Pre-Hospital Use of Plasma for Traumatic Hemorrhage (PUPTH)

Type A Thawed Plasma (TP) will be compared in polytrauma patients who receive only Normal Saline (NS) (standard of care) before arrival at the hospital.

The purpose of this study is to determine if prehospital administration of thawed plasma can reduce mortality of patients who have lost a large amount of blood due to their injuries, compared to those receiving standard of care.

Study Overview

• Status: Withdrawn
• Conditions: Shock, Hemorrhagic
• Intervention / Treatment: Biological: Plasma; Drug: Normal saline

Detailed Description

INVESTIGATIONAL PLAN This will be an open-label, non-blinded, randomized clinical trial to investigate mortality (30 days) and morbidity of Type A thawed Plasma (TP) versus NS infusion at earliest contact, administered by Emergency Medical Service (EMS) supervisors to subjects who have sustained severe Polytrauma / Major hemorrhage (PTr / MH). The total study is expected to last 2 years with 210 patients enrolled.

The two EMS agencies involved in the study will each have one EMS supervisor quick-response vehicle (QRV) equipped with an approved, validated refrigeration unit for TP transport. EMS personnel trained in plasma administration and recognition of reactions may administer up to 2 units of TP to subjects approved for study enrollment. Blood samples for coagulation and lipid testing will be drawn prior to TP administration by EMS personnel,and repeated by hospital personnel at 30 minutes, 8 hours, and 24 hours post-injury.

This study is approved for "Exception from Informed Consent" (EFIC). Once the patient has reached VCUMC and has been entered into the VCUMC health care system, the treating team will advise the Study Coordinator (SC) whether or not a subject is able to consent. As the plasma administration will occur in the field prior to arrival to VCUMC, the SC will make every effort possible to obtain consent from the subject or legally authorized representative (LAR) for continued study participation before the next intervention (8 hour blood specimen collection). The attempts to contact the LAR will be documented in detail. If a subject lacks the ability to provide his/her own consent by the end of day 30, the consent signed by the LAR will be the consent document in force at the subject's completion of the study and no further consent will be sought.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Blunt or penetrating trauma,
• Blood Pressure (BP) systolic <70 mmHg or BP 70-90 mmHg with Heart Rate (HR) > 108 Beats Per Minute (BPM),
• Ongoing hemorrhage with unstable vital signs

Exclusion Criteria:

• Wearing opt-out wrist band,
• Wearing medical alert jewelry / bracelet, etc. indicating Jehovah Witness or similar with objections to blood transfusions,
• Refusal to participate (by subject or LAR),
• Communication barrier at the time of eliciting refusal (non-English speaking or non-Spanish speaking),
• Not expected to survive transport to Virginia Commonwealth University Medical Center (VCUMC),
• Documented Do Not Resuscitate (DNR) order found,
• Cardiac arrest or Cardio-Pulmonary Resuscitation (CPR) prior to randomization
• Penetrating head trauma,
• Known / obvious pregnancy,
• Prisoner,
• Burns > 20% of body surface

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Type A Thawed Plasma; Eligible subjects with polytrauma (PT) and major hemorrhage (MH) will be randomized to receive 2 units of thawed Type A plasma in the pre-hospital setting administered by EMS first responders. An exception from informed consent under 21CFR 50.24 is required since enrollment will occur (for the majority of subjects) before consent can be obtained.	Biological: Plasma; Type A thawed plasma (up to 2 units) will be administered to polytrauma subjects randomized to plasma arm of study; Other Names: Thawed Plasma
Placebo Comparator: Normal saline; Eligible subjects with polytrauma (PT) and major hemorrhage (MH) will be randomized to receive normal saline in the pre-hospital setting administered by EMS first responders. Normal saline is standard of care	Drug: Normal saline; Normal saline will be administered to polytrauma subjects randomized to normal saline arm of study; Other Names: 0.9% Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	all cause mortality	30 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coagulation function (thromboelastography, RoTEM, Hemodyne, fibrinogen, D-dimer, PFA-100, platelet count, flow cytometry)	thromboelastography, RoTEM, Hemodyne, fibrinogen, D-dimer, PFA-100, platelet count, flow cytometry	24 hours
Vital signs (blood pressure, pulse, temperature)	blood pressure, pulse, temperature	24 hours
Blood product utilization (number of red blood cell units, number of plasma units, number of platelet units cryoprecipitate doses)	number of red blood cell units, number of plasma units, number of platelet units cryoprecipitate doses	30 days
Lipidomic profiles (arachidonic acid, eicosinoid expression, prostacyclin expression)	arachidonic acid, eicosinoid expression, prostacyclin expression	24 hours
Blood biochemistry (pH, bicarbonate, lactate)	pH, bicarbonate, lactate	24 hours
Hematology (Hemoglobin, hematocrit)	Hemoglobin, hematocrit	24 hours
Hospital outcomes (number of cases of multi-system organ failure (MSOF), renal failure, length of hospital stay, length of ICU stay, number of days on a ventilator, number of surgeries, number of infections)	number of cases of multi-system organ failure (MSOF), renal failure, length of hospital stay, length of ICU stay, number of days on a ventilator, number of surgeries, number of infections	30 days

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: United States Department of Defense
• Investigators: Principal Investigator: Bruce D Spiess, MD, FAHA, VCU

Publications and helpful links

General Publications

• 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.
• Reynolds PS, Michael MJ, Spiess BD. Application of Incident Command Structure to clinical trial management in the academic setting: principles and lessons learned. Trials. 2017 Feb 9;18(1):62. doi: 10.1186/s13063-016-1755-9.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 6, 2014
• First Submitted That Met QC Criteria: November 28, 2014
• First Posted (Estimate): December 1, 2014

Study Record Updates

• Last Update Posted (Estimate): February 23, 2016
• Last Update Submitted That Met QC Criteria: February 19, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Shock; Trauma; Hemorrhage; Plasma; Polytrauma
• Additional Relevant MeSH Terms: Pathologic Processes; Shock; Hemorrhage; Shock, Hemorrhagic
• Other Study ID Numbers: HM14813; IND #15910 (Registry Identifier: FDA); W81XWH-12-2-0022 (Other Grant/Funding Number: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no data to share.