med. 2018 Jul 26;379(4):315-326. doi: 10.1056/NEJMoa1802345.
• Reynolds PS, Michael MJ, Cochran ED, Wegelin JA, Spiess BD. Prehospital use of plasma in traumatic hemorrhage (The PUPTH Trial): study protocol for a randomised controlled trial. Trials. 2015 Jul 30;16:321. doi: 10.1186/s13063-015-0844-5.

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 21, 2013
• First Posted (Estimate): March 26, 2013

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 6, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: hemmorhagic shock, plasma, air medical transport, randomized, multicenter
• Additional Relevant MeSH Terms: Pathologic Processes; Shock
• Other Study ID Numbers: 11152002 IND 15117