Low-Titer O Positive Whole Blood Versus Component Therapy for Emergent Transfusion in Trauma Patients

Adult male patients brought to the emergency department as Level A trauma activations who are receiving emergency blood transfusion.

Objectives

1. Evaluate PRBC equivalents transfused in each group in the first 24 hours (Primary outcome)
2. Evaluate total transfusion in each group in the first 24 hours (Secondary Outcome) including breakdown by FFP equivalents, platelet units, and cryoprecipitate
3. Evaluate 6 hour, 24 hour, and hospital mortality (Secondary Outcome)
4. Evaluate ICU outcomes in each group

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Hemorrhagic Shock; Acute Blood Loss Anemia
• Intervention / Treatment: Combination product: Routine labs

Detailed Description

Based on the results from Cotton et al, median transfusion in the component therapy group was 6 PRBC in the first 24 hours and 4 PRBC equivalents in the whole blood group. The standard deviation (estimated from the interquartile range) was approximately 4. Thus with an expectation of alpha = 0.05 and expected power of 90% to detect a similar 2 unit difference in transfusion volume, a sample size of 190 should be sufficient; thus projected sample size of 200 should be more than adequate. Age range will be 18 years and older, and only males will be included in the study. Expected racial/ethnic distribution will be approximately 60% white, 15% black, 8% Asian, and 18% other race. No actual recruitment will be performed; rather all qualifying patients will be included. Consent waiver is being requested.

b. Objectives

1. Evaluate PRBC equivalents transfused in each group in the first 24 hours (Primary outcome)
2. Evaluate total transfusion in each group in the first 24 hours (Secondary Outcome) including breakdown by FFP equivalents, platelet units, and cryoprecipitate
3. Evaluate 6 hour, 24 hour, and hospital mortality (Secondary Outcome)
4. Evaluate ICU outcomes in each group:

1. ICU length of stay 2. Ventilator days 3. SOFA score on day of ICU discharge 4. Presence of ARDS 5. Presence of TRALI 6. Presence of DVT/PE 7. Necessity for Dialysis 8. Necessity for Tracheostomy 9. Evaluate viscoelastic testing parameters in both groups when sent on arrival in ICU

1. Percentage of patients with EXTEM clotting time > 80 sec 2. Percentage of patients with EXTEM amplitude at 10 min < 40mm and FIBTEM amplitude at 10 min ≤ 10mm 3. Percentage of patients with EXTEM amplitude at 10 min < 40mm and FIBTEM amplitude at 10 min > 10mm 4. Percentage of patients with maximum thrombolysis > 15% 5. Interval analyses to be performed after 6 and 12 months with provision to continue the study out to 24 months.

1. Stopping rule: A statistically significant difference in hospital mortality at 6 months or 12 months

1. If in favor of LTOWB, consideration of trial termination and making LTOWB the primary standard of care for all trauma patients receiving emergency transfusion except for child-bearing age females (unless Rh immunoglobulin can be administered)
2. If in favor of component therapy, consideration of trial termination and making component therapy the primary standard care for all trauma patients receiving emergency transfusion

• Study Type: Interventional
• Enrollment (Actual): 201
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Anthony M Strada, MD; Phone Number: 603-953-6795; Email: tonymstrada@gmail.com
• Study Contact Backup: Name: Kaushik Mukherjee, MD; Phone Number: 909-558-4877; Email: kmukherjee@llu.edu

Study Locations

• United States
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• all adult male patients brought into the emergency department as LEVEL A trauma activations who are receiving emergency blood transfusions

Exclusion Criteria:

• Female patients (specifically excluded due to risk of alloimmunization of Rh-negative female patients of childbearing age against Rh-positive blood)
• children
• prisoners
• all patients classified as dead upon arrival to the trauma bay

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Titer O+ Whole Blood; Low Titer O+ Whole blood provided to Level A trauma patients	Combination product: Routine labs; Routine labs will be performed with CBC, BMP, Fox screen, ROTEM viscoelastic test, PT/INR, PTT and venous lactate for standard of care for all patients.
Active Comparator: Component Therapy; Component Therapy of O+ pRBC and FFP dispatched to trauma bay for level A traumas	Combination product: Routine labs; Routine labs will be performed with CBC, BMP, Fox screen, ROTEM viscoelastic test, PT/INR, PTT and venous lactate for standard of care for all patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pRBC equivalents transfused	assessment of pRBC equivalents transfused in each arm, an increase in HGB by 1g/dl per unit transfused will be considered successful A blood draw of 5ml will be obtained and tested to assess HGB level. An increase in HGB by 1g/dl per unit transfused will be considered a successful result.	24 hours post ED admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Assessment of mortality This is a composite measurement which includes the following in order to be assessed as pulseless with no respiratory drive or brain death: there is no evidence of arousal or awareness to maximal external stimuli; pupils are fixed in a midsized or dilated position and non reactive to light; corneal, oculocephalic and oculovestibular reflexes are absent; There is no facial movement to noxious stimuli; the gag reflex is absent to bilateral posterior pharyngeal stimuli; the cough reflex is absent to deep tracheal suctioning; there is no brain mediated motor response to noxious stimuli of the limbs; spontaneous respirations are not observed when apnea test targets reach pH <7.30 and PaCO2 >60mmhg	Change between ED admission date and 24 hours post discharge

Collaborators and Investigators

• Sponsor: Loma Linda University

Publications and helpful links

General Publications

• Williams J, Merutka N, Meyer D, Bai Y, Prater S, Cabrera R, Holcomb JB, Wade CE, Love JD, Cotton BA. Safety profile and impact of low-titer group O whole blood for emergency use in trauma. J Trauma Acute Care Surg. 2020 Jan;88(1):87-93. doi: 10.1097/TA.0000000000002498.
• Murphy C, Silva de Leonardi N. The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage. Transfusion. 2021 Apr;61(4):1341-1342. doi: 10.1111/trf.16266. No abstract available.
• Seheult JN, Anto V, Alarcon LH, Sperry JL, Triulzi DJ, Yazer MH. Clinical outcomes among low-titer group O whole blood recipients compared to recipients of conventional components in civilian trauma resuscitation. Transfusion. 2018 Aug;58(8):1838-1845. doi: 10.1111/trf.14779. Epub 2018 Aug 30.
• Hanna K, Bible L, Chehab M, Asmar S, Douglas M, Ditillo M, Castanon L, Tang A, Joseph B. Nationwide analysis of whole blood hemostatic resuscitation in civilian trauma. J Trauma Acute Care Surg. 2020 Aug;89(2):329-335. doi: 10.1097/TA.0000000000002753.
• Cotton BA, Podbielski J, Camp E, Welch T, del Junco D, Bai Y, Hobbs R, Scroggins J, Hartwell B, Kozar RA, Wade CE, Holcomb JB; Early Whole Blood Investigators. A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann Surg. 2013 Oct;258(4):527-32; discussion 532-3. doi: 10.1097/SLA.0b013e3182a4ffa0. Erratum In: Ann Surg. 2014 Jul;260(1):178.

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2022
• Primary Completion (Actual): May 15, 2023
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: June 7, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (Actual): October 18, 2021

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Hemorrhage; Shock; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Brain Injuries, Traumatic; Shock, Hemorrhagic
• Other Study ID Numbers: 5210170

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes