Effect of Leukoreduced Blood Transfusions on Infection Following Trauma

Wounds and Injuries Clinical Trial

Official title:

Effect of Leukoreduction in Infection Risk in Trauma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00135291
• Other study ID #: 02-2517-D02
• Secondary ID: P50HL073996-01
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: August 23, 2005
• Last updated: January 2, 2008
• Start date: February 2003
• Est. completion date: September 2004

Study information

• Verified date: January 2008
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if leukoreduced blood transfusions reduce the risk of infection following trauma. Specifically, the investigators intend to evaluate whether there are clinically relevant differences in the rates of infection and in the severity of multiple organ failure in critically injured trauma patients receiving leukoreduced blood products compared to those receiving standard allogeneic blood products.

Description:

Many severely injured patients survive their initial resuscitation only to suffer the late sequelae of nosocomial infection and multiple organ failure. The depth of hemorrhagic shock and the severity of anatomic injury are clearly associated with these adverse outcomes, however there is clear evidence to suggest that events during the resuscitation phase also play an important role in the pathogenesis of these sequelae. Specifically, there is now substantial clinical and experimental evidence implicating blood transfusion and the transfusion of allogeneic passenger leukocytes in the immune dysregulation characteristic of the post-injury state. This immune dysregulation manifests on two fronts: an uncontrolled inflammatory response leading to organ dysfunction and a state of immunoparalysis, leading to the development of nosocomial infection. Allogeneic passenger leukocytes have been implicated in the alterations in non-specific and specific immunity that underlie this state of altered immunoresponsiveness. The importance of allogeneic leukocytes in these phenomena suggests that strategies designed to limit the exposure of patients to these cells may reduce the incidence of post-injury sequelae. Pre-storage leukoreduction, whereby donated blood is passed through a leukocyte filter prior to storage and ultimate transfusion is one such strategy. This strategy remains at the center of a national debate on a policy of universal leukoreduction in which its efficacy is unproven and its cost undisputed.

Study Objectives:

• To evaluate whether there are clinically relevant differences in the rates of infection and in the severity of multiple organ failure in critically injured trauma patients receiving leukoreduced blood products compared to those receiving standard allogeneic blood products.

• To assess T-cell responsiveness and the dominant CD4 lymphocyte subset as measured by T-lymphocyte IL-2 receptor expression and cytokine profile, respectively, in critically injured subjects transfused with leukoreduced blood products compared to subjects receiving standard allogeneic blood products.

• To assess the activational state of the peripheral blood monocyte and the neutrophil in critically injured trauma patients receiving leukoreduced blood products compared to subjects receiving standard allogeneic blood products.

• To evaluate whether there are clinically relevant differences in rates of acute lung injury (ALI) and circulating markers of ALI in patients receiving leukoreduced versus standard allogeneic blood products.

• To evaluate rates of microchimerism in those receiving leukoreduced versus standard allogeneic transfusion

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. completion date: September 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Trauma patients

• Age > 17

• Transfusion within 24 hours of injury

Exclusion Criteria:

• Active infection at time of injury

• Anticipated survival of < 48 hours (e.g. gunshot wound [GSW] to head, cardiopulmonary resuscitation [CPR] in progress)

• Receipt of blood products for this injury event prior to randomization

• AB negative; B negative blood type.

• Positive antibody screen

• Prior requirement for irradiated, leukoreduced or cytomegalovirus (CMV) seronegative blood products

• Incarcerated

• Enrolled in pre-hospital trial

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Wounds and Injuries

Intervention

Procedure:
• Leukoreduced blood transfusion

Locations

Country	Name	City	State
United States	Harborview Medical Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Nathens AB, Nester TA, Rubenfeld GD, Nirula R, Gernsheimer TB. The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial. Shock. 2006 Oct;26(4):342-7. — View Citation

Utter GH, Nathens AB, Lee TH, Reed WF, Owings JT, Nester TA, Busch MP. Leukoreduction of blood transfusions does not diminish transfusion-associated microchimerism in trauma patients. Transfusion. 2006 Nov;46(11):1863-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infection within 30 days of injury		30 d
Secondary	Marshall organ dysfunction scores over the course of Intensive Care Unit (ICU) admission
Secondary	Hospital length of stay
Secondary	Duration of mechanical ventilation
Secondary	Duration of ICU stay
Secondary	Acute lung injury
Secondary	Plasma circulating levels of inflammatory cytokines and markers of lung injury (days 2-3 and 6-8)
Secondary	Measures of monocyte activation (days 2-3 and 6-8)
Secondary	Measures of polymorphonuclear neutrophil (PMN) activation (days 2-3 and 6-8)
Secondary	Peripheral blood mononuclear cell expression of interleukin-2 (IL-2) receptors (days 2-3 and 6-8)