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Immunomodulation Following Transfusion

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00810810
First Posted: December 18, 2008
Last Update Posted: November 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Bloodworks (Puget Sound Blood Center)
Information provided by (Responsible Party):
Karen Nelson, University of Washington
  Purpose

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.


Condition Intervention Phase
Blood Component Transfusion Biological: Standard blood components Biological: Leukoreduced blood components Biological: Leukoreduced and irradiated Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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.
Masking: Double (Investigator, Outcomes Assessor)
Masking Description:
Clinical teams caring for patients were not masked. Laboratory personnel were masked until all testing completed.
Primary Purpose: Prevention
Official Title: Immunomodulation Following Transfusion

Resource links provided by NLM:


Further study details as provided by Karen Nelson, University of Washington:

Primary Outcome Measures:
  • Production, de Novo, of Antibody to HLA Antigens [ Time Frame: 0 to 5 weeks after surgery ]
    Blood samples were collected prior to surgery and at two times after surgery. Serum was tested for the presence of IgG antibody to HLA. the results of the samples collected after surgery were compared to those in the smaple collected prior to surgery.


Secondary Outcome Measures:
  • Changes in Number or Cytokine Profile of CD4 T Regulatory Cells or NKT Cells. Changes in Numbers of Cells Producing TGFB1. Changes in Secretion of Cytokines [ Time Frame: 0 to 5 weeks after surgery ]
    Blood samples were collected prior to surgery and at two times after surgery. White blood cells were isolated and frozen. The thawed cells were tested for the numbers and phenotype of regulatory cells and for the production of regulatory cytokines. Results obtained from samples collected after surgery were compared to the results obtained from the sample collected prior to surgery.


Enrollment: 287
Study Start Date: July 2006
Study Completion Date: August 2011
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Blood components with no additional treatment
Biological: Standard blood components
Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets
Experimental: 2
Blood components leukoreduced
Biological: Leukoreduced blood components
Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets
Experimental: 3
Blood components leukoreduced and irradiated
Biological: Leukoreduced and irradiated
Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets

Detailed Description:

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00810810


Locations
United States, Washington
Northwest Hospital
Seattle, Washington, United States, 98133
University of Washington Medical Center
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
National Heart, Lung, and Blood Institute (NHLBI)
Bloodworks (Puget Sound Blood Center)
Investigators
Principal Investigator: Karen Nelson, PhD Bloodworks (Puget Sound Blood Center)
Principal Investigator: Gabriel Aldea, MD University of Washington
  More Information

Responsible Party: Karen Nelson, Director, University of Washington
ClinicalTrials.gov Identifier: NCT00810810     History of Changes
Other Study ID Numbers: 29792
1P50HL081015 ( U.S. NIH Grant/Contract )
First Submitted: December 17, 2008
First Posted: December 18, 2008
Results First Submitted: October 26, 2017
Results First Posted: November 29, 2017
Last Update Posted: November 29, 2017
Last Verified: October 2017

Keywords provided by Karen Nelson, University of Washington:
Blood Component Transfusion
Leukoreduction
HLA antibody
Immunosuppression