Whole Blood in Trauma Patients With Hemorrhagic Shock

Trauma Clinical Trial

— WEBSTER  

Official title:

Whole Blood vs. Blood Components Therapy in the Hemostatic Resuscitation of Severe Trauma Patients: An Open-label, Randomized, Controlled Clinical Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05634109
• Other study ID #: 1938
• Status: Recruiting
• Phase: Phase 3
• Start date: January 14, 2023
• Est. completion date: January 2025

Study information

• Verified date: January 2023
• Source: Fundacion Clinica Valle del Lili
• Contact: Alberto F Garcia, MD MSc
• Phone: +576023319090
• Email: alberto.garcia[@]fvl.org.co
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study aims to evaluate among trauma patients with hemorrhagic shock the clinical impact of hemostatic resuscitation between whole blood vs. blood components therapy in the following outcomes in a hierarchical analysis: mortality at 28 days and evolution of organ dysfunction.

Description:

Background: Hemostatic resuscitation is a mainstay in the management of trauma patients. Factors such as blood loss and tissue injury contribute to coagulation and hemodynamic status imbalances. Hemorrhage remains a leading cause of death in trauma patients, despite advances in strategies such as damage control surgery, massive transfusion protocol, and intensive care.

Conventional therapy for hemostatic resuscitation is a blood transfusion seeking a 1:1:1 ratio of red blood cells, plasma, and platelets. However, this ratio has disadvantages in clinical practice, especially in low-resource settings. Whole blood transfusion can contribute to maintaining a physiological rate of cells, clotting factors, and hemostatic properties. Advances in the whole blood elucidated a new opportunity for its implementation in civilian trauma centers. However, the effect of initial resuscitation with whole blood in trauma patients is unclear. This study aims to determine the effect of hemostatic resuscitation using whole blood on mortality and evolution of organ dysfunction in severe trauma patients compared to blood components therapy. This clinical trial attempts to resolve the debate and uncertainty of using whole blood vs. blood components.

Study Design: An open-label, randomized, prospective, single-center and controlled trial will be performed. This study will be included prospectively randomized severe trauma patients who require a blood transfusion. Randomization can assign participants to the experimental arm, transfusing them with 3 units of whole blood. If the participant continues requiring transfusions, the second intervention of 3 units of whole blood can be administered. On the contrary, the randomization can assign to the control arm, where the participant will receive 3 red blood cell units, 3 fresh frozen plasma units, and half of a platelets apheresis, equivalent to 3 platelets units. If required, a second intervention with the same ratio can be transfused to participants.

The primary outcome is a hierarchical composite outcome based on mortality at 28 days and the evolution of organ dysfunction. Organ dysfunction will be measured as the difference in the score between the fifth and first days of the SOFA (Sequential Organ Failure Assessment). Secondary outcomes are mortality, coagulopathy profile, intensive care unit free days, length of hospital stay free days, and volumes of transfusion requirements. Safety outcomes are complications related to transfusion (anaphylaxis, acute hemolytic reaction, acute lung injury) and complications related to trauma patients (acute distress respiratory syndrome, pulmonary embolism, deep vein thrombosis, acute kidney injury with or without dialysis, stroke, myocardial infarction, cardiac arrest, sepsis, abdominal complications, abdominal compartment syndrome)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: January 2025
• Est. primary completion date: February 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (> 18 years)

• Activating institutional trauma code for trauma patients with hemorrhagic shock.

• Candidate for massive transfusion (Patient with an Assessment Blood Consumption (ABC) Score = 2 or at the discretion of the treating physician)

• Concurrent availability of whole blood or blood component therapy

Exclusion Criteria:

• More than 4 hours from trauma to hospital admission

• More than 2 hours from hospital admission to randomization

• Transfusion of more than one packed red blood cell unit prior to randomization.

• Patients who have undergone surgery (laparotomy, thoracotomy, or sternotomy) before hospital admission.

• In-extremis patients with devastating injuries (expected to die within 60 minutes).

• Blood group other than to O or A and positive Rh factor

• Severe traumatic brain injury in which neurosurgical intervention is futile (partial decapitation, massive intracranial hemorrhage, or transcranial gunshot wounds).

• Burns over 20% of the total body surface area.

• Suspected airway burn.

• Cardiopulmonary resuscitation (CPR) before arrival at the ED.

• CPR for more than 5 minutes before randomization.

• Do not resuscitate order.

• Incarcerated/prisoners.

• Known pregnancy in the ED.

• Patient or legal representative who refuse to participate in clinical research studies.

Related Conditions & MeSH terms

• Multiple Trauma
• Trauma
• Trauma Injury
• Trauma, Multiple
• Wounds and Injuries

Intervention

Biological:
• Transfusion of blood products
The intervention will be either a) administration of 6 units of whole blood or b) administration of blood component therapy in the proportion of 6:6:6 units of red blood cells, plasma, and platelets.

Locations

Country	Name	City	State
Colombia	Fundacion Clinica Valle del Lili	Cali	Valle Del Cauca

Sponsors (3)

Lead Sponsor	Collaborator
Fundacion Clinica Valle del Lili	Hospital Universitario del Valle Evaristo Garcia, University of Pittsburgh

Country where clinical trial is conducted

Colombia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome is a hierarchical outcome consisting of mortality at 28 days post-randomization and evolution of organ dysfunction (difference of Sequential Organ Failure Assessment (SOFA) score between day 1 and day 5 post-randomization).	The primary outcome is a hierarchical composite outcome that will be analyzed using the Win-Ratio test. The first level will be 28-day mortality. The "winner" will be the participant who survival; in case of a tie, the second level will be the difference in SOFA score between fifth and first day. The "winner" will be participant with the lowest difference.	28 days post ED admission
Secondary	24-hour mortality	The occurrence of deaths in the first 24 hours post-ED admission and we will document and record the time of death in hours.	First 24 hours post ED admission.
Secondary	In-hospital mortality	The occurrence of deaths during the hospital stays post-ED admission, and we will document and record the time of death in days.	28 days post ED admission
Secondary	Multiple organ dysfunction incidence	Multiple organ dysfunction is a score = 3 in two or more systems evaluated by SOFA score.	1-day / 3-day / 5-day / 7-day post-ED admission
Secondary	Evolution of Coagulopathy	We will evaluate the values of INR, fibrinogen, and MA-TEG during the admission and the first 24 hours post-ED admission.	Admission - 3 hours - 6 hours - 24 hours post-ED admission
Secondary	Intensive care unit-free days	ICU-free days	28-days post-ED admission
Secondary	Hospital length stay-free days	Hospital length stay-free days	28-days post-ED admission
Secondary	Blood transfusion requirements during the first 24 hours	The number of units of whole blood or blood components transfused. Comparisons will be according to the following references: 1 Unit of Whole blood = 1 Unit of packed red blood cells.; 1 Unit of Whole Blood = 1 Unit of Plasma; 1 Unit of Whole Blood = 1 Unit of Platelets	Time frame 3 hours / 6 hours / 12 hours / 24 hours
Secondary	Proportion of participants with transfusional adverse reactions	We will document transfusional adverse reactions such as acute hemolytic reaction, anaphylaxis, non-hemolytic febrile transfusion reaction, allergy, and potassium and calcium electrolyte disorders.	28-days post-ED admission
Secondary	Proportion of participants with adverse reactions	We will document adverse reactions such as acute lung injury, acute respiratory distress syndrome, pulmonary embolism, deep vein thrombosis, acute kidney injury with or without dialysis, stroke, myocardial infarction, cardiac arrest, sepsis, abdominal complications, and abdominal compartment syndrome	28-days post-ED admission