Clinical trial NCT01838863: Control of Major Bleeding After Trauma Study
Official title: A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Trauma
Hemorrhagic Shock
Keywords: coagulopathy
hemorrhagic shock
plasma
blood product transfusion
Lead sponsor: Denver Health and Hospital Authority
Sponsor class: OTHER
Collaborators: name: U.S. Army Medical Research and Development Command
name: University of Colorado, Denver
First posted: 2013-04-24
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Bleeding is the most avoidable cause of death in trauma patients. Up to one-third of severely injured trauma patients are found to be coagulopathic and forty percent of the mortality following severe injury is due to uncontrollable hemorrhage in the setting of coagulopathy. It has been established that early administration of fresh frozen plasma decreases mortality following severe injury, replacing lost coagulation factors, improving the coagulopathy and restoring blood volume. This study will determine if giving plasma to severely injured trauma patients during ambulance transport versus after arrival to the hospital will help reduce hemorrhage, thus decreasing both total blood product administration and mortality.

Detailed description: Study Design: Severely injured trauma patients with a systolic blood pressure (SBP) ≤ 70 or SBP ≤ 90 with a heart rate ≥ 108 bpm at the scene will be enrolled and randomized to receive either 2 units of frozen plasma thawed in the field or normal saline (the current standard of care), as the initial resuscitation fluid. After this initial resuscitation fluid, both groups will receive the same standard of care, including packed red blood cells, additional normal saline, or plasma as needed based on laboratory and clinical evidence of coagulopathy. Blood samples and clinical information will be collected throughout the hospital stay up to 28 days after injury.

Eligibility criteria: Inclusion Criteria:

* Age\>=18 years
* Acutely injured
* SBP\<70 mmHg or SBP 71-90 mmHg with heart rate (HR)\>108 beats per minute.

Exclusion Criteria:

* Visibly or verbally reported pregnant women
* known prisoners
* unsalvageable injuries (defined as asystolic or cardiopulmonary resuscitation prior to randomization)
* known objection to blood products
* the patient has an opt-out bracelet or, necklace or wallet card
* a family member present at the scene objects to the patient's enrollment in research.

Primary outcomes:
measure: Number of Participants That Died Within 28 Days Post Injury
timeFrame: 28 days
Secondary outcomes:
measure: Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence
timeFrame: 28 days
measure: Admission Coagulopathy
timeFrame: within 30 minutes of Emergency Department (ED) arrival
measure: Number of Participants With Admission Severe Coagulopathy
timeFrame: within 30 minutes of Emergency Department (ED) arrival
measure: Admission Clot Strength
timeFrame: within 30 minutes of ED arrival
measure: Admission Acidosis
timeFrame: within 30 minutes of ED arrival
measure: Number of Participants With Admission Severe Acidosis
timeFrame: within 30 minutes of ED arrival
measure: Admission Acidosis
timeFrame: within 30 minutes of ED arrival
measure: Number of Participants With Admission Severe Acidosis
timeFrame: within 30 minutes of ED arrival
Other outcomes:
measure: Baseline (Field) Coagulation Factor Levels
timeFrame: after injury and prior to hospital arrival, at about 15 minutes after injury
measure: Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level
timeFrame: after injury prior to hospital arrival
measure: Admission (First Arrival) Coagulation Factor Levels
timeFrame: after injury prior to hospital arrival
measure: Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level
timeFrame: within 30 minutes of Emergency Department (ED) arrival
measure: Exploratory Analyses
timeFrame: Hospital stay up to 28 days.
measure: Exploratory Analyses.
timeFrame: Hospital stay up to 28 days.
measure: Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in the Sub-group With Less Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in a Sub-group With Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI)
timeFrame: Hospital stay up to 28 days.
measure: Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI)
timeFrame: Hospital stay up to 28 days.
measure: Severe Adverse Events (SAE)
timeFrame: Hospital stay up to day 28
measure: Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock
timeFrame: Hospital stay up to 28 days.
measure: Haemoglobin (Hb) Level
timeFrame: Hospital stay up to 28 days.
measure: Number of Blood Products Transfused.
timeFrame: Hospital stay up to 28 days.
measure: Time to Admission and First Blood Transfusion
timeFrame: Hospital stay up to 28 days.
Locations:
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
Study officials:
affiliation: Denver Health Medical Center
name: Ernest E Moore, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Moore HB, Moore EE, Chapman MP, McVaney K, Bryskiewicz G, Blechar R, Chin T, Burlew CC, Pieracci F, West FB, Fleming CD, Ghasabyan A, Chandler J, Silliman CC, Banerjee A, Sauaia A. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet. 2018 Jul 28;392(10144):283-291. doi: 10.1016/S0140-6736(18)31553-8. Epub 2018 Jul 20.
citation: 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.
citation: Chapman MP, Moore EE, Chin TL, Ghasabyan A, Chandler J, Stringham J, Gonzalez E, Moore HB, Banerjee A, Silliman CC, Sauaia A. Combat: Initial Experience with a Randomized Clinical Trial of Plasma-Based Resuscitation in the Field for Traumatic Hemorrhagic Shock. Shock. 2015 Aug;44 Suppl 1(0 1):63-70. doi: 10.1097/SHK.0000000000000376.