Control of Major Bleeding After Trauma Study

Trauma Clinical Trial

— COMBAT  

Official title:

A Prospective, Randomized Comparison of Fresh Frozen Plasma Versus Standard Crystalloid Intravenous Fluid as Initial Resuscitation Fluid

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01838863
• Other study ID #: COMIRB# 12-1349
• Secondary ID: W81XWH1220028
• Status: Terminated
• Phase: Phase 2
• Start date: April 7, 2014
• Est. completion date: April 3, 2017

Study information

• Verified date: December 2018
• Source: Denver Health and Hospital Authority
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 144
• Est. completion date: April 3, 2017
• Est. primary completion date: April 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhagic Shock
• Shock, Hemorrhagic
• Trauma

Intervention

Biological:
• Type AB plasma
The plasma is thawed and administered to subjects in the experimental (plasma) arm.

Drug:
• Crystalloid fluid (standard of care for resuscitation)
Normal saline will be give to subjects in the standard arm as the current standard of care for an initial resuscitation fluid

Locations

Country	Name	City	State
United States	Denver Health Medical Center	Denver	Colorado

Sponsors (3)

Lead Sponsor	Collaborator
Denver Health and Hospital Authority	U.S. Army Medical Research and Materiel Command, University of Colorado, Denver

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Baseline (Field) Coagulation Factor Levels	defined as the first coagulation factor level obtained in the field prior to intervention; Coagulation Factor Reference Ranges; F2 F5 F7 F8 F9 F11; % % % % % % 67.0 - 107.0 63.0 - 116.0 52.0 - 120.0 58.0 - 132.0 47.0 - 122.0 52.0 - 120.0	after injury and prior to hospital arrival, at about 15 minutes after injury
Other	Number of Participants With Abnormal Baseline (Field) Coagulation Factor XIII Level	defined as abnormal coagulation factor XIII level obtained in the field prior to intervention	after injury prior to hospital arrival
Other	Admission (First Arrival) Coagulation Factor Levels	defined as the first coagulation factor level obtained upon ED arrival; Coagulation Factor Reference Ranges; F2 F5 F7 F8 F9 F11; % % % % % % 67.0 - 107.0 63.0 - 116.0 52.0 - 120.0 58.0 - 132.0 47.0 - 122.0 52.0 - 120.0	after injury prior to hospital arrival
Other	Number of Participants With Abnormal Admission Coagulation Factor XIII (Fibrin-stabilizing Factor) Level	defined as the first abnormal factor XIII (fibrin-stabilizing factor) level obtained upon ED arrival	within 30 minutes of Emergency Department (ED) arrival
Other	Exploratory Analyses	Number of participants with 24-hour mortality, adverse outcome free days and transfusions	Hospital stay up to 28 days.
Other	Exploratory Analyses.	Adverse outcome free days	Hospital stay up to 28 days.
Other	Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in the Sub-group With Less Severe Hemorrhagic Shock	Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater	Hospital stay up to 28 days.
Other	Adverse Outcome-free Days in a Sub-group With Less Severe Hemorrhagic Shock	Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater	Hospital stay up to 28 days.
Other	Level of Haemoglobin (Hb) in a Sub-group With Less Severe Hemorrhagic Shock	Level of Haemoglobin (Hb) in g/dL in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater	Hospital stay up to 28 days.
Other	Blood Product Transfusion in a Sub-group With Less Severe Hemorrhagic Shock	Transfusions of blood products in units in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater	Hospital stay up to 28 days.
Other	Time to Admission and First Blood Transfusion in a Sub-group With Less Severe Hemorrhagic Shock	Time to Admission and First Blood Transfusion in minutes in the patients with initial systolic blood pressure (SBP) 71-90 mmHg and heart rate (HR) of 108 or greater	Hospital stay up to 28 days.
Other	Number of Participants With Mortality, Adverse Outcome-free Days and Transfusions in a Sub-group With Severe Hemorrhagic Shock	Mortality, adverse outcome-free days and transfusions in the patients with initial systolic blood pressure (SBP) <=70 mmHg	Hospital stay up to 28 days.
