Immunomodulation Following Transfusion

NCT ID: NCT00810810

Last Updated: 2017-12-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

287 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-07-31

Study Completion Date

2011-08-31

Brief Summary

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This study is designed to provide information on patients' immune response after exposure to transfused blood.

Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of these effects in patients who are not on chemotherapy is unknown.

These effects are thought to be due largely to white blood cells present in the transfusion product. "Leukofiltration" and "gamma-irradiation" are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively.

In this study, patients scheduled for cardiac surgery are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery.

Studies will measure changes in antibody to HLA and in cells that regulate the immune response. The levels of sensitization and immunosuppression will be correlated to the transfusion products received.

Detailed Description

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Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of this problem in patients who are not on chemotherapy is unknown.

Of patients who do receive donor blood, 50-90 percent become sensitized (make antibody) to HLA proteins present on white blood cells in the donor blood. This is an undesired effect in patients who need an organ or stem cell transplant, as it increases the risk of rejection. Another effect of receiving a blood transfusion, immunosuppression, causes a decreased immune response that compromises patients' ability to fight off infection or tumor cells.

These effects - sensitization and immunosuppression - are thought to be due largely to white blood cells present in the transfusion product. Doctors order specially pretreated blood transfusions that have been depleted of white blood cells with the aim of minimizing risks in an "immunocompromised" patient. "Leukofiltration" and "gamma-irradiation" are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively. Therefore, blood is pretreated both ways before it is given to patients who need a stem cell transplant or others who are immunosuppressed.

Sometimes the pretreated leukofiltration and gamma-irradiated blood is used for "regular" patients who are not immunocompromised so the blood is used before it expires and not wasted. However, doctors do not know for sure whether these expensive pretreatments are really beneficial for "regular" patients such as those undergoing cardiac surgery and whether they would change the risk of developing sensitization or immunosuppression.

In this study, patients are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery. Studies will measure changes in antibody to HLA and in cells that regulate the immune response.

It is unknown which treatment (leukofiltration with or without gamma-irradiation compared to no pretreatment) is most beneficial in patients who are not immunosuppressed.

This study is designed to provide information on patients' immune response after exposure to transfused blood. This information may be useful to caring for patients in the future who require transfusion for cardiac surgery.

Conditions

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Blood Component Transfusion

Keywords

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Blood Component Transfusion Leukoreduction HLA antibody Immunosuppression

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Individuals who consented for study were scheduled for cardiac surgery. They were randomized to one of three arms to receive blood components prepared by different, but clinically acceptable processes. If they required transfusion from 2 days prior to surgery until 30 days post surgery they received study product. Blood samples were collected prior to surgery and at two points after surgery.
Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
Clinical teams caring for patients were not masked. Laboratory personnel were masked until all testing completed.

Study Groups

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1

Blood components with no additional treatment

Group Type ACTIVE_COMPARATOR

Standard blood components

Intervention Type BIOLOGICAL

Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets

2

Blood components leukoreduced

Group Type EXPERIMENTAL

Leukoreduced blood components

Intervention Type BIOLOGICAL

Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets

3

Blood components leukoreduced and irradiated

Group Type EXPERIMENTAL

Leukoreduced and irradiated

Intervention Type BIOLOGICAL

Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets

Interventions

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Standard blood components

Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets

Intervention Type BIOLOGICAL

Leukoreduced blood components

Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets

Intervention Type BIOLOGICAL

Leukoreduced and irradiated

Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* At least 18 year of age
* Scheduled for open heart surgery of cardiopulmonary bypass that involves: CABG, CABG with valve, aneurysm repair
* Urgent or elective surgery

Exclusion Criteria

* Scheduled for open heart surgery of cardiopulmonary bypass that involves: placement of a ventricular assist device, cardiac transplantation, aortic dissection repair
* Emergent surgery
* participation in other clinical research studies within 30 days of randomization.
* Immunosuppressive treatment.
* Refuse blood transfusion
* Disease or condition placing subject at undue risk or decision of attending doctor.
* Condition requiring high volume transfusion therapy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Bloodworks

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Karen Nelson

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Karen Nelson, PhD

Role: PRINCIPAL_INVESTIGATOR

Bloodworks

Gabriel Aldea, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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Northwest Hospital

Seattle, Washington, United States

Site Status

University of Washington Medical Center

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Nelson KA, Aldea GS, Warner P, Latchman Y, Gunasekera D, Tamir A, Gernsheimer T, Bolgiano D, Slichter SJ. Transfusion-related immunomodulation: gamma irradiation alters the effects of leukoreduction on alloimmunization. Transfusion. 2019 Nov;59(11):3396-3404. doi: 10.1111/trf.15555. Epub 2019 Oct 13.

Reference Type DERIVED
PMID: 31608454 (View on PubMed)

Other Identifiers

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1P50HL081015

Identifier Type: NIH

Identifier Source: secondary_id

View Link

29792

Identifier Type: -

Identifier Source: org_study_id