Other	Number of Adverse Outcome Free Days in a Sub-group With Severe Hemorrhagic Shock	Adverse outcome-free days in the patients with initial systolic blood pressure (SBP) <=70 mmHg	Hospital stay up to 28 days.
Other	Number of Participants in a Sub-group With no Severe Traumatic Brain Injury (TBI)	Number of participants with mortality, adverse outcome-free days and transfusions in the patients with no severe traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3.	Hospital stay up to 28 days.
Other	Exploratory Analyses in a Sub-group With Severe Traumatic Brain Injury (TBI)	Number of participants with 28-day mortality. Traumatic brain injury (TBI) is defined as Abbreviated Injury Score (AIS) for Head/Neck >=3.	Hospital stay up to 28 days.
Other	Severe Adverse Events (SAE)	Number of participants with severe adverse events (SAE)	Hospital stay up to day 28
Other	Haemoglobin (Hb) Level in a Sub-group With Severe Hemorrhagic Shock	Haemoglobin (Hb) level in the patients with initial systolic blood pressure (SBP) <=70 mmHg	Hospital stay up to 28 days.
Other	Blood Product Transfusion in a Sub-group With Severe Hemorrhagic Shock	Number of blood products transfused in units in the patients with initial systolic blood pressure (SBP) <=70 mmHg	Hospital stay up to 28 days.
Other	Time to Admission and First Blood Transfusion in a Sub-group With Severe Hemorrhagic Shock	Time to Admission and First Blood Transfusion in the patients with initial systolic blood pressure (SBP) <=70 mmHg	Hospital stay up to 28 days.
Other	Haemoglobin (Hb) Level	Haemoglobin (Hb) level in g/dL units.	Hospital stay up to 28 days.
Other	Number of Blood Products Transfused.	Number of blood products transfused in units.	Hospital stay up to 28 days.
Other	Time to Admission and First Blood Transfusion	Time to admission and first blood product transfusion in minutes.	Hospital stay up to 28 days.
Primary	Number of Participants That Died Within 28 Days Post Injury	death within 28 days post injury (death of any cause except for death due to a second, clearly unrelated traumatic injury suffered after discharge)	28 days
Secondary	Composite Outcome of 28-day In-hospital Mortality and Postinjury Multiple Organ Failure (MOF) Incidence	The occurrence of in-hospital death or MOF within the first 28 days postinjury. MOF is defined using the validated Denver MOF score (Denver MOF score>3 of simultaneously obtained scores after 48 hours postinjury).	28 days
Secondary	Admission Coagulopathy	Defined as the first international normalized ratio (INR) obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot.	within 30 minutes of Emergency Department (ED) arrival
Secondary	Number of Participants With Admission Severe Coagulopathy	Defined as international normalized ratio (INR) >1.3 obtained upon ED arrival. The international normalized ratio (INR) is an international standard for the prothrombin time (PT). This measures the time it takes for blood to clot. The normal range for a healthy person is 0.83-1.19. Usually, a high INR indicates a higher risk of bleeding, while a low INR suggests a higher risk of developing a clot.	within 30 minutes of Emergency Department (ED) arrival
Secondary	Admission Clot Strength	Admission clot strength will be measured by thrombelastography G-value upon ED arrival. Clot strength measured in kilodynes per square centimetre (kdyn/cm^2).	within 30 minutes of ED arrival
Secondary	Admission Acidosis	Admission acidosis measured by lactate upon ED arrival.	within 30 minutes of ED arrival
Secondary	Number of Participants With Admission Severe Acidosis	Admission severe acidosis measured by lactate>5 upon ED arrival.	within 30 minutes of ED arrival
Secondary	Admission Acidosis	Admission acidosis will be defined by base deficit (BD) upon ED arrival.	within 30 minutes of ED arrival
Secondary	Number of Participants With Admission Severe Acidosis	Admission severe acidosis will be defined by base deficit (BD>10) upon ED arrival.	within 30 minutes of ED arrival